BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL)is a common subtype of peripheral T-cell lymphoma.Approximately half of patients with AITL may concurrently present with hypergammaglobulinemia.Increased numbers of p...BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL)is a common subtype of peripheral T-cell lymphoma.Approximately half of patients with AITL may concurrently present with hypergammaglobulinemia.Increased numbers of plasma cells in the bone marrow are commonly observed at diagnosis.These tumors mimic plasma cell myelomas,hindering a conundrum of clinical diagnoses and potentially delaying appropriate treatment.CASE SUMMARY A 78-year-old woman experienced poor appetite,weight loss of 5 kg,fatigue 2 months before presentation,and shortness of breath 2 d before presentation,but no fever or night sweats.Physical examination revealed splenomegaly and many palpable masses over the bilateral axillary regions,approximately>2 cm in size,with rubbery consistency and no tenderness.Blood tests revealed anemia and thrombocytopenia,lactate dehydrogenase level of 153 U/L,total protein level of 10.9 g/dL,albumin to globulin ratio of 0.2,and immunoglobulin G level more than the upper limit of 3000 mg/dL.The free kappa and lambda light chain concentrations were 451 and 614 mg/L,respectively.A pathological examination confirmed the diagnosis of AITL.The initial treatment was the cyclophosphamide,epirubicin,vincristine,and prednisolone regimen.Following this treatment,pleural effusion was controlled,and the patient was discharged in a stable condition and followed up in our outpatient department.CONCLUSION This report highlights the importance of differentiating reactive plasmacytosis from plasma cell myeloma in patients with hypergammaglobulinemia.A precise diagnosis of AITL requires a comprehensive evaluation,involving clinical,immunophenotypic,and histological findings conducted by a multidisciplinary team to ensure appropriate treatment.展开更多
Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations th...Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.展开更多
Objective: Australia has relatively high multiple myeloma(MM) incidence and mortality rates. Advancements in MM treatment over recent decades have driven improvements in MM survival in high-income countries;however, r...Objective: Australia has relatively high multiple myeloma(MM) incidence and mortality rates. Advancements in MM treatment over recent decades have driven improvements in MM survival in high-income countries;however, reporting in Australia is limited. We investigated temporal trends in population-wide MM survival across 3 periods of treatment advancements in New South Wales(NSW), Australia.Methods: Individuals with an MM diagnosis in the NSW Cancer Registry between 1985 and 2015 with vital follow-up to 2020, were categorized into 3 previously defined treatment eras according to their diagnosis date(1985±1995, chemotherapy only;1996±2007, autologous stem cell transplantation;and 2008±2015, novel agents including proteasome inhibitors and immunomodulatory drugs). Both relative survival and cause-specific survival according to Fine and Gray's competing risks cumulative incidence function were calculated by treatment era and age at diagnosis.Results: Overall, 11,591 individuals were included in the study, with a median age of 70 years at diagnosis. Five-year relative survival improved over the 36-year(1985±2020) study period(31.0% in 1985±1995;41.9% in 1996±2007;and 56.1% in 2008±2015). For individuals diagnosed before 70 years of age, the 5-year relative survival nearly doubled, from 36.5% in 1985±1995 to 68.5% in 2008±2015. Improvements for those > 70 years of age were less pronounced between 1985±1995 and 1996±2007;however, significant improvements were observed for those diagnosed in 2008±2015. Similar overall and age-specific patterns were observed for causespecific survival. After adjustment for gender and age at diagnosis, treatment era was strongly associated with both relative and cause-specific survival(P < 0.0001).Conclusions: Survival of individuals with MM is improving in Australia with treatment advances. However, older age groups continue to experience poor survival outcomes with only modest improvements over time. Given the increasing prevalence of MM in Australia, the effects of MM treatment on quality of life, particularly in older age, warrant further attention.展开更多
Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four R...Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated genes.Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM patients.To comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression analysis.The ARRS model emerged as an independent prognostic factor for predicting OS.Furthermore,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling pathway.Nevertheless,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this resistance.In vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs.By employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and fibronectin.This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM.Additionally,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such resistance.These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.展开更多
Multiple myeloma(MM)is a plasma cell malignancy and remains incurable as it lacks effective curative approaches;thus,novel therapeutic strategies are desperately needed.The study aimed to explore the therapeutic role ...Multiple myeloma(MM)is a plasma cell malignancy and remains incurable as it lacks effective curative approaches;thus,novel therapeutic strategies are desperately needed.The study aimed to explore the therapeutic role of dihydromyricetin(DHM)in MM and explore its mechanisms.Human MM and normal plasma samples,human MM cell lines,and normal plasma cells were used for in vitro experiments.Cell counting kit-8(CCK-8),flow cytometry,and trans-well assays were performed for the assessment of cell viability,apoptosis,migration,and invasion,respectively.Quantitative real-time polymerase chain reaction(qRT-PCR)was employed to assess the mRNA expression of signal transducer and activator of transcription 1(STAT1)and retinoic acid-inducible gene I(RIG-I).Western blotting was employed to assess E-cadherin,N-cadherin,signal transducer,STAT1,p-STAT1,and RIG-I protein expression.A tumor xenograft model was used for in vivo experiments.Here,dihydromyricetin(DHM)dose-dependently restrained viability,apoptosis,migration,and invasion,and facilitated apoptosis of U266 cells.After DHM treatment,the Ecadherin level was increased and the N-cadherin level was decreased in U266 and RPMI-8226 cells,suggesting the inhibitory effects of DHM on epithelial-mesenchymal transition(EMT)in MM.Besides,the levels of p-STAT1/STAT1 and RIG-I were down-regulated in MM.However,the STAT1 inhibitor fludarabine undid the suppressive effect of DMH on the malignant characteristics of U266 cells.Also,DHM inhibited MM tumor growth and EMT,and activated STAT1/RIG-I pathway in vivo.Collectively,this study first revealed that DHM can restrain EMT and tumor growth in MM by activating STAT1/RIG-I signaling,which provides a novel drug for the treatment of MM.展开更多
Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug r...Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.展开更多
Background:Bortezomib results in peripheral neuropathy(PN)in approximately 50%of patients,during multiple myeloma(MM)treatment,a complication known as Bortezomib-induced peripheral neuropathy(BIPN).The drug response v...Background:Bortezomib results in peripheral neuropathy(PN)in approximately 50%of patients,during multiple myeloma(MM)treatment,a complication known as Bortezomib-induced peripheral neuropathy(BIPN).The drug response varies among individuals.Genetic factor may play an important role in BIPN.Methods:A nextgeneration sequencing(NGS)panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib therapy.mRNA expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR(RT-qPCR).Serum homocysteine(Hcy)levels were detected in 40 samples by chemiluminescent microparticle immunoassay(CMIA).Results:Compared with the non-BIPN group(n=89),a total of 8 significantly associated single nucleotide polymorphisms(SNPs)were identified in the BIPN group(n=115):MTHFR(rs1801131,rs1801133,rs17421511),EPHX1(rs1051740),MME(rs2016848),ALDH1A1(rs6151031),HTR7(rs1935349)and CYP2A6(rs8192720).The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment(NP group)was lower than that of newly diagnosed patients without peripheral neuritis after treatment(NnP group)(1.70±0.77 vs.2.81±0.97,p=0.009).Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group(11.66±1.79μmol/L vs.8.52±3.29μmol/L,p=0.016)and healthy controls(11.66±1.79μmol/L vs.8.55±2.13μmol/L,p≤0.001).Conclusion:CYP2A6,EPHX1,MTHFR,ALDH1A1,HTR7,MME and BIPN are linked in Chinese MM patients.BIPN is more likely to occur in patients with lower MTHFR mRNA expression,which might result in higher serum Hcy levels.展开更多
Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complication...Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complications of MM are available. We aim to describe the microbiological features of infections in MM, and their impact on survival in Senegalese patients. Methods: A retrospective (January 2005-January 2022), analytic, multicenter study on infections in patients followed for MM (IMWG criteria) in Senegalese clinical hematology services. The socio-epidemiological, diagnostic, microbiological, evolutionary and survival aspects were analyzed. Results: The study included 106 patients with multiple myeloma who had an infection at admission or during the treatment. Ten patients have the comorbidity (hypertension, lupus, type 2 diabetes). These patients had 136 infectious events identified at diagnosis (79.2%) or during chemotherapy (20.8%). The sites of infection are lung (42.6%), urinary (29.4%), dermatological (6.6%), digestive (5.2%), osteoarticular (4.4%), ear, nose and throat (3.7%), central nervous system (1.5%), or without site. We recorded 26.4% of patients with multi-site infections. The causal pathogens are bacteria (Gram-negative bacilli: 22.1%;Gram positive bacilli: 9.5%, Mycobacterium tuberculosis: 13.3%), parasitique (plasmodium falciparum 6.6%), viruses (SARS-COV2: 2.9%, VZV: 2.2%) and fungal (2.9%). Survival was reduced in patients who had an infection at the time of multiple myeloma diagnosis (p: 0.189) and those who had multiple infectious foci (p: 0.011). Conclusion: Infections in multiple myeloma are more frequent at diagnosis. The germs are varied and mostly bacteria, particularly gram-negative bacteria, and Kochs bacillus. Our study reveals that multiple infectious foci are a poor prognosis factor. It is necessary to evaluate the infectious risk early, and to adopt an antibiotic prophylaxis based on our tropical environment.展开更多
BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.Th...BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.展开更多
Objective:To analyze the effect of bortezomib combined with dexamethasone and lenalidomide in the treatment of multiple myeloma.Methods:60 cases of multiple myeloma patients admitted to our hospital from January 2022 ...Objective:To analyze the effect of bortezomib combined with dexamethasone and lenalidomide in the treatment of multiple myeloma.Methods:60 cases of multiple myeloma patients admitted to our hospital from January 2022 to December 2023 were selected randomly,with 30 cases in each group.Bortezomib combined with dexamethasone was administered in the control group,and bortezomib combined with dexamethasone and lenalidomide was given to the observation group,and the treatment effect was analyzed.Results:After treatment,CD^(3+)and CD^(4+)of the observation group were higher than that of the control group,CD^(8+)was lower than that of the control group,and the total treatment efficiency was higher,which was statistically significant(P<0.05),and there was no difference in the total incidence of adverse reactions between the two groups(P>0.05).Conclusion:Bortezomib combined with dexamethasone and lenalidomide is effective in the treatment of multiple myeloma as it regulates the immune function and is safe,thus it can be promoted in clinical practice.展开更多
Multiple myeloma(MM) is the second most common hematologic malignancy, and is characterized by the clonal expansion of malignant plasma cells. Despite the recent improvement in patient outcome due to the use of novel ...Multiple myeloma(MM) is the second most common hematologic malignancy, and is characterized by the clonal expansion of malignant plasma cells. Despite the recent improvement in patient outcome due to the use of novel therapeutic agents and stem cell transplantation, all patients eventually relapse due to clone evolution. B cell maturation antigen(BCMA) is highly expressed in and specific for MM cells, and has been implicated in the pathogenesis as well as treatment development for MM. In this review, we will summarize representative anti-BCMA immune therapeutic strategies, including BCMA-targeted vaccines, anti-BCMA antibodies and BCMA-targeted CAR cells. Combination of different immunotherapeutic strategies of targeting BCMA, multi-target immune therapeutic strategies, and adding immune modulatory agents to normalize anti-MM immune system in minimal residual disease(MRD) negative patients, will also be discussed.展开更多
