BACKGROUND Platelet transfusion is of great significance in the treatment of thrombocytopenia caused by myelosuppression during intensive chemotherapy in patients with acute leukemia.In recent years,with platelet tran...BACKGROUND Platelet transfusion is of great significance in the treatment of thrombocytopenia caused by myelosuppression during intensive chemotherapy in patients with acute leukemia.In recent years,with platelet transfusion increasing,ineffective platelet transfusion has become increasingly prominent.Generally speaking,platelet antibodies can be produced after repeated transfusion,thus rendering subsequent platelet transfusion ineffective.We report a case of first platelet transfusion refractoriness(PTR)in a patient with acute myelocytic leukemia(AML).Due to the rarity of such cases in clinical practice,there have been no relevant case reports so far.CASE SUMMARY A 51-year-old female patient attended the hospital due to throat pain and abnormal blood cells for 4 d.Her diagnosis was acute myelocytic leukemia[M2 type Fms related receptor tyrosine kinase 3,Isocitrate Dehydrogenase 1,Nucleophosmin 1,Neuroblastoma RAS viral oncogene homolog(+)high-risk group].She was treated with"IA"(IDA 10 mg day 1-3 and Ara-C 0.2 g day 1-5)chemotherapy.When her condition improved,the patient was discharged from the hospital,instructed to take medicine as prescribed by the doctor after discharge,and returned to the hospital for further chemotherapy on time.CONCLUSION We report a rare case of first platelet transfusion failure in a patient with AML during induction chemotherapy,which may be related to the production of platelet antibodies induced by antibiotics and excessive tumor load.This also suggests that we should consider the influence of antibiotics when the rare situation of first platelet transfusion failure occurs in patients with AML.When platelet antibodies are produced,immunoglobulins can be used to block antibodies,thereby reducing platelet destruction.For patients with PTR,both immune and non-immune factors need to be considered and combined in clinical practice along with individualized treatment to effectively solve the problem.展开更多
BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for...BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for acute promyelocytic leukemia(APL)combined with PTB is lacking.These patients show an extremely poor prognosis.Therefore,studies should establish efficient treatment options to improve patient survival and prognosis.CASE SUMMARY A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our hospital.Peripheral blood smear revealed 54%blasts.Following bone marrow examinations,variant APL with TNRC18-RARA fusion gene was diagnosed.Chest computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions,partial atelectasis in the lower lobes of both lungs,and the bronchoalveolar lavage fluid gene X-Pert test was positive,indicative of PTB.Carrimycin,ethambutol(EMB),and isoniazid(INH)were administered since he could not receive chemotherapy as the WBC count decreased continuously.After one week of treatment with carrimycin,the patient recovered from fever and received chemotherapy.Chemotherapy was very effective and his white blood cells counts got back to normal.After being given five months with rifampin,EMB and INH and chemotherapy,the patient showed complete remission from pneumonia and APL.CONCLUSION We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy.展开更多
BACKGROUND Rhabdomyosarcoma is a tumor of mesenchymal origin.Secondary leukemia is a complication of previous transformation to other hematologic disorders or is a treatment-related acute myeloid leukemia secondary to...BACKGROUND Rhabdomyosarcoma is a tumor of mesenchymal origin.Secondary leukemia is a complication of previous transformation to other hematologic disorders or is a treatment-related acute myeloid leukemia secondary to cytotoxic chemotherapy or radiation therapy for other malignancies.CASE SUMMARY We present the case of a 36-year-old female patient who was diagnosed with rhabdomyosarcoma and acute myeloid leukemia.Further disease progression was observed after multiline chemotherapy.Eventually,the patient suffered cerebral hemorrhage,which resulted in death.CONCLUSION The incidence of rhabdomyosarcoma in adults is extremely low,and secondary leukemia caused by rhabdomyosarcoma is even rarer.Secondary leukemia has a very poor prognosis and a low overall survival rate.展开更多
Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic r...Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient population.The present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients.Methods:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were evaluated.In addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL.Results:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor growth.Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations.Conclusion:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.展开更多
Acute lymphoblastic leukemia (ALL) is characterized by immature and poorly differentiated B lymphocytes in large numbers in the blood. B cells are distinct from the cell types involved in their development (common lym...Acute lymphoblastic leukemia (ALL) is characterized by immature and poorly differentiated B lymphocytes in large numbers in the blood. B cells are distinct from the cell types involved in their development (common lymphoid progenitor cells, pro-B cells, pre-B cells, and mature cells). The process of B cell maturation depends on precise communication within the cell: signals activate specific genes that are essential for proper development. Errors in this intricate signaling network can lead to issues with B cell function and contribute to disease. B-lineage acute lymphoid leukemias, malignancies of precursor-stage B lymphoid cells inhibit lymphoid differentiation, leading to abnormal cell proliferation and survival. The process of developing leukemia (leukemogenesis) can be triggered by an overproduction of both hematopoietic stem cells (the cells that form all blood cells) and the immature versions of white blood cells called lymphoblasts. Acute lymphoblastic leukemia (ALL) with the presence of the Philadelphia chromosome (ALL Ph) is classified as a high-risk manifestation of the disease, this chromosome is the product of the reciprocal translocation, whose product is a BCR-ABL fusion protein. It is a highly active tyrosine kinase that can transform hematopoietic cells into cytokine-independent. Hyperphosphorylation cascades inhibit the differentiating function of IKZF1 as a tumor suppressor gene which leads to an abnormal proliferation of B cells due to the presence of the Philadelphia chromosome;it inhibits the differentiating process, leukemogenesis involving immature B cells in the bloodstream can result from the uncontrolled growth and division of hematopoietic stem cells and immature lymphoblasts (the precursors to B cells).展开更多
