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Objective: To compare the difference of the clinical and laboratory characteristics between γδ T-cell large granular lymphocyte leukemia (γδT-LGLL) and αβ T-cell large granular lymphocyte leukemia (αβT-LGLL) . Methods: The clinical and laboratory characteristics of 17 patients with γδT-LGLL and 91 patients with αβT-LGLL in the department of therapeutic center of anemia of enrolled in our hospital from January 2009 to January 2019 were retrospectively analyzed. Results: The median age of the 17 patients with γδT-LGLL was 54 years (range, 25-73 years) , the most common presenting symptom was anemia. In comparison with αβT-LGLL patients, splenomegaly was common (41% and 44%, respectively) , whereas hepatomegaly (12% and 5%, respectively) and lymphadenopathy (6% and 8%, respectively) were rare. The positive rates of antinuclear antibody (59% and 45%, respectively) were high, whereas the positive rates of rheumatoid factor (6% and 10%, respectively) were rare for both groups. There were no differences on peripheral blood counts between the two groups. However, γδT-LGLL patients were found to be predominantly expressed a CD4(-)/CD8(-) phenotype. Steroid therapy with prednisone was used alone as first-line therapy for 1 patient. Cyclosporin A (CsA) was used alone as first-line therapy for 3 patients. CsA in combination with steroids were administered in 13 patients. After 4 months treatment, 2 patients acquired complete response, 4 patients acquired partial response, the overall response was 35%. Conclusion: γδT-LGLL is a rare mature T-lymphocyte proliferative disease. Clinical and laboratory characteristics were quite similar for γδT-LGLL in compare with αβT-LGLL. γδT-LGLL predominantly expressed a CD4(-)/CD8(-) phenotype. The data presented here indicate the CsA is an effective option for the first-line treatment of γδT-LGLL.
Subject(s)
Adult , Aged , Humans , Middle Aged , Leukemia, Large Granular Lymphocytic , Phenotype , Retrospective Studies , T-LymphocytesABSTRACT
Objective@#To compare the difference of the clinical and laboratory characteristics between γδ T-cell large granular lymphocyte leukemia (γδT-LGLL) and αβ T-cell large granular lymphocyte leukemia (αβT-LGLL) .@*Methods@#The clinical and laboratory characteristics of 17 patients with γδT-LGLL and 91 patients with αβT-LGLL in the department of therapeutic center of anemia of enrolled in our hospital from January 2009 to January 2019 were retrospectively analyzed.@*Results@#The median age of the 17 patients with γδT-LGLL was 54 years (range, 25-73 years) , the most common presenting symptom was anemia. In comparison with αβT-LGLL patients, splenomegaly was common (41% and 44%, respectively) , whereas hepatomegaly (12% and 5%, respectively) and lymphadenopathy (6% and 8%, respectively) were rare. The positive rates of antinuclear antibody (59% and 45%, respectively) were high, whereas the positive rates of rheumatoid factor (6% and 10%, respectively) were rare for both groups. There were no differences on peripheral blood counts between the two groups. However, γδT-LGLL patients were found to be predominantly expressed a CD4−/CD8− phenotype. Steroid therapy with prednisone was used alone as first-line therapy for 1 patient. Cyclosporin A (CsA) was used alone as first-line therapy for 3 patients. CsA in combination with steroids were administered in 13 patients. After 4 months treatment, 2 patients acquired complete response, 4 patients acquired partial response, the overall response was 35%.@*Conclusion@#γδT-LGLL is a rare mature T-lymphocyte proliferative disease. Clinical and laboratory characteristics were quite similar for γδT-LGLL in compare with αβT-LGLL. γδT-LGLL predominantly expressed a CD4−/CD8− phenotype. The data presented here indicate the CsA is an effective option for the first-line treatment of γδT-LGLL.