We describe a patient with concomitant B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). CLL- and MM-cell were separated by preparative flourescence-activated cell sorting (FACS). DNA sequence analy...We describe a patient with concomitant B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). CLL- and MM-cell were separated by preparative flourescence-activated cell sorting (FACS). DNA sequence analysis of the complementarity-determinining region III (CDR III) of the immunoglobulin heavy chain genes showed identical gene rearrangements in the CLL- and the MM-cell population. Our findings prove a common clonal tumor origin of both B-cell diseases in this patient.展开更多
Multiple myeloma(MM)is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow(BM).The interaction between MM cells and the BM microenvironment,a...Multiple myeloma(MM)is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow(BM).The interaction between MM cells and the BM microenvironment,and specifically BM mesenchymal stem cells(BM-MSCs),has a key role in the pathophysiology of this disease.Multiple data support the idea that BM-MSCs not only enhance the proliferation and survival of MM cells but are also involved in the resistance of MM cells to certain drugs,aiding the progression of this hematological tumor.The relation of MM cells with the resident BM-MSCs is a two-way interaction.MM modulate the behavior of BM-MSCs altering their expression profile,proliferation rate,osteogenic potential,and expression of senescence markers.In turn,modified BM-MSCs can produce a set of cytokines that would modulate the BM microenvironment to favor disease progression.The interaction between MM cells and BM-MSCs can be mediated by the secretion of a variety of soluble factors and extracellular vesicles carrying microRNAs,long non-coding RNAs or other molecules.However,the communication between these two types of cells could also involve a direct physical interaction through adhesion molecules or tunneling nanotubes.Thus,understanding the way this communication works and developing strategies to interfere in the process,would preclude the expansion of the MM cells and might offer alternative treatments for this incurable disease.展开更多
Multiple myeloma(MM)is a heterogeneous disease of the hematological system,characterized by different subtypes and different prognosis.Age,tumor burden,biological characteristics and treatment response can affect the ...Multiple myeloma(MM)is a heterogeneous disease of the hematological system,characterized by different subtypes and different prognosis.Age,tumor burden,biological characteristics and treatment response can affect the prognosis.MM cells accumulate in bone marrow and produce abnormal immunoglobulin.Abnormal immunoglobulin does not participate in immune response and inhibits adaptive immune system is the most significant pathophysiological characteristics of MM.Hyperviscosity,amyloidosis,infection and kidney injury are the important complications of MM.This paper analyzes the traditional Chinese medicine(TCM)understanding of these important complications,and summarizes the commonly used clinical Chinese medicine,in order to provide important basis for the TCM treatment of multiple myeloma.展开更多
Thirty-one multiple myeloma patients were classified chiefly by heavy and light chain detec-tion of myeloma protein (M protein).The results were as follows:19 out of the 31 casesbelonged to the IgG class,including the...Thirty-one multiple myeloma patients were classified chiefly by heavy and light chain detec-tion of myeloma protein (M protein).The results were as follows:19 out of the 31 casesbelonged to the IgG class,including the following subclasses—IgG1-λ.7;IgG1-k.5;IgG3-λ,1;IgG3-k,2;double M myeoma,2 (IgG3-λ+IgG2-k,IgG1-λ+IgG4-λ);IgG-λ,1;andIgG1-k 1.Seven cases were light chain diseases,of which 4 belonged to λ type.2 were k.and one was a double light chain disease.Five cases belonged to the IgA class (IgA-λ,3;IgA-k,2).We found no correlation between electrophoretic mobility and the antigenicity ofM protein even within subclasses,and the highly concentrated BJP in urine had a tendencyto form light chain polymers,possibly along different polymerization pathways.展开更多
Objective:To investigate the effects of Bortezomib and Dexamethasone combination on treating senile multiple myeloma and influence on immune suppressed factors and immune cell levels.Methods:A total of 80 cases of pat...Objective:To investigate the effects of Bortezomib and Dexamethasone combination on treating senile multiple myeloma and influence on immune suppressed factors and immune cell levels.Methods:A total of 80 cases of patients with multiple myeloma treated in our hospital from Oct 2013 to Jul 2015 were selected as investigate subjects. They were randomly divided to be observation group consisted of 43 cases and control group consisted of 37 cases. For observation group, treatment of Bortezomib and Dexamethasone combination was provided. For control group, Vincristine + Epirubicin + Dexamethasone treatment was provided. After three courses, effects on two groups of patients were compared, and immune suppressed factors and immune cell levels before and after treatment in different periods were compared.Results:After three courses of treatment, the total effective rate in observation group was significantly higher than control group. Before treatment, IL-6, IL-17, TGF-β, CD3+CD4+, CD3+CD8+ and CD3+CD4+/CD3+CD8+ between the two group of patients were compared, no significant difference showed;After treatment for 6 weeks, IL-6, IL-17 levels in observation group were significantly decreased comparing with the same group before treatment;After treatment for 12 weeks, IL-6, IL-17 and TGF-β levels in observation group were significantly decreased comparing with the same group before treatment;After treatment, IL-6, IL-17 levels in observation group were significantly lower than control group at the same phase. After treatment for 12 weeks, CD3+CD4+, CD3+CD4+/CD3+CD8+ in observation group were significantly higher than the same group before treatment, and significantly higher than control group at the same phase;CD3+CD8+ in observation group was significantly lower than the same group before treatment, and significantly lower than control group at the same phase. Conclusion:Compared with Vincristine + Epirubicin + Dexamethasone treatment, Bortezomib and Dexamethasone combination on treating senile multiple myeloma had more significant effects, which deserves further clinical researches.展开更多