The main goal of this research is to assess the impact of race, age at diagnosis, sex, and phenotype on the incidence and survivability of acute lymphocytic leukemia (ALL) among patients in the United States. By takin...The main goal of this research is to assess the impact of race, age at diagnosis, sex, and phenotype on the incidence and survivability of acute lymphocytic leukemia (ALL) among patients in the United States. By taking these factors into account, the study aims to explore how existing cancer registry data can aid in the early detection and effective treatment of ALL in patients. Our hypothesis was that statistically significant correlations exist between race, age at which patients were diagnosed, sex, and phenotype of the ALL patients, and their rate of incidence and survivability data were evaluated using SEER*Stat statistical software from National Cancer Institute. Analysis of the incidence data revealed that a higher prevalence of ALL was among the Caucasian population. The majority of ALL cases (59%) occurred in patients aged between 0 to 19 years at the time of diagnosis, and 56% of the affected individuals were male. The B-cell phenotype was predominantly associated with ALL cases (73%). When analyzing survivability data, it was observed that the 5-year survival rates slightly exceeded the 10-year survival rates for the respective demographics. Survivability rates of African Americans patients were the lowest compared to Caucasian, Asian, Pacific Islanders, Alaskan Native, Native Americans and others. Survivability rates progressively decreased for older patients. Moreover, this study investigated the typical treatment methods applied to ALL patients, mainly comprising chemotherapy, with occasional supplementation of radiation therapy as required. The study demonstrated the considerable efficacy of chemotherapy in enhancing patients’ chances of survival, while those who remained untreated faced a less favorable prognosis from the disease. Although a significant amount of data and information exists, this study can help doctors in the future by diagnosing patients with certain characteristics. It will further assist the health care professionals in screening potential patients and early detection of cases. This could also save the lives of elderly patients who have a higher mortality rate from this disease.展开更多
Objective:To study the different influence of idarubicin + Arac (IA) therapy and daunorubicin + Arac (DA) therapy on malignant molecule expression of acute myelocytic leukemia. Methods: A total of 56 patients who were...Objective:To study the different influence of idarubicin + Arac (IA) therapy and daunorubicin + Arac (DA) therapy on malignant molecule expression of acute myelocytic leukemia. Methods: A total of 56 patients who were diagnosed with acute myelocytic leukemia in Kashgar Prefecture First People's Hospital between January 2014 and September 2017 were selected as the research subjects and randomly divided into IA group and DA group, and the expression levels of proliferation genes, apoptosis genes and invasion genes in bone marrow tissue were determined after they accepted two courses of different chemotherapy regimens. Results:After two courses of chemotherapy, Daxx, CDX2, MCL1, BCL2, SOX4, S100A6, MMP9, N-cadherin, ICAM-1 and SDF-1 protein expression in bone marrow tissue of IA group were significantly lower than those of DA group whereas SHIP1, Bax and C/EBP protein expression were significantly higher than those of DA group.Conclusion:IA solution for acute myelocytic leukemia can be more effective than DA solution to inhibit the expression of proliferation and invasion genes and increase the expression of apoptosis genes.展开更多
Clinically,arsenic trioxide(ATO)was applied to the treatment of acute promyelocytic leukemia(APL)as a reliable and effective frontline drug.However,the administration regimen of AsⅢwas limited due to its fast clearan...Clinically,arsenic trioxide(ATO)was applied to the treatment of acute promyelocytic leukemia(APL)as a reliable and effective frontline drug.However,the administration regimen of AsⅢwas limited due to its fast clearance,short therapeutic window and toxicity as well.Based on CD71 overexpressed on APL cells,in present study,a transferrin(Tf)-modified liposome(LP)was established firstly to encapsulate AsⅢin arsenic-nickel complex by nickel acetate gradient method.The AsⅢ-loaded liposomes(AsLP)exhibited the feature of acid-sensitive release in vitro.Tf-modified AsLP(Tf-AsLP)were specifically taken up by APL cells and the acidic intracellular environment triggered liposome to release AsⅢwhich stimulated reactive oxygen species level and caspase-3 activity.Tf-AsLP prolonged half-life of AsⅢin blood circulation,lowered systemic toxicity,and promoted apoptosis and induced cell differentiation at lesion site in vivo.Considering that ATO combined with RA is usually applied as the first choice in clinic for APL treatment to improve the therapeutic effect,accordingly,a Tf-modified RA liposome(Tf-RALP)was designed to reduce the severe side effects of free RA and assist Tf-AsLP for better efficacy.As expected,the tumor inhibition rate of Tf-AsLP was improved significantly with the combination of Tf-RALP on subcutaneous tumor model.Furthermore,APL orthotopic NOD/SCID mice model was established by 60CO irradiation and HL-60 cells intravenously injection.The effect of co-administration(Tf-AsLP+Tf-RALP)was also confirmed to conspicuous decrease the number of leukemia cells in the circulatory system and prolong the survival time of APL mice by promoting the APL cells’apoptosis and differentiation in peripheral blood and bone marrow.Collectively,Tf-modified acid-sensitive AsLP could greatly reduce the systemic toxicity of free drug.Moreover,Tf-AsLP combined with Tf-RALP could achieve better efficacy.Thus,transferrinmodified AsⅢliposome would be a novel clinical strategy to improve patient compliance,with promising translation prospects.展开更多
Introduction: Acute Promyelocytic Leukemia (APL) is highly associated with hemostasis alterations. The atypical hemolytic uremic syndrome (aHUS) is a rare type of Thrombotic Microangiopathy (TMA) due to an overactivat...Introduction: Acute Promyelocytic Leukemia (APL) is highly associated with hemostasis alterations. The atypical hemolytic uremic syndrome (aHUS) is a rare type of Thrombotic Microangiopathy (TMA) due to an overactivation of the alternative complement pathway. Case Presentation: A 48-years-old woman was diagnosed with APL and achieved molecular remission after induction therapy. During the second consolidation cycle she presented with TMA. She began treatment with plasma exchange plus corticotherapy but due to aggravation of symptoms Eculizumab was initiated. Thrombotic thrombocytopenic purpura, infections and drug toxicity causes were ruled out. There was no evidence of relapse of the APL. Genetic studies of the hereditary anomalies of the alternative complement pathway were negative and the decision of stopping Eculizumab was made. During maintenance therapy for the APL she presented a severe relapse of the aHUS, requiring dialysis. She re-started treatment with Eculizumab with a progressive hematologic recovery and improvement of renal function. She completed APL treatment without relapse of the leukemia for the moment and continues to be treated with Eculizumab. Conclusion: This is the first published case of coexisting aHUS and APL successfully treated with Eculizumab.展开更多
