Multiple lymphomatous polyposis (MLP) is an unusual form of non-Hodgkin's lymphoma characterized by polyps throughout the gastrointestinal tract. It has been reported that most MLP are observed in cases with mantl...Multiple lymphomatous polyposis (MLP) is an unusual form of non-Hodgkin's lymphoma characterized by polyps throughout the gastrointestinal tract. It has been reported that most MLP are observed in cases with mantle cell lymphoma of B-cell type. We herein present a case of a 66-year-old man with adult T-cell leukemia/lymphoma (ATLL). Colonoscopy revealed MLP throughout the colon and histopathological findings of ATLL cell infiltration. The patient died despite combination of chemotherapy. The literature of manifestations of colonic involvement of ATLL isreviewed and the importance of endoscopic evaluation to differentiate ATLL intestinal lesions from opportunistic infectious enterocolitis is discussed.展开更多
Tuberculosis (TB) is a major public health problem worldwide and a large number of fatal cases are still reported. Immunocompetent individuals are naturally susceptible to TB, and immunocompromised patients have a gre...Tuberculosis (TB) is a major public health problem worldwide and a large number of fatal cases are still reported. Immunocompetent individuals are naturally susceptible to TB, and immunocompromised patients have a greater risk of infection. Although patients with adult T-cell leukemia/lymphoma (ATL) are in an immunosuppressed condition, there is only one reported case of TB accompanied with ATL in the English- language literature in the field of dermatology. Here, we report two patients with chronic-type ATL infected with TB manifesting as cutaneous solitary masses. Case 1 was a 58-year-old woman diagnosed with lumbar abscess with pulmonary TB. Case 2 was an 84-year-old woman diagnosed with tuberculous lymphadenitis in the left cervical region. It is important to raise the differential diagnosis of TB and perform tissue culture for acid-fast bacilli as well as Interferon-Gamma release assay test when dermatologists encounter mass lesions in patients with ATL.展开更多
Adult T-cell leukemia( ATL) is a mature T-cell malignancy caused by human T-cell leukemia virus type I infection, and 10%-25% of patients show central nervous system( CNS) involvement. CNS involvement significantly re...Adult T-cell leukemia( ATL) is a mature T-cell malignancy caused by human T-cell leukemia virus type I infection, and 10%-25% of patients show central nervous system( CNS) involvement. CNS involvement significantly reduces survival and there are no effective treatments for CNS involvement. Therefore, an appropriate animal model is required to evaluate the inhibitory effects of novel drugs on the progression of ATL with CNS involvement. Here, we established a mouse model of ATL with CNS involvement using NOD.Cg-Prkdc~ (scid) Il2 rg ^(tm1Wjl)/SzJ mice inoculated with ATL cells intramuscularly in the postauricular region, and these mice showed paraparesis. Of the 10 mice inoculated with ATL cells intramuscularly(I.M.) at 5 weeks of age, 8(80%) showed paraparesis, whereas none of the 10 mice inoculated with ATL cells subcutaneously(S.C.) showed paraparesis. In the I.M. group, PCR detected HTLV-1-specific genes in the thoracic and lumbar vertebrae; however, in the S.C. group, the vertebrae were negative for HTLV-1 genes. Histological analysis revealed a particularly high incidence of tumors, characterized by accumulation of the injected cells, in the thoracic vertebrae of mice in the I.M. group. Tumor cell infiltration was relatively high in the bone marrow. Spinal cord compression caused by invasion of the tumor mass outside the pia mater was observed in the thoracic vertebrae of the spinal cord. In conclusion, we have reported a mouse model of tumor growth with paraparesis that may be used to assess novel therapeutic agents for ATL with CNS involvement.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
Objective:To compare the effect of L-asparaginase and pegaspargase in the treatment of adult acute lymphoblastic leukemia.Methods:In this study,96 patients who received treatment at the Shaanxi Provincial People’s Ho...Objective:To compare the effect of L-asparaginase and pegaspargase in the treatment of adult acute lymphoblastic leukemia.Methods:In this study,96 patients who received treatment at the Shaanxi Provincial People’s Hospital from April 2019 to April 2021 were selected.The control group received L-asparaginase treatment,and the observation group received pegaspargase treatment.The curative effect and adverse reaction rate were compared between the two groups.Results:Comparing the experimental statistical results of the observation and the control groups,it can be concluded that the effect of the former group is better than that of the latter group in terms of clinical curative effect and statistics of adverse reactions.Conclusion:In the treatment of adult acute lymphoblastic leukemia,the application of pegaspargase therapy has a significantly better clinical effect and is worthy of further promotion.展开更多