BACKGROUND Immunoglobulin D(IgD)multiple myeloma(MM)is a rare subtype of MM and commonly occurs in younger subjects but at a later stage of the International Staging System(ISS)when admitted.As a special type of IgD m...BACKGROUND Immunoglobulin D(IgD)multiple myeloma(MM)is a rare subtype of MM and commonly occurs in younger subjects but at a later stage of the International Staging System(ISS)when admitted.As a special type of IgD myeloma,IgD-λ/λbiclonal MM is rarer.Its serum protein electrophoresis and serum immunofixation electrophoresis(IFE)might find no anomalies even if the bone marrow(BM)examination is performed.Thus,it is easy to miss the diagnosis.CASE SUMMARY A 62-year-old man diagnosed as IgD-λ/λmyeloma(ISS stage III)was admitted with fatigue and weight loss.The physical examination suggested an anemic face,a few moist rales at the left lung base,and mild concave edema in both lower extremities.Laboratory examinations showed the elevated creatinine levels,β2-microglobulin,lactic dehydrogenase,and erythrocyte sedimentation rate,while the decreased neutrophils,granulocytes,and hemoglobin.In the serum protein electrophoresis,there appeared two inconspicuous M-spikes.Serum IFE indicated an over-representation of lambda light chain and yielded two monoclonal bands inλregion,but only one corresponding heavy chain band in the antisera to IgD region.The BM histology and BM cytology both supported the diagnosis of IgD-λ/λmyeloma.CONCLUSION This case highlights the differential clinical manifestations and laboratory findings of IgD-λ/λmyeloma to help minimize the chance of misdiagnosis.展开更多
Summary Existence of a graft-versus-myeloma effect has been well documented by responses to donor lymphocyte infusions and long-term survival after allogeneic bone marrow transplantation. The development of non-myeloa...Summary Existence of a graft-versus-myeloma effect has been well documented by responses to donor lymphocyte infusions and long-term survival after allogeneic bone marrow transplantation. The development of non-myeloablative conditioning regimens allows utilization of allogeneic effects in patients usually not suitable for myeloablative allogeneic transplantation, such as older and heavily pretreated patients. In a small series of 11 patients with multiple myeloma relapsing after autologous transplantation, we show that conditioning with low-dose total body irradiation in combination with fludarabine allows stable engraftment after matched unrelated donor transplantation and is tolerated with acceptable transplant-related morbidity and mortality. With a short median follow-up of 225 days, disease control was achieved only for patients responding to conventional treatment prior to allografting. Future studies with longer follow-up have to define the role of non-myeloablative allogeneic transplantation from unrelated donors as consolidation for patients responding to salvage therapy.展开更多
Objective:In this study, the effects of bortezomib and vincristine combined with dexamethasone and thalidomide on immune function, inflammatory response, renal function, myeloma cells and plasma cells in patients with...Objective:In this study, the effects of bortezomib and vincristine combined with dexamethasone and thalidomide on immune function, inflammatory response, renal function, myeloma cells and plasma cells in patients with multiple myeloma were compared.Methods:68 patients with multiple myeloma treated in our hospital from May 2009 to Nov. 2018 were selected and divided into control group and observation group according to the drugs used in chemotherapy. The control group was treated with vincristine combined with dexamethasone and thalidomide, while the observation group was treated with bortezomib combined with dexamethasone and thalidomide. Immunocytes, inflammatory cytokines, serum creatinine, blood urea nitrogen, myeloma cells and plasma cells were detected before and after treatment in the two groups.Results: There was no significant difference in each index between the two groups before treatment (P>0.05). After three courses of chemotherapy, CD3+, CD4+, CD4+/CD8+ and Treg in the observation group were significantly better than those in the control group, and the difference between the two groups was statistically significant (P<0.05). The levels of inflammatory cytokines CRP, TNF-α, myeloma cells and M protein were significantly decreased in the observation group (P<0.05). Renal function indexes in the observation group were significantly higher than those in the control group (P<0.05). There was no significant difference in clinical efficacy and adverse reactions between the two groups (P<0.05).Conclusion: Bortezomib combined with dexamethasone and thalidomide can effectively reduce the inflammatory response, M protein and myeloma cells in patients with MM, significantly improve the immune function and renal function in patients, which has certain clinical application value.展开更多
文摘BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL)is a common subtype of peripheral T-cell lymphoma.Approximately half of patients with AITL may concurrently present with hypergammaglobulinemia.Increased numbers of plasma cells in the bone marrow are commonly observed at diagnosis.These tumors mimic plasma cell myelomas,hindering a conundrum of clinical diagnoses and potentially delaying appropriate treatment.CASE SUMMARY A 78-year-old woman experienced poor appetite,weight loss of 5 kg,fatigue 2 months before presentation,and shortness of breath 2 d before presentation,but no fever or night sweats.Physical examination revealed splenomegaly and many palpable masses over the bilateral axillary regions,approximately>2 cm in size,with rubbery consistency and no tenderness.Blood tests revealed anemia and thrombocytopenia,lactate dehydrogenase level of 153 U/L,total protein level of 10.9 g/dL,albumin to globulin ratio of 0.2,and immunoglobulin G level more than the upper limit of 3000 mg/dL.The free kappa and lambda light chain concentrations were 451 and 614 mg/L,respectively.A pathological examination confirmed the diagnosis of AITL.The initial treatment was the cyclophosphamide,epirubicin,vincristine,and prednisolone regimen.Following this treatment,pleural effusion was controlled,and the patient was discharged in a stable condition and followed up in our outpatient department.CONCLUSION This report highlights the importance of differentiating reactive plasmacytosis from plasma cell myeloma in patients with hypergammaglobulinemia.A precise diagnosis of AITL requires a comprehensive evaluation,involving clinical,immunophenotypic,and histological findings conducted by a multidisciplinary team to ensure appropriate treatment.