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Objective: To evaluate the clinical characteristics of T-cell acute leukemia/lymphoma (T-ALL) and explore the prognosis significance of early T-cell precursor leukemia/lymphoma. Methods: A cohort of 126 patients diagnosed with T-ALL from 2008 to 2014 in West China Hospital, Sichuan University were enrolled in this study. They were further categorized by immunophenotype according to the expression of T-cell lineage markers CD1a, CD8, CD5 and one or more stem cell or myeloid markers. The laboratory indicators and prognosis factors were also statistically analyzed. Results: Of all patients, the ratio of male to female was 2.5∶1, with the median age of 25 years old (range 14 to 77) . The percentage of ETP-ALL was up to 47.6%. T-ALL patients showed higher ratio in first clinical remission rate (CR(1)) than T-LBL ones (64.4% vs 30.8%, P=0.032) . Group with WBC count higher than 50×10(9)/L at presentation showed higher ration of achieving CR(1) than those lower than 50×10(9)/L (78.4% vs 50.9%, P=0.010) . In comparison with the non-ETP-ALL, ETP-ALL patients had older age of onset (P<0.001) , lower WBC count (P<0.001) , lower risk of CNS involvement (10.0% vs 30.2%, P=0.009) and slightly inferior overall survival (P=0.073) . T-cell lineage markers CD1a(-), CD8(-) and CD4(-) positive patients had higher CR(1) than their corresponding negative ones (P=0.002, P=0.000, P=0.001) , while CD33(-) and CD56(-) positive patients had lower ratio of achieving CR(1) than their negative ones, respectively (P=0.035, P=0.035) . Conclusion: Flow cytometry and associated markers for immunophenotyping was of significance in the diagnosis and prognosis monitoring of T-ALL/LBL. The percentage of ETP-ALL/LBL subtype was high in Chinese adolescent and adult T-ALL patients. ETP-ALL/LBL was a high risk subtype, which needs more precise standard for diagnosis and advanced therapies for better outcome.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , China , Immunophenotyping , Precursor Cells, T-Lymphoid/cytology , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , PrognosisABSTRACT
Objective@#To evaluate the clinical characteristics of T-cell acute leukemia/lymphoma (T-ALL) and explore the prognosis significance of early T-cell precursor leukemia/lymphoma.@*Methods@#A cohort of 126 patients diagnosed with T-ALL from 2008 to 2014 in West China Hospital, Sichuan University were enrolled in this study. They were further categorized by immunophenotype according to the expression of T-cell lineage markers CD1a, CD8, CD5 and one or more stem cell or myeloid markers. The laboratory indicators and prognosis factors were also statistically analyzed.@*Results@#Of all patients, the ratio of male to female was 2.5∶1, with the median age of 25 years old (range 14 to 77) . The percentage of ETP-ALL was up to 47.6%. T-ALL patients showed higher ratio in first clinical remission rate (CR1) than T-LBL ones (64.4% vs 30.8%, P=0.032) . Group with WBC count higher than 50×109/L at presentation showed higher ration of achieving CR1 than those lower than 50×109/L (78.4% vs 50.9%, P=0.010) . In comparison with the non-ETP-ALL, ETP-ALL patients had older age of onset (P<0.001) , lower WBC count (P<0.001) , lower risk of CNS involvement (10.0% vs 30.2%, P=0.009) and slightly inferior overall survival (P=0.073) . T-cell lineage markers CD1a-, CD8- and CD4- positive patients had higher CR1 than their corresponding negative ones (P=0.002, P=0.000, P=0.001) , while CD33- and CD56- positive patients had lower ratio of achieving CR1 than their negative ones, respectively (P=0.035, P=0.035) .@*Conclusion@#Flow cytometry and associated markers for immunophenotyping was of significance in the diagnosis and prognosis monitoring of T-ALL/LBL. The percentage of ETP-ALL/LBL subtype was high in Chinese adolescent and adult T-ALL patients. ETP-ALL/LBL was a high risk subtype, which needs more precise standard for diagnosis and advanced therapies for better outcome.
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Objective@#To detect the characteristics of phosphatase and tensin homolog (PTEN) mutations in adult T-cell acute lymphoblastic leukemia (T-ALL) and its relationship with the prognosis.@*Methods@#Fifty-five adult T-ALL patients were enrolled in Jiangsu Province Hospital from February 2010 to April 2016. Mononuclear bone marrow cells were extracted by using Ficoll density gradient centrifugation. Genomic DNA was extracted from isolated mononuclear cells. Amplified exon 1-9 of PTEN by polymerase chain reaction (PCR) specifically amplified PTEN exon, then DNA was purified, sequenced and compared. The mutation occurrence rate, mutation types, and the relations with several clinical indicators were analyzed.@*Results@#PTEN mutations were detected in 5 patients, and 8 types of mutations were detected in 55 T-ALL patients with mutation rate of 9.1% (5/55). All the mutations were located in exon 7 of the genes. Five patients with PTEN mutations also merged other gene mutations like NOTCH1 and DNM2. The level of median lactate dehydrogenase (LDH) in patients with PTEN mutations was higher than that in patients without PTEN mutations (3 358 U/L vs. 755 U/L, Z=-2.014, P= 0.044). No significant differences were found in gender, age, white blood count, hemoglobin, platelet count, overall survival rate, event free survival, recurrence free survival between the two groups (P > 0.05).@*Conclusion@#PTEN is a tumor suppressor gene, and its mutation plays a significant role in the occurrence and development of adult T-ALL patients, which may be associated with the poor prognosis.