Adult T-cell leukemia/lymphoma(ATLL)is an aggressive peripheral T-cell lymphoma caused by the human T lymphotropic virus type-1.The skin is affected in approximately half of ATLL patients,and skin lesions may be the f...Adult T-cell leukemia/lymphoma(ATLL)is an aggressive peripheral T-cell lymphoma caused by the human T lymphotropic virus type-1.The skin is affected in approximately half of ATLL patients,and skin lesions may be the first manifestation of the disease.The skin lesions of ATLL are polymorphous,and depend on the type of skin eruption,which makes it possible for doctors to predict the prognosis of the disease based on the characteristics of skin lesions.In this review article,we describe the clinical manifestations and histopathological patterns of skin lesions in ATLL,focus on its diagnostic and prognostic significance,and also summarize the advances in the treatment of ATLL.展开更多
Objective To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia (T-ALL) cells and potential molecular mechanisms. Methods The anti-proliferation effect of resve...Objective To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia (T-ALL) cells and potential molecular mechanisms. Methods The anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MTI- test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK. Results Resveratrol inhibited the proliferation and dose and time-dependent manner. It also induced cyclin-dependent kinase (CDK) inhibitors p21 and induced apoptosis and autophagy in T-ALL cells in a cell cycle arrest at G0/G1 phase via up regulating p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins (Mcl-1 and Bcl-2) and increased the expression of proapoptotic proteins (Bax, Bim, and Bad), and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-11/LC3-1 and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced. Conclusion Our findings have suggested that resveratrol induces cell cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting Akt/mTOR/p7OS6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL.展开更多
Ikaros is a zinc finger transcriptional regulator encoded by the Ikzf1 gene.Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemi...Ikaros is a zinc finger transcriptional regulator encoded by the Ikzf1 gene.Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemia.In particular,Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia.Its role in T-cell leukemia,however,has been more controversial.While Ikaros deficiency appears to be very frequent in murine T-cell leukemias,loss of Ikaros appears to be rare in human T-cell acute lymphoblastic leukemia (T-ALL).We review here the evidence linking Ikaros to T-ALL in mouse and human systems.展开更多
T-cell acute lymphoblastic leukemia(T-ALL)is a hematological tumor caused by the malignant transformation of immature T-cell progenitor cells.Emerging studies have stated that microRNAs(miRNAs)may play key roles in T-...T-cell acute lymphoblastic leukemia(T-ALL)is a hematological tumor caused by the malignant transformation of immature T-cell progenitor cells.Emerging studies have stated that microRNAs(miRNAs)may play key roles in T-ALL progression.This study aimed to investigate the roles of miR-145-3p in T-ALL cell proliferation,invasion,and apoptosis with the involvement of the nuclear factor-kappaB(NF-κB)signaling pathway.T-ALL Jurkat cells were harvested,and the expression of miR-145-3p and NF-κB-p65 was measured.Gain-and loss-of-functions of miR-145-3p and NF-κB-p65 were performed to identify their roles in the biological behaviors of Jurkat cells,including proliferation,apoptosis,and invasion.Consequently,the current study demonstrated that miR-145-3p was down-regulated while NF-κB-p65 was up-regulated in Jurkat cells.miR-145-3p directly bound to the 3’untranslated region of NF-κB-p65.Over-expression of miR-145-3p inhibited Jurkat cell proliferation,invasion,and resistance to apoptosis,while over-expression of NF-κB-p65 presented opposite trends.Co-transfection of miR-145-3p and NF-κB-p65 promoted the malignant behaviors of Jurkat cells compared to miR-145-3p transfection alone,while it reduced these behaviors of Jurkat cells compared to NF-κB-p65 transfection alone.Taken together,this study provided evidence that miR-145-3p could suppress proliferation,invasion,and resistance to the death of T-ALL cells via inactivating the NF-κB signaling pathway.展开更多