基金supported by the National Natural Science Foundation of China(52073145 and 82004081)the Jiangsu Talent Professor Program,Jiangsu Innovation Project of Graduate Student(KYCX23-2192)+1 种基金the National Natural Science Foundation of Nanjing University of Chinese Medicine(NZY82004081)the Special Grants of China Postdoctoral Science Foundation(2021T140792).
文摘Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.
基金part of the Cancer-Patient Population Projections project funded by a Medical Research Future Fund (MRFF) Preventive and Public Health Research Initiative:2019 Target Health System and Community Organisation Research Grant Opportunity (Grant No. MRF1200535)supported by National Health and Research Council of Australia Leadership Investigator Grants (NHMRC+3 种基金Grant No. APP1194679)co-PI of an investigator-initiated trial of cervical screening, “Compass,” run by the Australian Centre for the Prevention of Cervical Cancer (ACPCC),a government-funded not-for-profit charitythe ACPCC has received equipment and a funding contributions from Roche Molecular Diagnostics, USAco-PI on a major implementation program, Elimination of Cervical Cancer in the Western Pacific, which has received support from the Minderoo Foundation。
文摘Objective: Australia has relatively high multiple myeloma(MM) incidence and mortality rates. Advancements in MM treatment over recent decades have driven improvements in MM survival in high-income countries;however, reporting in Australia is limited. We investigated temporal trends in population-wide MM survival across 3 periods of treatment advancements in New South Wales(NSW), Australia.Methods: Individuals with an MM diagnosis in the NSW Cancer Registry between 1985 and 2015 with vital follow-up to 2020, were categorized into 3 previously defined treatment eras according to their diagnosis date(1985±1995, chemotherapy only;1996±2007, autologous stem cell transplantation;and 2008±2015, novel agents including proteasome inhibitors and immunomodulatory drugs). Both relative survival and cause-specific survival according to Fine and Gray's competing risks cumulative incidence function were calculated by treatment era and age at diagnosis.Results: Overall, 11,591 individuals were included in the study, with a median age of 70 years at diagnosis. Five-year relative survival improved over the 36-year(1985±2020) study period(31.0% in 1985±1995;41.9% in 1996±2007;and 56.1% in 2008±2015). For individuals diagnosed before 70 years of age, the 5-year relative survival nearly doubled, from 36.5% in 1985±1995 to 68.5% in 2008±2015. Improvements for those > 70 years of age were less pronounced between 1985±1995 and 1996±2007;however, significant improvements were observed for those diagnosed in 2008±2015. Similar overall and age-specific patterns were observed for causespecific survival. After adjustment for gender and age at diagnosis, treatment era was strongly associated with both relative and cause-specific survival(P < 0.0001).Conclusions: Survival of individuals with MM is improving in Australia with treatment advances. However, older age groups continue to experience poor survival outcomes with only modest improvements over time. Given the increasing prevalence of MM in Australia, the effects of MM treatment on quality of life, particularly in older age, warrant further attention.
基金supported by Incubation Program for Clinical Trials(No.19HXFH030)Achievement Transformation Project(No.CGZH21001)+4 种基金1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYJC21007)Translational Research Grant of NCRCH(No.2021WWB03),Chengdu Science and Technology Program(No.2022-YF05-01444-SN)Key Research and Development Program of Sichuan Province(No.2023YFS0031)Post-Doctor Research Project,West China Hospital,Sichuan University(No.2023HXBH111)National Key Research and Development Program of China(Nos.2022YFC2502600,2022YFC2502603).
文摘Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated genes.Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM patients.To comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression analysis.The ARRS model emerged as an independent prognostic factor for predicting OS.Furthermore,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling pathway.Nevertheless,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this resistance.In vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs.By employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and fibronectin.This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM.Additionally,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such resistance.These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.
基金The authors disclosed receipt of the following financial support for the research,authorship,and/or publication of this article:This work was supported by Mechanism of Dihydromyricetin Inhibiting Multiple Myeloma Growth and Epithelial Mesenchymal Transition by Regulating STAT1/RIG-I Pathway(Grant Number 2022KY094).