Objective:To investigate the expression of CXCR, on HL-60 cell line and the proliferation, apoptosis of HL-60 cell line cocultured with bone marrow stromal cells, so as to assess the possibility of 12G5. an anti-CXCR4...Objective:To investigate the expression of CXCR, on HL-60 cell line and the proliferation, apoptosis of HL-60 cell line cocultured with bone marrow stromal cells, so as to assess the possibility of 12G5. an anti-CXCR4 monoclonal antibody, in eradicating the minimal residual disease. Methods:The activity of SDF-1 was inhibited by 10μg/ml 12G5. After treatment with 12G5. the status of adhesion was observed, and the adhesion rates, apoptosis and cell cycles were detected after 24 h of treatment. Cell growth rates were measured by trypan blue exclusion. Cell growth curve was plotted, and the expression of PCNA and apoptosis related protein including PCNA, Bcl-2 and Fas were detected with immunohis-tochemical technique. Results :(1) There was middling degree expression of CXCR4 on HL-60 membrane. From 0 h to 6 h, as the time of 12G5 incubation along, the expression of CXCR4 decreased gradually. (2) After treatment for 24 h, the adhesion rates in the experiment group and the control were (39. 4±7. 9)% and (51. 4±5. 9)%, respectively. (3)After treatment for 24 h, the percentage of HL-60 cells in G0/G1 phase were (55. 21±4. 9)%, and that in S phase and G2/M phase were (30. 40±4. 1)% and (14. 39±5.2)%, respectively, with the corresponding proportions being (44. 67±2. 2) % , (45. 30±3. 7)% . and (10. 03±2. 6)% in the control. (4) The percentage of apoptotic HL-60 cells was (8. 95±1. 7)% in the experiment group, compared to (3. 97±2. 4)% in the control. (5)The survival rates of HL-60 cells decreased markedly at 48 h to 96 h, and the proliferation slowed down at this time duration. (6)The expression of PCNA and Bcl-2 down-regulated significantly, but the Fas protein expression was up-regulated. Conclusion :12G5 could inhibit the capability of adhesion and proliferation of HL-60 cells and it can induce more cells to enter G0/G1 phase and promote apoptosis. It may be helpful by inhibiting the bioactivity of SDF-1 with 12G5 in the therapy of marrow residual disease.展开更多
Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with ...Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.展开更多
BACKGROUND The mixed lineage leukemia(MLL)-eleven-nineteen lysine-rich leukemia(ELL)fusion gene is a rare occurrence among the various MLL fusion genes.We present the first case in which myeloid sarcoma(MS)was the onl...BACKGROUND The mixed lineage leukemia(MLL)-eleven-nineteen lysine-rich leukemia(ELL)fusion gene is a rare occurrence among the various MLL fusion genes.We present the first case in which myeloid sarcoma(MS)was the only manifestation of adult MLL-ELL-positive acute myeloid leukemia(AML).CASE SUMMARY We report a case of a 33-year-old male patient who was admitted in June 2022 with a right occipital area mass measuring approximately 7 cm×8 cm.Blood work was normal.The patient underwent right occipital giant subscalp mass excision and incisional flap grafting.Immunohistochemistry was positive for myeloperoxidase,CD43 and CD45 and negative for CD3,CD20,CD34,and CD56.The bone marrow aspirate showed hypercellularity with 20%myeloblasts.Flow cytometry showed that myeloblasts accounted for 27.21%of the nucleated cells,which expressed CD33,CD38,and CD117.The karyotype was 46,XY,t(11,19)(q23;p13.1),-12,+mar/46,XY.Next-generation sequencing showed a fusion of MLL exon 7 to exon 2 of ELL.A diagnosis of MLL-ELL-positive AML(M2 subtype)with subcutaneous MS was made.CONCLUSION MLL-ELL-positive AML with MS is a rare clinical entity.Additional research is needed to elucidate the molecular mechanisms of the pathogenesis of MS.展开更多
BACKGROUND Mixed-phenotype acute leukemia(MPAL)is characterized by acute undifferentiated leukemia with blasts co-expressing myeloid and lymphoid antigens.However,consensus regarding the ideal management strategy for ...BACKGROUND Mixed-phenotype acute leukemia(MPAL)is characterized by acute undifferentiated leukemia with blasts co-expressing myeloid and lymphoid antigens.However,consensus regarding the ideal management strategy for MPAL is yet to be established,owing to its rarity.CASE SUMMARY A 55-year-old male was diagnosed with T/myeloid MPAL.Vincristine,prednisolone,daunorubicin,and L-asparaginase were administered as induction chemotherapy.Septic shock occurred 10 days after induction,and bone marrow examination following recovery from sepsis revealed refractory disease.Venetoclax and decitabine were administered as chemotherapy-free induction therapy to reduce the infection risk.There were no serious infections,including febrile neutropenia,at the end of the treatment.After receiving two additional cycles of venetoclax/decitabine,the patient underwent haploidentical peripheral blood stem-cell transplantation and achieved complete response(CR)to treatment.CONCLUSION CR was maintained in a patient with MPAL who underwent haploidentical peripheral blood stem-cell transplantation after additional venetoclax/decitabine cycles.展开更多
Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with aberrant T-cell developmental arrest. Individuals with relapsed T-ALL have limited therapeutic alternatives and po...Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with aberrant T-cell developmental arrest. Individuals with relapsed T-ALL have limited therapeutic alternatives and poor prognosis. The mitochondrial function is critical for the T-cell viability. The voltage-dependent anion channel 2 (VDAC2) in the mitochondrial outer membrane, interacts with pro-apoptotic BCL-2 proteins and mediates the apoptosis of several cancer cell lines. Objective: The aim of the current study is to explore the role of VDAC2 in T-ALL cell survival and proliferation. Methods: Publicly available datasets of RNA-seq results were analyzed for expression of VDAC isoforms and T-ALL cell lines were treated with a VDAC2 small molecular inhibitor erastin. A VDAC2 RNA interference (siRNA) was delivered to T-ALL cell lines using a retroviral vector. Functional assays were performed to investigate the VDAC2 siRNA impacts on cell proliferation, apoptosis and survival of T-ALL cells. Results: Our analysis found a high expression of VDAC2 mRNA in various T-ALL cell lines. Public datasets of T-ALL RNA-seq also showed that VDAC2 is highly expressed in T-ALL (116.2 ± 36.7), compared to control groups. Only two T-ALL cell lines showed sensitivity to erastin (20 μM) after 48 hours of incubation, including Jurkat (IC<sub>50</sub> = 3.943 μM) and Molt4 (IC<sub>50</sub> = 3.286 μM), while another two T-ALL cells (CUTLL1 and RPMI 8402) had unstable IC<sub>50</sub>. However, five T-ALL cell lines (LOUCY, CCRF-CEM, P12-ICHI, HPB-ALL, and PEER cells) showed resistance to erastin. On the contrary, all T-ALL cell lines genetically inhibited with VDAC2 siRNA led to more than 80% decrease in VDAC2 mRNA levels, and a Conclusion: VDAC2 is highly expressed in T-ALL cells. The inhibition of VDAC2 significantly decreased cell viability, increased apoptosis, reduced cell proliferation and caused cell cycle sub-G1 arrest of T-ALL cells.展开更多
BACKGROUND Arsenic trioxide(ATO)is recommended for patients who do not achieve molecular remission or who have molecular or morphologic relapse.However,there are no guidelines for adjusting ATO dosage in patients with...BACKGROUND Arsenic trioxide(ATO)is recommended for patients who do not achieve molecular remission or who have molecular or morphologic relapse.However,there are no guidelines for adjusting ATO dosage in patients with severe renal failure or on dialysis.Herein,we report the successful treatment of relapsed acute promyelocytic leukemia(APL)in a patient on hemodialysis with ATO single agent and review the cases in literature.CASE SUMMARY A 46-year-old woman who has been on hemodialysis to chronic glomerulonephritis for 15 years visited our hospital for pancytopenia.She had been seen for pancytopenia 3 years ago and had been diagnosed with APL.She also received chemotherapy for APL but unfortunately was lost to follow-up after her second consolidation chemotherapy.She was noted to have pancytopenia by her nephrologist during hemodialysis 1 mo ago.Bone marrow biopsy and reverse transcriptase-polymerase chain reaction(RT-PCR)tests revealed a diagnosis of relapsed APL.Treatment for relapsed APL with ATO single agent was started and she achieved molecular remission after administering 24 doses of ATO.Thus far,four consolidation therapies have been performed with the ATO single agent,and,to date,the molecular remission has been maintained as negative promyelocytic leukemia/retinoic acid receptor-αfusion gene as confirmed by RTPCR testing for two years.CONCLUSION This is a rare case of relapsed APL successfully treated with the single agent ATO in a patient on hemodialysis.展开更多