We performed a retrospective analysis to investigate dynamic peri-hematopoieticstem cell transplantation(HSCT)minimal/measurable residual disease(MRD)on outcomes inpatients with T-cell acute lymphoblastic leukemia(T-A...We performed a retrospective analysis to investigate dynamic peri-hematopoieticstem cell transplantation(HSCT)minimal/measurable residual disease(MRD)on outcomes inpatients with T-cell acute lymphoblastic leukemia(T-ALL).A total of 271 patients were enrolledand classified into three groups:unchanged ncgative MRD pre-and post-HSCT group(group A),post-MRD non-increase group(group B),and post-MRD increase group(group C).The patientsin group B and group C experienced a higher cumulative incidence of relapse(CIR)(42%vs.71%vs.16%,P<0.001)and lower leukemia-free survival(LFS)(46%vs.21%vs.70%,P<0.001)andoverall survival(OS)(50%vs.28%vs.72%,P<0.001)than in group A,but there was no significantdifference in non-relapse mortality(NRM)among three groups(14%vs.12%vs.8%,P=0.752).Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR(HR=2.392,95%CI,1.816-3.151,P<0.001),LFS(HR=1.964,95%CI,1.546-2.496,P<0.001)and os(HR=1.731,95%CI,1.348-2.222,P<0.001).We also established a risk scoring system based ondynamic peri-HSCT MRD combined with remission status pre-HSCT and onsct of chronic graft-versus-host disease(GVHD).This risk scoring system could better distinguish ClR(c=0.730)thanthat for pre-HSCT MRD(c=0.562),post-HSCT MRD(c=0.616)and pre-and post-MRD dynamics(c=0.648).Our results confirm the outcome predictive value of dynamic peri-HSCT MRD eitheralone or in combination with other variables for patients with T-ALL.展开更多
BACKGROUND The development of peripheral T-cell lymphoma(PTCL)after chemotherapy for Hodgkin’s lymphoma(HL)is rare,and highly aggressive TCL/leukemia has not been reported to date.The relationship between HL and PTCL...BACKGROUND The development of peripheral T-cell lymphoma(PTCL)after chemotherapy for Hodgkin’s lymphoma(HL)is rare,and highly aggressive TCL/leukemia has not been reported to date.The relationship between HL and PTCL needs further exploration to understand the pathogenesis of metachronous lymphoma(ML)and find effective treatment options.We report a patient with ML,whose biopsy of a right cervical lymph node initially confirmed classical HL(CHL).CASE SUMMARY We report a patient with ML,whose biopsy of a right cervical lymph node initially confirmed CHL,with typical reed–sternberg cells expressing CD30 and PAX-5.T-cell leukemia/lymphoma occurred 3 years after treatment,and a lymph node biopsy at the onset confirmed PTCL,nonspecific type,expressing CD3,CD4 and CD8.The patient was treated with standard doses of chemotherapy,programmed cell death-ligand 1 monoclonal antibody,and chidamide,all of which failed to achieve complete remission.The patient was diagnosed with refractory state,and eventually died of leukocyte stasis.CONCLUSION The accuracy of the diagnosis needs to be confirmed when chemotherapeutic drugs are not effective.展开更多
A rare case of T cell acute lymphoblastic leukemia presenting with loss of vision, parotid swelling, hematuria and acute renal failure has been presented in a 40-year-old male. Acute T cell Lymphoblastic Leukemia shou...A rare case of T cell acute lymphoblastic leukemia presenting with loss of vision, parotid swelling, hematuria and acute renal failure has been presented in a 40-year-old male. Acute T cell Lymphoblastic Leukemia should also be kept in differential diagnosis of hematuria, acute renal failure and loss of vision.展开更多
BACKGROUND T-cell large granular lymphocytic leukemia(T-LGLL)is a rare type of aplastic anemia with diverse clinical manifestations.Concomitant diseases are often present at the first manifestation.We describe the tre...BACKGROUND T-cell large granular lymphocytic leukemia(T-LGLL)is a rare type of aplastic anemia with diverse clinical manifestations.Concomitant diseases are often present at the first manifestation.We describe the treatment of a patient with CD57-negativeγδT-LGLL with pure red cell aplasia(PRCA).CASE SUMMARY A 34-year-old woman with a 20-year history of anemia visited our hospital owing to severe dizziness and was admitted.Her condition was diagnosed as CD57-negativeγδT-LGLL with PRCA through bone marrow cytology,bone marrow pathology,bone marrow flow cytometry,bone marrow multiplex polymerase chain reaction combined with fluorescent fragment analysis,and other tests.Treatment with prednisone,methotrexate,and subcutaneous erythropoietin did not significantly change her hemoglobin level.After treatment with oral cyclophosphamide for 3 mo,her hemoglobin level increased to approximately 100 g/L.After 5 mo of treatment,the patient could perform activities of daily living independently.CONCLUSION The treatment of CD57-negativeγδT-LGLL with PRCA with cyclophosphamide helps to improve prognosis.展开更多