文摘Multiple myeloma(MM)is a plasma cell malignancy and remains incurable as it lacks effective curative approaches;thus,novel therapeutic strategies are desperately needed.The study aimed to explore the therapeutic role of dihydromyricetin(DHM)in MM and explore its mechanisms.Human MM and normal plasma samples,human MM cell lines,and normal plasma cells were used for in vitro experiments.Cell counting kit-8(CCK-8),flow cytometry,and trans-well assays were performed for the assessment of cell viability,apoptosis,migration,and invasion,respectively.Quantitative real-time polymerase chain reaction(qRT-PCR)was employed to assess the mRNA expression of signal transducer and activator of transcription 1(STAT1)and retinoic acid-inducible gene I(RIG-I).Western blotting was employed to assess E-cadherin,N-cadherin,signal transducer,STAT1,p-STAT1,and RIG-I protein expression.A tumor xenograft model was used for in vivo experiments.Here,dihydromyricetin(DHM)dose-dependently restrained viability,apoptosis,migration,and invasion,and facilitated apoptosis of U266 cells.After DHM treatment,the Ecadherin level was increased and the N-cadherin level was decreased in U266 and RPMI-8226 cells,suggesting the inhibitory effects of DHM on epithelial-mesenchymal transition(EMT)in MM.Besides,the levels of p-STAT1/STAT1 and RIG-I were down-regulated in MM.However,the STAT1 inhibitor fludarabine undid the suppressive effect of DMH on the malignant characteristics of U266 cells.Also,DHM inhibited MM tumor growth and EMT,and activated STAT1/RIG-I pathway in vivo.Collectively,this study first revealed that DHM can restrain EMT and tumor growth in MM by activating STAT1/RIG-I signaling,which provides a novel drug for the treatment of MM.
基金Research Projects-Joint Fund for Applied Basic Research of Kunming Medical University,Yunnan Provincial Department of Science and Technology(No.2018FE001(-113),No.202301AY070001-098)Open project of Yunnan Clinical Medical Center(Nos.2020LCZXKF-XY02,XY06,XY16+1 种基金2022LCZXKF-XY02)Yunnan Health Training Project of High Level Talents(No.D–2018018).
文摘Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.
基金supported by the“GZ Hematologic Malignancy MARKER GHROMOS of Education Department of Liaoning Province”Grant(Grant Number:07102).
文摘Background:Bortezomib results in peripheral neuropathy(PN)in approximately 50%of patients,during multiple myeloma(MM)treatment,a complication known as Bortezomib-induced peripheral neuropathy(BIPN).The drug response varies among individuals.Genetic factor may play an important role in BIPN.Methods:A nextgeneration sequencing(NGS)panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib therapy.mRNA expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR(RT-qPCR).Serum homocysteine(Hcy)levels were detected in 40 samples by chemiluminescent microparticle immunoassay(CMIA).Results:Compared with the non-BIPN group(n=89),a total of 8 significantly associated single nucleotide polymorphisms(SNPs)were identified in the BIPN group(n=115):MTHFR(rs1801131,rs1801133,rs17421511),EPHX1(rs1051740),MME(rs2016848),ALDH1A1(rs6151031),HTR7(rs1935349)and CYP2A6(rs8192720).The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment(NP group)was lower than that of newly diagnosed patients without peripheral neuritis after treatment(NnP group)(1.70±0.77 vs.2.81±0.97,p=0.009).Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group(11.66±1.79μmol/L vs.8.52±3.29μmol/L,p=0.016)and healthy controls(11.66±1.79μmol/L vs.8.55±2.13μmol/L,p≤0.001).Conclusion:CYP2A6,EPHX1,MTHFR,ALDH1A1,HTR7,MME and BIPN are linked in Chinese MM patients.BIPN is more likely to occur in patients with lower MTHFR mRNA expression,which might result in higher serum Hcy levels.
文摘Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complications of MM are available. We aim to describe the microbiological features of infections in MM, and their impact on survival in Senegalese patients. Methods: A retrospective (January 2005-January 2022), analytic, multicenter study on infections in patients followed for MM (IMWG criteria) in Senegalese clinical hematology services. The socio-epidemiological, diagnostic, microbiological, evolutionary and survival aspects were analyzed. Results: The study included 106 patients with multiple myeloma who had an infection at admission or during the treatment. Ten patients have the comorbidity (hypertension, lupus, type 2 diabetes). These patients had 136 infectious events identified at diagnosis (79.2%) or during chemotherapy (20.8%). The sites of infection are lung (42.6%), urinary (29.4%), dermatological (6.6%), digestive (5.2%), osteoarticular (4.4%), ear, nose and throat (3.7%), central nervous system (1.5%), or without site. We recorded 26.4% of patients with multi-site infections. The causal pathogens are bacteria (Gram-negative bacilli: 22.1%;Gram positive bacilli: 9.5%, Mycobacterium tuberculosis: 13.3%), parasitique (plasmodium falciparum 6.6%), viruses (SARS-COV2: 2.9%, VZV: 2.2%) and fungal (2.9%). Survival was reduced in patients who had an infection at the time of multiple myeloma diagnosis (p: 0.189) and those who had multiple infectious foci (p: 0.011). Conclusion: Infections in multiple myeloma are more frequent at diagnosis. The germs are varied and mostly bacteria, particularly gram-negative bacteria, and Kochs bacillus. Our study reveals that multiple infectious foci are a poor prognosis factor. It is necessary to evaluate the infectious risk early, and to adopt an antibiotic prophylaxis based on our tropical environment.
基金National Key Research and Development Program of China,No.2021YFC2701704the National Clinical Medical Research Center for Geriatric Diseases,"Multicenter RCT"Research Project,No.NCRCG-PLAGH-20230010the Military Logistics Independent Research Project,No.2022HQZZ06.
文摘BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.