BACKGROUND Chromosome i(17)(q10)abnormality is mainly associated with chronic myeloid leukemia(CML),myelodysplastic syndrome/myeloproliferative tumors(MDS/MPD),and acute myeloid leukemia(AML).The role of i(17)(q10)in ...BACKGROUND Chromosome i(17)(q10)abnormality is mainly associated with chronic myeloid leukemia(CML),myelodysplastic syndrome/myeloproliferative tumors(MDS/MPD),and acute myeloid leukemia(AML).The role of i(17)(q10)in AML is still unknown,the differences between AML and acute promyelocytic leukemia(APL)-like AML with i(17)(q10)need more research.This study aimed to investigate the clinical characteristics and laboratory evidence of 2 AML cases with i(17)(q10),similar to APL phenotype.CASE SUMMARY Both pediatric patients were males;case 1 had newly diagnosed AML,and case 2 showed relapsed tumor after 1 year of drug withdrawal.Bone marrow cell morphology,chromosome karyotype analysis,Fully-instrumented submersible housing test,immunological assays,molecular biological methods,and blood tumor panoramic gene test were performed.All-trans retinoic acid(ATRA)combined with arsenic acid(As2O3)were used in the first course of treatment.Bone marrow was dominated by abnormal promyelocytic granulocytes.Karyotype test revealed i(17)(q10)isochromosome.Immunological phenotype mainly included positive expressions of CD9,CD13,CD33,and CD38.Case 1 suffered intracranial hemorrhage after re-chemotherapy and died on D162.For case 2,on D145 and D265,bone marrow promyelocytic granulocytes accounted for 2%.Flow cytometric residual lesion detection showed no abnormal immunophenotype cells.The copy number of WT1 gene in two cases were 1087 and 1010,respectively,and the expression rates were 55.29% and 59.5%,respectively.CONCLUSION ATRA,As2O3,and chemotherapy may be ineffective in treating APL-like AML with i(17)(q10)but without t(15;17)and PML-RARA fusion gene.展开更多
BACKGROUND Therapy-related acute promyelocytic leukemia(t-APL)is a rare complication observed in solitary bone plasmacytoma(SBP),and SBP after radiotherapy evolving to APL harboring the FMS-like tyrosine kinase 3-inte...BACKGROUND Therapy-related acute promyelocytic leukemia(t-APL)is a rare complication observed in solitary bone plasmacytoma(SBP),and SBP after radiotherapy evolving to APL harboring the FMS-like tyrosine kinase 3-internal tandem duplication(FLT3-ITD)mutation has never been reported.Here,we present the first case reported until now.CASE SUMMARY We describe a 64-year-old woman who presented with lumbar pain and was initially diagnosed with SBP.However,after one year of radiotherapy treatment,this patient experienced a long-standing bone-marrow-suppressive period and finally developed APL harboring the FLT3-ITD mutation,as confirmed by analyses of clinical features,bone marrow morphology,flow cytometry,cytogenetic examination,and molecular biology.On admission,the patient had disseminated intravascular coagulation and intracranial hemorrhage,and the peripheral blood and bone marrow smear displayed abundant abnormal promyelocytes.Unfortunately,she died when the definite diagnosis was made.CONCLUSION The patient with t-APL harboring FLT3-ITD mutation evolving from SBP after radiotherapy had not been reported and had poor clinical outcomes.FLT3-ITD mutation in t-APL may be a potential pathogenesis of leukemogenesis.We should consider the potential risk of secondary neoplasms in SBP patients after radiotherapy.展开更多
Therapy-related acute myeloid leukemia(t-AML) refers to a heterogeneous group of myeloid neoplasms that develop in patients following extensive exposure to either cytotoxic agents or radiation.The development of t-AML...Therapy-related acute myeloid leukemia(t-AML) refers to a heterogeneous group of myeloid neoplasms that develop in patients following extensive exposure to either cytotoxic agents or radiation.The development of t-AML has been reported following treatment of cancers ranging from hematological malignancies to solid tumors; however, to our knowledge, t-AML has never been reported following treatment of gastric cancer.In this study, we report the development of t-acute promyelocytic leukemia in a cT 4N1M0 gastric cancer patient after an approximate 44 mo latency period following treatment with 4 cycles of oxaliplatin(OXP)(85 mg/m2 on day 1) plus capecitabine(1250 mg/m2 orally twice daily on days 1-14) in combination with recombinant human granulocyte-colony stimulating factor treatment.Karyotype analysis of the patient revealed 46,XY,t(15;17)(q22;q21)[15]/46,idem,-9,+add(9)(p22)[2]/46,XY[3], which, according to previous studies, includes some "favorable" genetic abnormalities.The patient was then treated with all-trans retinoic acid(ATRA, 25 mg/m2/d) plus arsenic trioxide(ATO, 10 mg/d) and attained complete remission.Our case illuminated the role of certain cytotoxic agents in the induction of t-AML following gastric cancer treatment.We recommend instituting a mandatory additional evaluation for patients undergoing these therapies in the future.展开更多
BACKGROUND Direct infiltration of the pancreas by acute myeloid leukemia(AML)with acute pancreatitis(AP)as an initial symptom is extremely rare.Only once in the literature,the leukemia cells in AML have been implicate...BACKGROUND Direct infiltration of the pancreas by acute myeloid leukemia(AML)with acute pancreatitis(AP)as an initial symptom is extremely rare.Only once in the literature,the leukemia cells in AML have been implicated as the cause of AP.Pancreatitis caused by a rare predisposing factor is often misdiagnosed as idiopathic pancreatitis or pancreatitis of other common causes.Severe AP(SAP)progresses rapidly with a high fatality rate.Therefore,it is important to identify the predisposing factors in the early stage of SAP,evaluate the condition,determine prognosis,formulate treatment plans,and prevent a recurrence.Here,we describe a case of SAP due to AML.CASE SUMMARY A 61-year-old man presented to the hospital with fever and persistent abdominal pain.Blood analysis presented significantly elevated serum amylase and severe thrombocytopenia.Computed tomography examination of the abdomen revealed peripancreatic inflammatory effusion.The patient had no common etiologies and risk factors for AP,but the concurrent severe thrombocytopenia could not be explained by pancreatitis.Finally,the bone marrow aspirate and biopsy inspection revealed the underlying reason for pancreatitis,AML(M2 type based on the French-American-British classifications system).CONCLUSION Direct infiltration of the pancrease by acute leukemia,particularly AML cells,is an infrequent cause of AP.Therefore,although AP is a rare extramedullary infilt-ration characteristic for AML patients,it should be considered when determining the etiology of AP.展开更多
基金Supported by Innovation Platform and Talent Program of Hunan Province,No.2021SK4050.