BACKGROUND Multiple primary cancer refers to more than one synchronous or sequential cancer in the same individual.Multiple primary cancer always presents as solid cancer or acute myeloid leukemia(AML)secondary to lym...BACKGROUND Multiple primary cancer refers to more than one synchronous or sequential cancer in the same individual.Multiple primary cancer always presents as solid cancer or acute myeloid leukemia(AML)secondary to lymphoma.Here,we report a rare case of secondary peripheral T-cell lymphoma and AML after Burkitt lymphoma treatment.CASE SUMMARY A 54-year-old female patient was admitted to our hospital complaining of edema on her left lower limb.Physical examination revealed multiple superficial lymphadenectasis on her neck and pelvis.Color ultrasonography examination showed multiple uterine fibroids and a solid mass at the lower left side of the abdomen.Pathological biopsy revealed Burkitt lymphoma.After three hyper-CVAD(A+B)regimens,she achieved complete remission.Two years later,lymphadenectasis reoccurred.A relevant biopsy confirmed the diagnosis of peripheral T-cell lymphoma,which was accompanied by gastrointestinal invasion and hemocytopenia.Meanwhile,bone marrow examination revealed AML.On the second day of scheduled treatment,she developed gastrointestinal bleeding,peptic ulcers,and hemorrhagic shock and was critically ill.She was then discharged from the hospital due to financial concerns.CONCLUSION This is the first report of secondary peripheral T-cell lymphoma and AML after Burkitt lymphoma treatment with heterochronous and synchronal multiple primary cancers.展开更多
T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell progenitors.The development of targeted therapeutic regimens is impeded by poo...T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell progenitors.The development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this disease.In this study,we performed multi-omics integration analysis,which included mRNA expression,chromatin accessibility,and gene-dependency database analyses,to identify potential stage-specific druggable targets and repositioned drugs for this disease.This multi-omics integration helped identify 29 potential pathological genes for T-ALL.These genes exhibited tissue-specific expression profiles and were enriched in the cell cycle,hematopoietic stem cell differentiation,and the AMPK signaling pathway.Of these,four known druggable targets(CDK6,TUBA1A,TUBB,and TYMS)showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in T-ALL.The TUBA1A expression level was higher in the early T cell precursor(ETP)-ALL cells,while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive stage.CDK6 exhibited a U-shaped expression pattern in malignant T cells along the naıve to maturation stages.Furthermore,mebendazole and gemcitabine,which target TUBA1A and TYMS,respectively,exerted stage-specific inhibitory effects on T-ALL cell lines,indicating their potential stage-specific antileukemic role in T-ALL.Collectively,our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.展开更多
Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role ...Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy.Common MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGS),and each method has advantages and limitations.It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse.Thus,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice.This review assesses the common and novel MRD assessment methods.In addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HSCT),as well as other therapeutic strategies to improve treatment effect.Furthermore,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.展开更多
文摘Multiple lymphomatous polyposis (MLP) is an unusual form of non-Hodgkin's lymphoma characterized by polyps throughout the gastrointestinal tract. It has been reported that most MLP are observed in cases with mantle cell lymphoma of B-cell type. We herein present a case of a 66-year-old man with adult T-cell leukemia/lymphoma (ATLL). Colonoscopy revealed MLP throughout the colon and histopathological findings of ATLL cell infiltration. The patient died despite combination of chemotherapy. The literature of manifestations of colonic involvement of ATLL isreviewed and the importance of endoscopic evaluation to differentiate ATLL intestinal lesions from opportunistic infectious enterocolitis is discussed.