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Objective@#To analyze whether heat-shock protein 90 (HSP90) be involved in a permanently abnormal activated JAK/STAT signaling in ATL cells in vitro.@*Methods@#The effect of 17-AAG on proliferation of ATL cell lines HUT-102 was assessed using CCK8 at different time points. Cell apoptosis was measured by flow cytometry. The specific proteins HSP90, STAT5, p-STAT5 and JAK3 were detected by Western blotting.@*Results@#Overexpression of HSP90 in HUT-102 cell lines was disclosed (P<0.05) , and constitutive activation of JAK3/STAT5 signaling was observed in HTLV-1-infected T-cell lines but not in normal PBMCs; Treatment of ATL cell lines with 17-AAG led to reduced cell proliferation, but there was no significant change in terms of cell proliferation when the concentration of 17-AAG between 2 000-8 000 nmol/L (P>0.05) . 17-AAG induced cell apoptosis in different time-points and concentrations. 17-AAG don’t affect the expression of JAK3 gene.@*Conclusion@#This study indicated that JAK3 as HSP90 client protein was aberrantly activated in HTLV-1-infected T-cell lines, leading to constitutive activation of p-STAT5 in JAK/STAT signal pathway, which demonstrated that HSP90-inhibitors 17-AAG inhibited the growth of HTLV-1-infected T-cell lines by reducing cell proliferation and inducing cell apoptosis.
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La leucemia/linfoma de células T del adulto ( Adult T-Cell Leukemia/Lymphoma , ATLL) es una neoplasia maligna de los linfocitos T CD4 maduros, que resulta de la infección con el virus T-linfotrópico humano de tipo 1 (HTLV-1), con varias manifestaciones sistémicas y cutáneas. Se presentan dos casos de leucemia/linfoma de células T del adulto en pacientes del suroccidente de Colombia, cuyos diagnósticos fueron confirmados por histología, inmunohistoquímica, citometría de flujo y pruebas ELISA y Western blot. También, se discute acerca del virus y cómo hacer el diagnóstico en países como el nuestro.
Adult T-cell leukemia/lymphoma (ATLL) is a malignant neoplasia of mature CD4+ T lymphocytes,resulting from infection with human T-lymphotropic virus type 1 (HTLV-1), with several systemic and cutaneous manifestations. We present two cases of adult T-cell leukemia/lymphoma, in patients from the Colombian Southwestern region, whose diagnoses were confirmed by histology, immunohistochemistry, flow cytometry, ELISA and Western blot tests. We also discuss about the virus and how to make this diagnosis in countries like Colombia.
Subject(s)
Aged , Female , Humans , Middle Aged , Leukemia-Lymphoma, Adult T-Cell/diagnosis , ColombiaABSTRACT
T-cell acute lymphoblastic leukemia (T-ALL) is one of the most common types of leukemia in children. With over 50 ％ of activating Notch1mutations in T-ALL,identification of activating Notch1mutations has brought interest toward targeting the Notch signaling pathway in this disease.Small-molecule γ-secretase inhibitors (GSI) can block a critical proteolytic step required for Notch1activation,but the clinical application of GSI has been hindered. Therefore, new therapeutic strategies aim to design of effective antiNotch1therapies in T-ALL are needed, including combination therapies with molecularly targeted drugs and glucocorticoids. This review put emphasis on the molecular basis of Notch1, the mechanisms of action of oncogenic Notch1and clinical significance of Notch 1mutations in T-ALL.
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Notch signaling can control T cell development and differentiation and lead to acute T cell lymphoma/leukemia (T-ALL). Most Notch1mutations in human T-ALL are the HD domain and the PEST domain. Aberrant Notch1activation can induce T-ALL by PI3K/Akt, mTOR or/and NF-κB pathways. Some recent reports suggested that Notch signaling could not only control T cell development,but also has a role in acute myeloid leukemia (AML) and Graft-versus-host Disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Moreover,Notch signaling can regulate the expansion of HSC as well as generate increased numbers of progenitor cells which are capable of rapid repopulation to improve HSC homeostasis and hematopoietic recovery after allo-HSCT.