文摘BACKGROUND Platelet transfusion is of great significance in the treatment of thrombocytopenia caused by myelosuppression during intensive chemotherapy in patients with acute leukemia.In recent years,with platelet transfusion increasing,ineffective platelet transfusion has become increasingly prominent.Generally speaking,platelet antibodies can be produced after repeated transfusion,thus rendering subsequent platelet transfusion ineffective.We report a case of first platelet transfusion refractoriness(PTR)in a patient with acute myelocytic leukemia(AML).Due to the rarity of such cases in clinical practice,there have been no relevant case reports so far.CASE SUMMARY A 51-year-old female patient attended the hospital due to throat pain and abnormal blood cells for 4 d.Her diagnosis was acute myelocytic leukemia[M2 type Fms related receptor tyrosine kinase 3,Isocitrate Dehydrogenase 1,Nucleophosmin 1,Neuroblastoma RAS viral oncogene homolog(+)high-risk group].She was treated with"IA"(IDA 10 mg day 1-3 and Ara-C 0.2 g day 1-5)chemotherapy.When her condition improved,the patient was discharged from the hospital,instructed to take medicine as prescribed by the doctor after discharge,and returned to the hospital for further chemotherapy on time.CONCLUSION We report a rare case of first platelet transfusion failure in a patient with AML during induction chemotherapy,which may be related to the production of platelet antibodies induced by antibiotics and excessive tumor load.This also suggests that we should consider the influence of antibiotics when the rare situation of first platelet transfusion failure occurs in patients with AML.When platelet antibodies are produced,immunoglobulins can be used to block antibodies,thereby reducing platelet destruction.For patients with PTR,both immune and non-immune factors need to be considered and combined in clinical practice along with individualized treatment to effectively solve the problem.
文摘BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for acute promyelocytic leukemia(APL)combined with PTB is lacking.These patients show an extremely poor prognosis.Therefore,studies should establish efficient treatment options to improve patient survival and prognosis.CASE SUMMARY A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our hospital.Peripheral blood smear revealed 54%blasts.Following bone marrow examinations,variant APL with TNRC18-RARA fusion gene was diagnosed.Chest computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions,partial atelectasis in the lower lobes of both lungs,and the bronchoalveolar lavage fluid gene X-Pert test was positive,indicative of PTB.Carrimycin,ethambutol(EMB),and isoniazid(INH)were administered since he could not receive chemotherapy as the WBC count decreased continuously.After one week of treatment with carrimycin,the patient recovered from fever and received chemotherapy.Chemotherapy was very effective and his white blood cells counts got back to normal.After being given five months with rifampin,EMB and INH and chemotherapy,the patient showed complete remission from pneumonia and APL.CONCLUSION We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy.
文摘BACKGROUND Rhabdomyosarcoma is a tumor of mesenchymal origin.Secondary leukemia is a complication of previous transformation to other hematologic disorders or is a treatment-related acute myeloid leukemia secondary to cytotoxic chemotherapy or radiation therapy for other malignancies.CASE SUMMARY We present the case of a 36-year-old female patient who was diagnosed with rhabdomyosarcoma and acute myeloid leukemia.Further disease progression was observed after multiline chemotherapy.Eventually,the patient suffered cerebral hemorrhage,which resulted in death.CONCLUSION The incidence of rhabdomyosarcoma in adults is extremely low,and secondary leukemia caused by rhabdomyosarcoma is even rarer.Secondary leukemia has a very poor prognosis and a low overall survival rate.
基金funded by the National Natural Science Foundation of China(No.81770126,No.81900160,No.81800163,No.22025702,and No.91853203)the Fujian Natural Science Foundation of China(No.2020J011246 and No.2021J011359)+2 种基金the Foundation of Health and Family Planning Commission of Fujian Province of China(No.2020GGB054)the Xiamen Municipal Bureau of Science and Technology(No.3502Z20209003)the Fundamental Research Funds for the Central Universities of China(No.20720190101).
文摘Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient population.The present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients.Methods:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were evaluated.In addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL.Results:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor growth.Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations.Conclusion:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.
文摘Acute lymphoblastic leukemia (ALL) is characterized by immature and poorly differentiated B lymphocytes in large numbers in the blood. B cells are distinct from the cell types involved in their development (common lymphoid progenitor cells, pro-B cells, pre-B cells, and mature cells). The process of B cell maturation depends on precise communication within the cell: signals activate specific genes that are essential for proper development. Errors in this intricate signaling network can lead to issues with B cell function and contribute to disease. B-lineage acute lymphoid leukemias, malignancies of precursor-stage B lymphoid cells inhibit lymphoid differentiation, leading to abnormal cell proliferation and survival. The process of developing leukemia (leukemogenesis) can be triggered by an overproduction of both hematopoietic stem cells (the cells that form all blood cells) and the immature versions of white blood cells called lymphoblasts. Acute lymphoblastic leukemia (ALL) with the presence of the Philadelphia chromosome (ALL Ph) is classified as a high-risk manifestation of the disease, this chromosome is the product of the reciprocal translocation, whose product is a BCR-ABL fusion protein. It is a highly active tyrosine kinase that can transform hematopoietic cells into cytokine-independent. Hyperphosphorylation cascades inhibit the differentiating function of IKZF1 as a tumor suppressor gene which leads to an abnormal proliferation of B cells due to the presence of the Philadelphia chromosome;it inhibits the differentiating process, leukemogenesis involving immature B cells in the bloodstream can result from the uncontrolled growth and division of hematopoietic stem cells and immature lymphoblasts (the precursors to B cells).