文摘Tuberculosis (TB) is a major public health problem worldwide and a large number of fatal cases are still reported. Immunocompetent individuals are naturally susceptible to TB, and immunocompromised patients have a greater risk of infection. Although patients with adult T-cell leukemia/lymphoma (ATL) are in an immunosuppressed condition, there is only one reported case of TB accompanied with ATL in the English- language literature in the field of dermatology. Here, we report two patients with chronic-type ATL infected with TB manifesting as cutaneous solitary masses. Case 1 was a 58-year-old woman diagnosed with lumbar abscess with pulmonary TB. Case 2 was an 84-year-old woman diagnosed with tuberculous lymphadenitis in the left cervical region. It is important to raise the differential diagnosis of TB and perform tissue culture for acid-fast bacilli as well as Interferon-Gamma release assay test when dermatologists encounter mass lesions in patients with ATL.
基金Japan Leukemia Research FundGrant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science,Grant/Award Number:No.24500493
文摘Adult T-cell leukemia( ATL) is a mature T-cell malignancy caused by human T-cell leukemia virus type I infection, and 10%-25% of patients show central nervous system( CNS) involvement. CNS involvement significantly reduces survival and there are no effective treatments for CNS involvement. Therefore, an appropriate animal model is required to evaluate the inhibitory effects of novel drugs on the progression of ATL with CNS involvement. Here, we established a mouse model of ATL with CNS involvement using NOD.Cg-Prkdc~ (scid) Il2 rg ^(tm1Wjl)/SzJ mice inoculated with ATL cells intramuscularly in the postauricular region, and these mice showed paraparesis. Of the 10 mice inoculated with ATL cells intramuscularly(I.M.) at 5 weeks of age, 8(80%) showed paraparesis, whereas none of the 10 mice inoculated with ATL cells subcutaneously(S.C.) showed paraparesis. In the I.M. group, PCR detected HTLV-1-specific genes in the thoracic and lumbar vertebrae; however, in the S.C. group, the vertebrae were negative for HTLV-1 genes. Histological analysis revealed a particularly high incidence of tumors, characterized by accumulation of the injected cells, in the thoracic vertebrae of mice in the I.M. group. Tumor cell infiltration was relatively high in the bone marrow. Spinal cord compression caused by invasion of the tumor mass outside the pia mater was observed in the thoracic vertebrae of the spinal cord. In conclusion, we have reported a mouse model of tumor growth with paraparesis that may be used to assess novel therapeutic agents for ATL with CNS involvement.
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.
文摘Objective:To compare the effect of L-asparaginase and pegaspargase in the treatment of adult acute lymphoblastic leukemia.Methods:In this study,96 patients who received treatment at the Shaanxi Provincial People’s Hospital from April 2019 to April 2021 were selected.The control group received L-asparaginase treatment,and the observation group received pegaspargase treatment.The curative effect and adverse reaction rate were compared between the two groups.Results:Comparing the experimental statistical results of the observation and the control groups,it can be concluded that the effect of the former group is better than that of the latter group in terms of clinical curative effect and statistics of adverse reactions.Conclusion:In the treatment of adult acute lymphoblastic leukemia,the application of pegaspargase therapy has a significantly better clinical effect and is worthy of further promotion.