基金Shandong Medical Association Clinical Research Specialization(YXH2022ZX03231)。
文摘Objective:To analyze the effect of bortezomib combined with dexamethasone and lenalidomide in the treatment of multiple myeloma.Methods:60 cases of multiple myeloma patients admitted to our hospital from January 2022 to December 2023 were selected randomly,with 30 cases in each group.Bortezomib combined with dexamethasone was administered in the control group,and bortezomib combined with dexamethasone and lenalidomide was given to the observation group,and the treatment effect was analyzed.Results:After treatment,CD^(3+)and CD^(4+)of the observation group were higher than that of the control group,CD^(8+)was lower than that of the control group,and the total treatment efficiency was higher,which was statistically significant(P<0.05),and there was no difference in the total incidence of adverse reactions between the two groups(P>0.05).Conclusion:Bortezomib combined with dexamethasone and lenalidomide is effective in the treatment of multiple myeloma as it regulates the immune function and is safe,thus it can be promoted in clinical practice.
文摘Multiple myeloma(MM) is the second most common hematologic malignancy, and is characterized by the clonal expansion of malignant plasma cells. Despite the recent improvement in patient outcome due to the use of novel therapeutic agents and stem cell transplantation, all patients eventually relapse due to clone evolution. B cell maturation antigen(BCMA) is highly expressed in and specific for MM cells, and has been implicated in the pathogenesis as well as treatment development for MM. In this review, we will summarize representative anti-BCMA immune therapeutic strategies, including BCMA-targeted vaccines, anti-BCMA antibodies and BCMA-targeted CAR cells. Combination of different immunotherapeutic strategies of targeting BCMA, multi-target immune therapeutic strategies, and adding immune modulatory agents to normalize anti-MM immune system in minimal residual disease(MRD) negative patients, will also be discussed.
文摘We describe a patient with concomitant B-cell chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). CLL- and MM-cell were separated by preparative flourescence-activated cell sorting (FACS). DNA sequence analysis of the complementarity-determinining region III (CDR III) of the immunoglobulin heavy chain genes showed identical gene rearrangements in the CLL- and the MM-cell population. Our findings prove a common clonal tumor origin of both B-cell diseases in this patient.
基金Supported by The“Instituto de Salud Carlos III,No.PI22/00264A Predoctoral Program in Biomedicine from The University of Cantabria and The Instituto de Investigación Valdecilla-IDIVAL(Alberto González-González and Daniel García-Sánchez),No.PREVAL19/02,and No.PREVAL20/01“Investigo Program”,part of the“Plan Nacional de Recuperación,Transformación y Resiliencia”from The Spanish Government(Mónica del Dujo-Gutiérrez).
文摘Multiple myeloma(MM)is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow(BM).The interaction between MM cells and the BM microenvironment,and specifically BM mesenchymal stem cells(BM-MSCs),has a key role in the pathophysiology of this disease.Multiple data support the idea that BM-MSCs not only enhance the proliferation and survival of MM cells but are also involved in the resistance of MM cells to certain drugs,aiding the progression of this hematological tumor.The relation of MM cells with the resident BM-MSCs is a two-way interaction.MM modulate the behavior of BM-MSCs altering their expression profile,proliferation rate,osteogenic potential,and expression of senescence markers.In turn,modified BM-MSCs can produce a set of cytokines that would modulate the BM microenvironment to favor disease progression.The interaction between MM cells and BM-MSCs can be mediated by the secretion of a variety of soluble factors and extracellular vesicles carrying microRNAs,long non-coding RNAs or other molecules.However,the communication between these two types of cells could also involve a direct physical interaction through adhesion molecules or tunneling nanotubes.Thus,understanding the way this communication works and developing strategies to interfere in the process,would preclude the expansion of the MM cells and might offer alternative treatments for this incurable disease.
文摘Multiple myeloma(MM)is a heterogeneous disease of the hematological system,characterized by different subtypes and different prognosis.Age,tumor burden,biological characteristics and treatment response can affect the prognosis.MM cells accumulate in bone marrow and produce abnormal immunoglobulin.Abnormal immunoglobulin does not participate in immune response and inhibits adaptive immune system is the most significant pathophysiological characteristics of MM.Hyperviscosity,amyloidosis,infection and kidney injury are the important complications of MM.This paper analyzes the traditional Chinese medicine(TCM)understanding of these important complications,and summarizes the commonly used clinical Chinese medicine,in order to provide important basis for the TCM treatment of multiple myeloma.
文摘Thirty-one multiple myeloma patients were classified chiefly by heavy and light chain detec-tion of myeloma protein (M protein).The results were as follows:19 out of the 31 casesbelonged to the IgG class,including the following subclasses—IgG1-λ.7;IgG1-k.5;IgG3-λ,1;IgG3-k,2;double M myeoma,2 (IgG3-λ+IgG2-k,IgG1-λ+IgG4-λ);IgG-λ,1;andIgG1-k 1.Seven cases were light chain diseases,of which 4 belonged to λ type.2 were k.and one was a double light chain disease.Five cases belonged to the IgA class (IgA-λ,3;IgA-k,2).We found no correlation between electrophoretic mobility and the antigenicity ofM protein even within subclasses,and the highly concentrated BJP in urine had a tendencyto form light chain polymers,possibly along different polymerization pathways.