文摘The main goal of this research is to assess the impact of race, age at diagnosis, sex, and phenotype on the incidence and survivability of acute lymphocytic leukemia (ALL) among patients in the United States. By taking these factors into account, the study aims to explore how existing cancer registry data can aid in the early detection and effective treatment of ALL in patients. Our hypothesis was that statistically significant correlations exist between race, age at which patients were diagnosed, sex, and phenotype of the ALL patients, and their rate of incidence and survivability data were evaluated using SEER*Stat statistical software from National Cancer Institute. Analysis of the incidence data revealed that a higher prevalence of ALL was among the Caucasian population. The majority of ALL cases (59%) occurred in patients aged between 0 to 19 years at the time of diagnosis, and 56% of the affected individuals were male. The B-cell phenotype was predominantly associated with ALL cases (73%). When analyzing survivability data, it was observed that the 5-year survival rates slightly exceeded the 10-year survival rates for the respective demographics. Survivability rates of African Americans patients were the lowest compared to Caucasian, Asian, Pacific Islanders, Alaskan Native, Native Americans and others. Survivability rates progressively decreased for older patients. Moreover, this study investigated the typical treatment methods applied to ALL patients, mainly comprising chemotherapy, with occasional supplementation of radiation therapy as required. The study demonstrated the considerable efficacy of chemotherapy in enhancing patients’ chances of survival, while those who remained untreated faced a less favorable prognosis from the disease. Although a significant amount of data and information exists, this study can help doctors in the future by diagnosing patients with certain characteristics. It will further assist the health care professionals in screening potential patients and early detection of cases. This could also save the lives of elderly patients who have a higher mortality rate from this disease.
文摘Objective:To study the different influence of idarubicin + Arac (IA) therapy and daunorubicin + Arac (DA) therapy on malignant molecule expression of acute myelocytic leukemia. Methods: A total of 56 patients who were diagnosed with acute myelocytic leukemia in Kashgar Prefecture First People's Hospital between January 2014 and September 2017 were selected as the research subjects and randomly divided into IA group and DA group, and the expression levels of proliferation genes, apoptosis genes and invasion genes in bone marrow tissue were determined after they accepted two courses of different chemotherapy regimens. Results:After two courses of chemotherapy, Daxx, CDX2, MCL1, BCL2, SOX4, S100A6, MMP9, N-cadherin, ICAM-1 and SDF-1 protein expression in bone marrow tissue of IA group were significantly lower than those of DA group whereas SHIP1, Bax and C/EBP protein expression were significantly higher than those of DA group.Conclusion:IA solution for acute myelocytic leukemia can be more effective than DA solution to inhibit the expression of proliferation and invasion genes and increase the expression of apoptosis genes.
基金supported by the Science and Technology Commission of Shanghai Municipality (20S11902600)the National Natural Science Foundation of China (82172615)the PDH-SPFDU Joint Research Fund (RHJJ2018-05)
文摘Clinically,arsenic trioxide(ATO)was applied to the treatment of acute promyelocytic leukemia(APL)as a reliable and effective frontline drug.However,the administration regimen of AsⅢwas limited due to its fast clearance,short therapeutic window and toxicity as well.Based on CD71 overexpressed on APL cells,in present study,a transferrin(Tf)-modified liposome(LP)was established firstly to encapsulate AsⅢin arsenic-nickel complex by nickel acetate gradient method.The AsⅢ-loaded liposomes(AsLP)exhibited the feature of acid-sensitive release in vitro.Tf-modified AsLP(Tf-AsLP)were specifically taken up by APL cells and the acidic intracellular environment triggered liposome to release AsⅢwhich stimulated reactive oxygen species level and caspase-3 activity.Tf-AsLP prolonged half-life of AsⅢin blood circulation,lowered systemic toxicity,and promoted apoptosis and induced cell differentiation at lesion site in vivo.Considering that ATO combined with RA is usually applied as the first choice in clinic for APL treatment to improve the therapeutic effect,accordingly,a Tf-modified RA liposome(Tf-RALP)was designed to reduce the severe side effects of free RA and assist Tf-AsLP for better efficacy.As expected,the tumor inhibition rate of Tf-AsLP was improved significantly with the combination of Tf-RALP on subcutaneous tumor model.Furthermore,APL orthotopic NOD/SCID mice model was established by 60CO irradiation and HL-60 cells intravenously injection.The effect of co-administration(Tf-AsLP+Tf-RALP)was also confirmed to conspicuous decrease the number of leukemia cells in the circulatory system and prolong the survival time of APL mice by promoting the APL cells’apoptosis and differentiation in peripheral blood and bone marrow.Collectively,Tf-modified acid-sensitive AsLP could greatly reduce the systemic toxicity of free drug.Moreover,Tf-AsLP combined with Tf-RALP could achieve better efficacy.Thus,transferrinmodified AsⅢliposome would be a novel clinical strategy to improve patient compliance,with promising translation prospects.
文摘Introduction: Acute Promyelocytic Leukemia (APL) is highly associated with hemostasis alterations. The atypical hemolytic uremic syndrome (aHUS) is a rare type of Thrombotic Microangiopathy (TMA) due to an overactivation of the alternative complement pathway. Case Presentation: A 48-years-old woman was diagnosed with APL and achieved molecular remission after induction therapy. During the second consolidation cycle she presented with TMA. She began treatment with plasma exchange plus corticotherapy but due to aggravation of symptoms Eculizumab was initiated. Thrombotic thrombocytopenic purpura, infections and drug toxicity causes were ruled out. There was no evidence of relapse of the APL. Genetic studies of the hereditary anomalies of the alternative complement pathway were negative and the decision of stopping Eculizumab was made. During maintenance therapy for the APL she presented a severe relapse of the aHUS, requiring dialysis. She re-started treatment with Eculizumab with a progressive hematologic recovery and improvement of renal function. She completed APL treatment without relapse of the leukemia for the moment and continues to be treated with Eculizumab. Conclusion: This is the first published case of coexisting aHUS and APL successfully treated with Eculizumab.