基金The word was supported by the CAMS Innovation Fund for Medical Sciences(No.CIFMS-2017-I2M-1-017)PUMC Youth Fund(No.3332017168).
文摘Adult T-cell leukemia/lymphoma(ATLL)is an aggressive peripheral T-cell lymphoma caused by the human T lymphotropic virus type-1.The skin is affected in approximately half of ATLL patients,and skin lesions may be the first manifestation of the disease.The skin lesions of ATLL are polymorphous,and depend on the type of skin eruption,which makes it possible for doctors to predict the prognosis of the disease based on the characteristics of skin lesions.In this review article,we describe the clinical manifestations and histopathological patterns of skin lesions in ATLL,focus on its diagnostic and prognostic significance,and also summarize the advances in the treatment of ATLL.
基金supported by grants from the Department of Science and Technology of Sichuan Province,China (No.2008JY0029-1 and No.07FG002-024)research funds from the Program for Changjiang Scholars and Innovative-Research Team in University (No.IRT0935)
文摘Objective To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia (T-ALL) cells and potential molecular mechanisms. Methods The anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MTI- test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK. Results Resveratrol inhibited the proliferation and dose and time-dependent manner. It also induced cyclin-dependent kinase (CDK) inhibitors p21 and induced apoptosis and autophagy in T-ALL cells in a cell cycle arrest at G0/G1 phase via up regulating p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins (Mcl-1 and Bcl-2) and increased the expression of proapoptotic proteins (Bax, Bim, and Bad), and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-11/LC3-1 and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced. Conclusion Our findings have suggested that resveratrol induces cell cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting Akt/mTOR/p7OS6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL.
基金Supported by Institut National du Cancer,La Ligue Contre le Cancer (équipe labellisée),l’Agence Nationale de la Recherche,l’Association pour la Recherche sur le Cancer and La Fondation de France,with institute funding from INSERM,CNRS and l’ Université de Strasbourg
文摘Ikaros is a zinc finger transcriptional regulator encoded by the Ikzf1 gene.Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemia.In particular,Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia.Its role in T-cell leukemia,however,has been more controversial.While Ikaros deficiency appears to be very frequent in murine T-cell leukemias,loss of Ikaros appears to be rare in human T-cell acute lymphoblastic leukemia (T-ALL).We review here the evidence linking Ikaros to T-ALL in mouse and human systems.
文摘T-cell acute lymphoblastic leukemia(T-ALL)is a hematological tumor caused by the malignant transformation of immature T-cell progenitor cells.Emerging studies have stated that microRNAs(miRNAs)may play key roles in T-ALL progression.This study aimed to investigate the roles of miR-145-3p in T-ALL cell proliferation,invasion,and apoptosis with the involvement of the nuclear factor-kappaB(NF-κB)signaling pathway.T-ALL Jurkat cells were harvested,and the expression of miR-145-3p and NF-κB-p65 was measured.Gain-and loss-of-functions of miR-145-3p and NF-κB-p65 were performed to identify their roles in the biological behaviors of Jurkat cells,including proliferation,apoptosis,and invasion.Consequently,the current study demonstrated that miR-145-3p was down-regulated while NF-κB-p65 was up-regulated in Jurkat cells.miR-145-3p directly bound to the 3’untranslated region of NF-κB-p65.Over-expression of miR-145-3p inhibited Jurkat cell proliferation,invasion,and resistance to apoptosis,while over-expression of NF-κB-p65 presented opposite trends.Co-transfection of miR-145-3p and NF-κB-p65 promoted the malignant behaviors of Jurkat cells compared to miR-145-3p transfection alone,while it reduced these behaviors of Jurkat cells compared to NF-κB-p65 transfection alone.Taken together,this study provided evidence that miR-145-3p could suppress proliferation,invasion,and resistance to the death of T-ALL cells via inactivating the NF-κB signaling pathway.