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Objective To investigate the expression of FBXW7 during the development of Notch1induced murine leukemia.Methods Notch1 over-expressing murine model of T-cell acute lymphoblastic leukemia was used to study the expression of FBXW7 by real-time PCR methods.Bone marrow mononuclear cells (BMNC) were isolated on different days after transplantation and CD45.2+ GFP+ leukemia cells were sorted by flow cytometry at late stage.The expression changes of FBXW7 were tested by real-time PCR.Results The mouse bone marrow cells both from leukemia and control groups expressed FBXW7.Different expression patterns of FBXW7 were observed during the development of leukemia. The expression of FBXW7 was gradually increased in control group, whereas the expression level of FBXW7 in leukemia group was decreased steadily and reached one-sixth of that in control group on 12th day.Furthermore,lower expression level of FBXW7 was observed in CD45+.2 GFP+ leukemia cells.Conclusion Decreased expression of FBXW7 is observed in Notch1-induced mouse leukemia model,suggesting that the abnormal ubiquitin degradation pathway mediated by FBXW7 might contribute to the leukemogenesis in Notch1-induced murine leukemia model.
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Objective To observe the effects of triptolide(TPL) on the anti-oncogene-APC gene of acute lymphoblastic leukemia cell line Jurkat in vitro. Methods The effects of TPL on proliferation Jurkat cells were assayed by using cell culture, MTT. The effects of TPL on APC gene of Jurkat cells were analyzed by nested methylation specific PCR and RT-PCR. The effects of TPL on the proteinum expression of APC gene were detected by Western blotting analysis. Results Following the treatment of TPL, the cell proliferation rate was degraded as the treatment concentration increased and the culture time extended. The effects were dose and time-dependent. The 48 hour IC50 was 19.7 ng/ml. TPL can reverse hypermethylation of APC gene,and induce the expression of the mRNA and the proteinum. Conclusion Low dose TPL could depress the proliferation rate of Jurkat. The possible mechanism might be its reversing the hypermethylation of APC gene and activiting the expression of APC gene.
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Objective To explore the CD38 expression in T-cens(CD38-T)of chronic lymphocytic leukemia(CLL).Methods Multi-parameter flow cytometry was used to detect the expression of CD38,ZAP-70 and CD4/CD8 in 83 CLL patients.Results CD38 was positively expressed in 49.4%(41/83)T-cells(CD38-T)and 50.6%(42/83)tumor cells(CD38-B)of all CLL patients.The expression of the CD38-T was highly correlated with CD38-B(r=0.553,P＜0.01).ZAP-70+CD38+-T and ZAP-70-CD38-T constituted 67.5%(56/83)of CLL patients.There was significant correlation between CD38-T and ZAP-70 (r=0.349,P＜0.01).There was 33.3%(14/42)patients with CD38-T in Binet A patients,and 65.9% (27/41)in Binet B+C patients.There was also significant correlation between CD38-T and Binet B+C(r=0.312,P＜0.05),and CD4/CD8(r=0.453,P＜0.05).Conclusions Aberrant expression of CD38 in T-cells might be of prognostic relevance in CLL Most of the patients with high level CD38-T expression are accompanied with disorder or imbalance of immune function.CD38 expression in T cells might be a new prognostic factor in CLL.
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AIM: To study the effect of IL-12 on T lymphocytes apoptosis, the expression of Fas/FasL and TNFR/TNF?. METHODS: Terminal dUTP nick end labeling(TUNEL) and Annexin V assay were used. Anti-TNFR were labeled with FITC, anti-CD95 was labeled with PE and Anti-FasL with biotin. Three kinds of T cells (HTB176,TIB152 and human normal T cells) were analysed through flow cytometry. RESULTS: At 1st hour after being treated with IL-12, the expression of FasL protein and FasL mRNA in HTB176 and TIB152 began to increase and reached peak value in 24 hours. In the normal T cells, FasL just began to increase in 1 hour and maintained stability in 6, 12 and 24 hours through the later experiment period. All three kinds of T cells displayed no change in the expression of CD95 and TNFR/TNF? under the stimulation of IL-12. CONCLUSION: Expression of such apoptosis regulating factors were different in the apoptosis of T cells induced by IL-12.