基金Supported by the National Natural Scientific Foundation of China (No. 30170396)
文摘Objective:To investigate the expression of CXCR, on HL-60 cell line and the proliferation, apoptosis of HL-60 cell line cocultured with bone marrow stromal cells, so as to assess the possibility of 12G5. an anti-CXCR4 monoclonal antibody, in eradicating the minimal residual disease. Methods:The activity of SDF-1 was inhibited by 10μg/ml 12G5. After treatment with 12G5. the status of adhesion was observed, and the adhesion rates, apoptosis and cell cycles were detected after 24 h of treatment. Cell growth rates were measured by trypan blue exclusion. Cell growth curve was plotted, and the expression of PCNA and apoptosis related protein including PCNA, Bcl-2 and Fas were detected with immunohis-tochemical technique. Results :(1) There was middling degree expression of CXCR4 on HL-60 membrane. From 0 h to 6 h, as the time of 12G5 incubation along, the expression of CXCR4 decreased gradually. (2) After treatment for 24 h, the adhesion rates in the experiment group and the control were (39. 4±7. 9)% and (51. 4±5. 9)%, respectively. (3)After treatment for 24 h, the percentage of HL-60 cells in G0/G1 phase were (55. 21±4. 9)%, and that in S phase and G2/M phase were (30. 40±4. 1)% and (14. 39±5.2)%, respectively, with the corresponding proportions being (44. 67±2. 2) % , (45. 30±3. 7)% . and (10. 03±2. 6)% in the control. (4) The percentage of apoptotic HL-60 cells was (8. 95±1. 7)% in the experiment group, compared to (3. 97±2. 4)% in the control. (5)The survival rates of HL-60 cells decreased markedly at 48 h to 96 h, and the proliferation slowed down at this time duration. (6)The expression of PCNA and Bcl-2 down-regulated significantly, but the Fas protein expression was up-regulated. Conclusion :12G5 could inhibit the capability of adhesion and proliferation of HL-60 cells and it can induce more cells to enter G0/G1 phase and promote apoptosis. It may be helpful by inhibiting the bioactivity of SDF-1 with 12G5 in the therapy of marrow residual disease.
基金the National Natural Science Foundation of China(No.81960043 and No.81600180)Natural Science Foundation of Jiangxi Province(No.20192ACB20030 and No.20203BBGL73197)Science and Technology Innovation Base Construction Project of Jiangxi Province(No.20212BCG74001 and No.20211ZDG02006).
文摘Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.
基金Supported by Scientific Research Project of Anhui Provincial Health Commission,No.AHWJ2021b005.
文摘BACKGROUND The mixed lineage leukemia(MLL)-eleven-nineteen lysine-rich leukemia(ELL)fusion gene is a rare occurrence among the various MLL fusion genes.We present the first case in which myeloid sarcoma(MS)was the only manifestation of adult MLL-ELL-positive acute myeloid leukemia(AML).CASE SUMMARY We report a case of a 33-year-old male patient who was admitted in June 2022 with a right occipital area mass measuring approximately 7 cm×8 cm.Blood work was normal.The patient underwent right occipital giant subscalp mass excision and incisional flap grafting.Immunohistochemistry was positive for myeloperoxidase,CD43 and CD45 and negative for CD3,CD20,CD34,and CD56.The bone marrow aspirate showed hypercellularity with 20%myeloblasts.Flow cytometry showed that myeloblasts accounted for 27.21%of the nucleated cells,which expressed CD33,CD38,and CD117.The karyotype was 46,XY,t(11,19)(q23;p13.1),-12,+mar/46,XY.Next-generation sequencing showed a fusion of MLL exon 7 to exon 2 of ELL.A diagnosis of MLL-ELL-positive AML(M2 subtype)with subcutaneous MS was made.CONCLUSION MLL-ELL-positive AML with MS is a rare clinical entity.Additional research is needed to elucidate the molecular mechanisms of the pathogenesis of MS.
文摘BACKGROUND Mixed-phenotype acute leukemia(MPAL)is characterized by acute undifferentiated leukemia with blasts co-expressing myeloid and lymphoid antigens.However,consensus regarding the ideal management strategy for MPAL is yet to be established,owing to its rarity.CASE SUMMARY A 55-year-old male was diagnosed with T/myeloid MPAL.Vincristine,prednisolone,daunorubicin,and L-asparaginase were administered as induction chemotherapy.Septic shock occurred 10 days after induction,and bone marrow examination following recovery from sepsis revealed refractory disease.Venetoclax and decitabine were administered as chemotherapy-free induction therapy to reduce the infection risk.There were no serious infections,including febrile neutropenia,at the end of the treatment.After receiving two additional cycles of venetoclax/decitabine,the patient underwent haploidentical peripheral blood stem-cell transplantation and achieved complete response(CR)to treatment.CONCLUSION CR was maintained in a patient with MPAL who underwent haploidentical peripheral blood stem-cell transplantation after additional venetoclax/decitabine cycles.
文摘Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with aberrant T-cell developmental arrest. Individuals with relapsed T-ALL have limited therapeutic alternatives and poor prognosis. The mitochondrial function is critical for the T-cell viability. The voltage-dependent anion channel 2 (VDAC2) in the mitochondrial outer membrane, interacts with pro-apoptotic BCL-2 proteins and mediates the apoptosis of several cancer cell lines. Objective: The aim of the current study is to explore the role of VDAC2 in T-ALL cell survival and proliferation. Methods: Publicly available datasets of RNA-seq results were analyzed for expression of VDAC isoforms and T-ALL cell lines were treated with a VDAC2 small molecular inhibitor erastin. A VDAC2 RNA interference (siRNA) was delivered to T-ALL cell lines using a retroviral vector. Functional assays were performed to investigate the VDAC2 siRNA impacts on cell proliferation, apoptosis and survival of T-ALL cells. Results: Our analysis found a high expression of VDAC2 mRNA in various T-ALL cell lines. Public datasets of T-ALL RNA-seq also showed that VDAC2 is highly expressed in T-ALL (116.2 ± 36.7), compared to control groups. Only two T-ALL cell lines showed sensitivity to erastin (20 μM) after 48 hours of incubation, including Jurkat (IC<sub>50</sub> = 3.943 μM) and Molt4 (IC<sub>50</sub> = 3.286 μM), while another two T-ALL cells (CUTLL1 and RPMI 8402) had unstable IC<sub>50</sub>. However, five T-ALL cell lines (LOUCY, CCRF-CEM, P12-ICHI, HPB-ALL, and PEER cells) showed resistance to erastin. On the contrary, all T-ALL cell lines genetically inhibited with VDAC2 siRNA led to more than 80% decrease in VDAC2 mRNA levels, and a Conclusion: VDAC2 is highly expressed in T-ALL cells. The inhibition of VDAC2 significantly decreased cell viability, increased apoptosis, reduced cell proliferation and caused cell cycle sub-G1 arrest of T-ALL cells.
基金Supported by Research fund from Chosun University,2020.
文摘BACKGROUND Arsenic trioxide(ATO)is recommended for patients who do not achieve molecular remission or who have molecular or morphologic relapse.However,there are no guidelines for adjusting ATO dosage in patients with severe renal failure or on dialysis.Herein,we report the successful treatment of relapsed acute promyelocytic leukemia(APL)in a patient on hemodialysis with ATO single agent and review the cases in literature.CASE SUMMARY A 46-year-old woman who has been on hemodialysis to chronic glomerulonephritis for 15 years visited our hospital for pancytopenia.She had been seen for pancytopenia 3 years ago and had been diagnosed with APL.She also received chemotherapy for APL but unfortunately was lost to follow-up after her second consolidation chemotherapy.She was noted to have pancytopenia by her nephrologist during hemodialysis 1 mo ago.Bone marrow biopsy and reverse transcriptase-polymerase chain reaction(RT-PCR)tests revealed a diagnosis of relapsed APL.Treatment for relapsed APL with ATO single agent was started and she achieved molecular remission after administering 24 doses of ATO.Thus far,four consolidation therapies have been performed with the ATO single agent,and,to date,the molecular remission has been maintained as negative promyelocytic leukemia/retinoic acid receptor-αfusion gene as confirmed by RTPCR testing for two years.CONCLUSION This is a rare case of relapsed APL successfully treated with the single agent ATO in a patient on hemodialysis.