基金the Beijing Municipal Science and Technology Commission(No.Z181100009618032)the National Natural Science Foundation of China(Nos.:81870141,82070185,81670186).
文摘We performed a retrospective analysis to investigate dynamic peri-hematopoieticstem cell transplantation(HSCT)minimal/measurable residual disease(MRD)on outcomes inpatients with T-cell acute lymphoblastic leukemia(T-ALL).A total of 271 patients were enrolledand classified into three groups:unchanged ncgative MRD pre-and post-HSCT group(group A),post-MRD non-increase group(group B),and post-MRD increase group(group C).The patientsin group B and group C experienced a higher cumulative incidence of relapse(CIR)(42%vs.71%vs.16%,P<0.001)and lower leukemia-free survival(LFS)(46%vs.21%vs.70%,P<0.001)andoverall survival(OS)(50%vs.28%vs.72%,P<0.001)than in group A,but there was no significantdifference in non-relapse mortality(NRM)among three groups(14%vs.12%vs.8%,P=0.752).Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR(HR=2.392,95%CI,1.816-3.151,P<0.001),LFS(HR=1.964,95%CI,1.546-2.496,P<0.001)and os(HR=1.731,95%CI,1.348-2.222,P<0.001).We also established a risk scoring system based ondynamic peri-HSCT MRD combined with remission status pre-HSCT and onsct of chronic graft-versus-host disease(GVHD).This risk scoring system could better distinguish ClR(c=0.730)thanthat for pre-HSCT MRD(c=0.562),post-HSCT MRD(c=0.616)and pre-and post-MRD dynamics(c=0.648).Our results confirm the outcome predictive value of dynamic peri-HSCT MRD eitheralone or in combination with other variables for patients with T-ALL.
文摘BACKGROUND The development of peripheral T-cell lymphoma(PTCL)after chemotherapy for Hodgkin’s lymphoma(HL)is rare,and highly aggressive TCL/leukemia has not been reported to date.The relationship between HL and PTCL needs further exploration to understand the pathogenesis of metachronous lymphoma(ML)and find effective treatment options.We report a patient with ML,whose biopsy of a right cervical lymph node initially confirmed classical HL(CHL).CASE SUMMARY We report a patient with ML,whose biopsy of a right cervical lymph node initially confirmed CHL,with typical reed–sternberg cells expressing CD30 and PAX-5.T-cell leukemia/lymphoma occurred 3 years after treatment,and a lymph node biopsy at the onset confirmed PTCL,nonspecific type,expressing CD3,CD4 and CD8.The patient was treated with standard doses of chemotherapy,programmed cell death-ligand 1 monoclonal antibody,and chidamide,all of which failed to achieve complete remission.The patient was diagnosed with refractory state,and eventually died of leukocyte stasis.CONCLUSION The accuracy of the diagnosis needs to be confirmed when chemotherapeutic drugs are not effective.
文摘A rare case of T cell acute lymphoblastic leukemia presenting with loss of vision, parotid swelling, hematuria and acute renal failure has been presented in a 40-year-old male. Acute T cell Lymphoblastic Leukemia should also be kept in differential diagnosis of hematuria, acute renal failure and loss of vision.
基金Supported by Xiamen Medical and Health Guidance Project,No.3502Z20199137Fujian Medical and Health Training Project for Young and Middle-aged Backbone Talents,No.2020GGB068Educational and Scientific Research Program for Young and Middle-Aged Teachers of Fujian Province,No.JAT190838.