文摘Objective:To investigate the effects of Bortezomib and Dexamethasone combination on treating senile multiple myeloma and influence on immune suppressed factors and immune cell levels.Methods:A total of 80 cases of patients with multiple myeloma treated in our hospital from Oct 2013 to Jul 2015 were selected as investigate subjects. They were randomly divided to be observation group consisted of 43 cases and control group consisted of 37 cases. For observation group, treatment of Bortezomib and Dexamethasone combination was provided. For control group, Vincristine + Epirubicin + Dexamethasone treatment was provided. After three courses, effects on two groups of patients were compared, and immune suppressed factors and immune cell levels before and after treatment in different periods were compared.Results:After three courses of treatment, the total effective rate in observation group was significantly higher than control group. Before treatment, IL-6, IL-17, TGF-β, CD3+CD4+, CD3+CD8+ and CD3+CD4+/CD3+CD8+ between the two group of patients were compared, no significant difference showed;After treatment for 6 weeks, IL-6, IL-17 levels in observation group were significantly decreased comparing with the same group before treatment;After treatment for 12 weeks, IL-6, IL-17 and TGF-β levels in observation group were significantly decreased comparing with the same group before treatment;After treatment, IL-6, IL-17 levels in observation group were significantly lower than control group at the same phase. After treatment for 12 weeks, CD3+CD4+, CD3+CD4+/CD3+CD8+ in observation group were significantly higher than the same group before treatment, and significantly higher than control group at the same phase;CD3+CD8+ in observation group was significantly lower than the same group before treatment, and significantly lower than control group at the same phase. Conclusion:Compared with Vincristine + Epirubicin + Dexamethasone treatment, Bortezomib and Dexamethasone combination on treating senile multiple myeloma had more significant effects, which deserves further clinical researches.
基金National Natural Science Foundation of China,No.81500430 and No.U1304802Science and Technology Planning Project of Henan Province,No.192102310045,No.182102310544,No.182102310566,and No.182102310573Henan Medical Science and Technology Tackling Project,No.2018020320.
文摘BACKGROUND Immunoglobulin D(IgD)multiple myeloma(MM)is a rare subtype of MM and commonly occurs in younger subjects but at a later stage of the International Staging System(ISS)when admitted.As a special type of IgD myeloma,IgD-λ/λbiclonal MM is rarer.Its serum protein electrophoresis and serum immunofixation electrophoresis(IFE)might find no anomalies even if the bone marrow(BM)examination is performed.Thus,it is easy to miss the diagnosis.CASE SUMMARY A 62-year-old man diagnosed as IgD-λ/λmyeloma(ISS stage III)was admitted with fatigue and weight loss.The physical examination suggested an anemic face,a few moist rales at the left lung base,and mild concave edema in both lower extremities.Laboratory examinations showed the elevated creatinine levels,β2-microglobulin,lactic dehydrogenase,and erythrocyte sedimentation rate,while the decreased neutrophils,granulocytes,and hemoglobin.In the serum protein electrophoresis,there appeared two inconspicuous M-spikes.Serum IFE indicated an over-representation of lambda light chain and yielded two monoclonal bands inλregion,but only one corresponding heavy chain band in the antisera to IgD region.The BM histology and BM cytology both supported the diagnosis of IgD-λ/λmyeloma.CONCLUSION This case highlights the differential clinical manifestations and laboratory findings of IgD-λ/λmyeloma to help minimize the chance of misdiagnosis.
文摘Summary Existence of a graft-versus-myeloma effect has been well documented by responses to donor lymphocyte infusions and long-term survival after allogeneic bone marrow transplantation. The development of non-myeloablative conditioning regimens allows utilization of allogeneic effects in patients usually not suitable for myeloablative allogeneic transplantation, such as older and heavily pretreated patients. In a small series of 11 patients with multiple myeloma relapsing after autologous transplantation, we show that conditioning with low-dose total body irradiation in combination with fludarabine allows stable engraftment after matched unrelated donor transplantation and is tolerated with acceptable transplant-related morbidity and mortality. With a short median follow-up of 225 days, disease control was achieved only for patients responding to conventional treatment prior to allografting. Future studies with longer follow-up have to define the role of non-myeloablative allogeneic transplantation from unrelated donors as consolidation for patients responding to salvage therapy.
文摘Objective:In this study, the effects of bortezomib and vincristine combined with dexamethasone and thalidomide on immune function, inflammatory response, renal function, myeloma cells and plasma cells in patients with multiple myeloma were compared.Methods:68 patients with multiple myeloma treated in our hospital from May 2009 to Nov. 2018 were selected and divided into control group and observation group according to the drugs used in chemotherapy. The control group was treated with vincristine combined with dexamethasone and thalidomide, while the observation group was treated with bortezomib combined with dexamethasone and thalidomide. Immunocytes, inflammatory cytokines, serum creatinine, blood urea nitrogen, myeloma cells and plasma cells were detected before and after treatment in the two groups.Results: There was no significant difference in each index between the two groups before treatment (P>0.05). After three courses of chemotherapy, CD3+, CD4+, CD4+/CD8+ and Treg in the observation group were significantly better than those in the control group, and the difference between the two groups was statistically significant (P<0.05). The levels of inflammatory cytokines CRP, TNF-α, myeloma cells and M protein were significantly decreased in the observation group (P<0.05). Renal function indexes in the observation group were significantly higher than those in the control group (P<0.05). There was no significant difference in clinical efficacy and adverse reactions between the two groups (P<0.05).Conclusion: Bortezomib combined with dexamethasone and thalidomide can effectively reduce the inflammatory response, M protein and myeloma cells in patients with MM, significantly improve the immune function and renal function in patients, which has certain clinical application value.