基金Supported by Shaanxi Natural Science Foundation,No.2020SF-004.
文摘BACKGROUND Chromosome i(17)(q10)abnormality is mainly associated with chronic myeloid leukemia(CML),myelodysplastic syndrome/myeloproliferative tumors(MDS/MPD),and acute myeloid leukemia(AML).The role of i(17)(q10)in AML is still unknown,the differences between AML and acute promyelocytic leukemia(APL)-like AML with i(17)(q10)need more research.This study aimed to investigate the clinical characteristics and laboratory evidence of 2 AML cases with i(17)(q10),similar to APL phenotype.CASE SUMMARY Both pediatric patients were males;case 1 had newly diagnosed AML,and case 2 showed relapsed tumor after 1 year of drug withdrawal.Bone marrow cell morphology,chromosome karyotype analysis,Fully-instrumented submersible housing test,immunological assays,molecular biological methods,and blood tumor panoramic gene test were performed.All-trans retinoic acid(ATRA)combined with arsenic acid(As2O3)were used in the first course of treatment.Bone marrow was dominated by abnormal promyelocytic granulocytes.Karyotype test revealed i(17)(q10)isochromosome.Immunological phenotype mainly included positive expressions of CD9,CD13,CD33,and CD38.Case 1 suffered intracranial hemorrhage after re-chemotherapy and died on D162.For case 2,on D145 and D265,bone marrow promyelocytic granulocytes accounted for 2%.Flow cytometric residual lesion detection showed no abnormal immunophenotype cells.The copy number of WT1 gene in two cases were 1087 and 1010,respectively,and the expression rates were 55.29% and 59.5%,respectively.CONCLUSION ATRA,As2O3,and chemotherapy may be ineffective in treating APL-like AML with i(17)(q10)but without t(15;17)and PML-RARA fusion gene.
基金Natural Science Foundation of Zhejiang Province,No.LY19H290003Zhejiang Provincial Medical and Health Science and Technology Project,No.2020KY196and Foundation of Zhejiang Province Chinese Medicine Science and Technology Planes,No.2017ZB030.
文摘BACKGROUND Therapy-related acute promyelocytic leukemia(t-APL)is a rare complication observed in solitary bone plasmacytoma(SBP),and SBP after radiotherapy evolving to APL harboring the FMS-like tyrosine kinase 3-internal tandem duplication(FLT3-ITD)mutation has never been reported.Here,we present the first case reported until now.CASE SUMMARY We describe a 64-year-old woman who presented with lumbar pain and was initially diagnosed with SBP.However,after one year of radiotherapy treatment,this patient experienced a long-standing bone-marrow-suppressive period and finally developed APL harboring the FLT3-ITD mutation,as confirmed by analyses of clinical features,bone marrow morphology,flow cytometry,cytogenetic examination,and molecular biology.On admission,the patient had disseminated intravascular coagulation and intracranial hemorrhage,and the peripheral blood and bone marrow smear displayed abundant abnormal promyelocytes.Unfortunately,she died when the definite diagnosis was made.CONCLUSION The patient with t-APL harboring FLT3-ITD mutation evolving from SBP after radiotherapy had not been reported and had poor clinical outcomes.FLT3-ITD mutation in t-APL may be a potential pathogenesis of leukemogenesis.We should consider the potential risk of secondary neoplasms in SBP patients after radiotherapy.
基金Supported by National Natural Science Foundation of China,No.81173403
文摘Therapy-related acute myeloid leukemia(t-AML) refers to a heterogeneous group of myeloid neoplasms that develop in patients following extensive exposure to either cytotoxic agents or radiation.The development of t-AML has been reported following treatment of cancers ranging from hematological malignancies to solid tumors; however, to our knowledge, t-AML has never been reported following treatment of gastric cancer.In this study, we report the development of t-acute promyelocytic leukemia in a cT 4N1M0 gastric cancer patient after an approximate 44 mo latency period following treatment with 4 cycles of oxaliplatin(OXP)(85 mg/m2 on day 1) plus capecitabine(1250 mg/m2 orally twice daily on days 1-14) in combination with recombinant human granulocyte-colony stimulating factor treatment.Karyotype analysis of the patient revealed 46,XY,t(15;17)(q22;q21)[15]/46,idem,-9,+add(9)(p22)[2]/46,XY[3], which, according to previous studies, includes some "favorable" genetic abnormalities.The patient was then treated with all-trans retinoic acid(ATRA, 25 mg/m2/d) plus arsenic trioxide(ATO, 10 mg/d) and attained complete remission.Our case illuminated the role of certain cytotoxic agents in the induction of t-AML following gastric cancer treatment.We recommend instituting a mandatory additional evaluation for patients undergoing these therapies in the future.
文摘BACKGROUND Direct infiltration of the pancreas by acute myeloid leukemia(AML)with acute pancreatitis(AP)as an initial symptom is extremely rare.Only once in the literature,the leukemia cells in AML have been implicated as the cause of AP.Pancreatitis caused by a rare predisposing factor is often misdiagnosed as idiopathic pancreatitis or pancreatitis of other common causes.Severe AP(SAP)progresses rapidly with a high fatality rate.Therefore,it is important to identify the predisposing factors in the early stage of SAP,evaluate the condition,determine prognosis,formulate treatment plans,and prevent a recurrence.Here,we describe a case of SAP due to AML.CASE SUMMARY A 61-year-old man presented to the hospital with fever and persistent abdominal pain.Blood analysis presented significantly elevated serum amylase and severe thrombocytopenia.Computed tomography examination of the abdomen revealed peripancreatic inflammatory effusion.The patient had no common etiologies and risk factors for AP,but the concurrent severe thrombocytopenia could not be explained by pancreatitis.Finally,the bone marrow aspirate and biopsy inspection revealed the underlying reason for pancreatitis,AML(M2 type based on the French-American-British classifications system).CONCLUSION Direct infiltration of the pancrease by acute leukemia,particularly AML cells,is an infrequent cause of AP.Therefore,although AP is a rare extramedullary infilt-ration characteristic for AML patients,it should be considered when determining the etiology of AP.