文摘BACKGROUND T-cell large granular lymphocytic leukemia(T-LGLL)is a rare type of aplastic anemia with diverse clinical manifestations.Concomitant diseases are often present at the first manifestation.We describe the treatment of a patient with CD57-negativeγδT-LGLL with pure red cell aplasia(PRCA).CASE SUMMARY A 34-year-old woman with a 20-year history of anemia visited our hospital owing to severe dizziness and was admitted.Her condition was diagnosed as CD57-negativeγδT-LGLL with PRCA through bone marrow cytology,bone marrow pathology,bone marrow flow cytometry,bone marrow multiplex polymerase chain reaction combined with fluorescent fragment analysis,and other tests.Treatment with prednisone,methotrexate,and subcutaneous erythropoietin did not significantly change her hemoglobin level.After treatment with oral cyclophosphamide for 3 mo,her hemoglobin level increased to approximately 100 g/L.After 5 mo of treatment,the patient could perform activities of daily living independently.CONCLUSION The treatment of CD57-negativeγδT-LGLL with PRCA with cyclophosphamide helps to improve prognosis.
基金Medical and Health Research Project of Hainan Province,No.20A200013.
文摘BACKGROUND Multiple primary cancer refers to more than one synchronous or sequential cancer in the same individual.Multiple primary cancer always presents as solid cancer or acute myeloid leukemia(AML)secondary to lymphoma.Here,we report a rare case of secondary peripheral T-cell lymphoma and AML after Burkitt lymphoma treatment.CASE SUMMARY A 54-year-old female patient was admitted to our hospital complaining of edema on her left lower limb.Physical examination revealed multiple superficial lymphadenectasis on her neck and pelvis.Color ultrasonography examination showed multiple uterine fibroids and a solid mass at the lower left side of the abdomen.Pathological biopsy revealed Burkitt lymphoma.After three hyper-CVAD(A+B)regimens,she achieved complete remission.Two years later,lymphadenectasis reoccurred.A relevant biopsy confirmed the diagnosis of peripheral T-cell lymphoma,which was accompanied by gastrointestinal invasion and hemocytopenia.Meanwhile,bone marrow examination revealed AML.On the second day of scheduled treatment,she developed gastrointestinal bleeding,peptic ulcers,and hemorrhagic shock and was critically ill.She was then discharged from the hospital due to financial concerns.CONCLUSION This is the first report of secondary peripheral T-cell lymphoma and AML after Burkitt lymphoma treatment with heterochronous and synchronal multiple primary cancers.
基金the National Natural Science Foundation of China(No.82070167,81870126,81900190,81802803)The Chongqing Science and Technology Bureau Major Project,Chongqing,China(No.cstc2020jcyjmsxmX0782).
文摘T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell progenitors.The development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this disease.In this study,we performed multi-omics integration analysis,which included mRNA expression,chromatin accessibility,and gene-dependency database analyses,to identify potential stage-specific druggable targets and repositioned drugs for this disease.This multi-omics integration helped identify 29 potential pathological genes for T-ALL.These genes exhibited tissue-specific expression profiles and were enriched in the cell cycle,hematopoietic stem cell differentiation,and the AMPK signaling pathway.Of these,four known druggable targets(CDK6,TUBA1A,TUBB,and TYMS)showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in T-ALL.The TUBA1A expression level was higher in the early T cell precursor(ETP)-ALL cells,while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive stage.CDK6 exhibited a U-shaped expression pattern in malignant T cells along the naıve to maturation stages.Furthermore,mebendazole and gemcitabine,which target TUBA1A and TYMS,respectively,exerted stage-specific inhibitory effects on T-ALL cell lines,indicating their potential stage-specific antileukemic role in T-ALL.Collectively,our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.
基金supported by grants from National Natural Science Foundation of China(Nos.81870140 and 82070184)Peking University People’s Hospital Research and Development Funds(No.RDL2021-01)+1 种基金Beijing Nova Program(No.20220484235)Beijing Life Oasis Public Service Center(No.CARTFR-01)
文摘Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy.Common MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGS),and each method has advantages and limitations.It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse.Thus,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice.This review assesses the common and novel MRD assessment methods.In addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HSCT),as well as other therapeutic strategies to improve treatment effect.Furthermore,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.