scholarly journals Evolution of T-cell clonality in a patient with Ph-negative acute lymphocytic leukemia occurring after interferon and imatinib therapy for Ph-positive chronic myeloid leukemia

2010 ◽  
Vol 3 (1) ◽  
pp. 14 ◽  
Author(s):  
Liang Wang ◽  
Kanger Zhu ◽  
Xianfeng Zha ◽  
Shaohua Chen ◽  
Lijian Yang ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Imatinib Therapy ◽  
T Cell Clonality ◽  
Cell Clonality

scholarly journals Comparison of somatic STAT3 and STAT5b gene mutations between Felty's syndrome and T-cell large granular lymphocytic leukemia with rheumatoid arthritis

2020 ◽  
Author(s):  
Vadim R. Gorodetskiy ◽  
Yulia V. Sidorova ◽  
Natalia A. Kupryshina ◽  
Vladimir I. Vasilyev ◽  
Natalya A. Probatova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Somatic Mutations ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Felty's Syndrome ◽  
Large Granular Lymphocytic Leukemia ◽  
Felty’S Syndrome ◽  
T Cell Clonality ◽  
Cell Clonality

Abstract Objectives Approximately 15% of patients with T-cell large granular lymphocytic leukemia (T-LGLL) have rheumatoid arthritis (RA). RA-associated T-LGLL with low large granular lymphocyte counts (aleukemic presentation) and Felty's syndrome (FS) have indistinguishable clinical presentations. These disorders are distinguished by T-cell clonality which is observed in T-LGLL but not in FS. Activating somatic mutations in the signal transducer and activator of transcription 3 (STAT3) and 5 (STAT5b) genes are involved in T-LGLL pathogenesis; however, the prevalence of these mutations in FS is unknown.Methods Based on the rearrangements of T-cell receptor (TCR) gamma and beta genes according to the BIOMED-2 protocol, we examined T-cell clonality in 81 patients with RA and unexplained neutropenia. We stratified these patients by the presence or absence of T-cell clonality, respectively, into 2 groups: RA-associated T-LGLL (56 patients) and FS (25 patients). Allele-specific TaqMan Real-Time polymerase chain reaction assay was employed to detect point somatic mutations in STAT3 and STAT5b genes in each group.Results Mutations of the STAT3 gene were detected in none of the 24 cases of FS and in 22 of 56 cases of RA-associated T-LGLL (39%) (p < 0.001). No mutation of the STAT5b gene was detected in any of the patients in each group.Conclusions Although further data are needed, our results suggest that activating somatic mutations in STAT3 and STAT5b genes are not involved in the pathogenesis of FS.

scholarly journals Analysis of a single-institution cohort of patients with Felty's syndrome and T-cell large granular lymphocytic leukemia in the setting of rheumatoid arthritis

2020 ◽  
Author(s):  
Vadim Romanovich Gorodetskiy ◽  
Yulia Vladimirovna Sidorova ◽  
Natalia Alexandrovna Kupryshina ◽  
Vladimir Ivanovich Vasilyev ◽  
Natalya Alexandrovna Probatova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Laboratory Data ◽  
Gene Mutations ◽  
Lymphocytic Leukemia ◽  
Felty's Syndrome ◽  
Large Granular Lymphocytic Leukemia ◽  
Felty’S Syndrome ◽  
T Cell Clonality ◽  
Cell Clonality

AbstractT-cell large granular lymphocytic leukemia (T-LGLL) is a lymphoproliferative disorder characterized by a persistent increase in the number of large granular lymphocytes (LGLs), neutropenia, and splenomegaly. Clinical manifestations of T-LGLL in the setting of rheumatoid arthritis (RA) are often identical to those in which one would suspect Felty's syndrome (FS). These disorders are distinguished by the presence of T-cell clonality, which is present in T-LGLL but not in FS. Mutations in the signal transducer and activator of transcription 3 (STAT3) and 5b (STAT5b) genes can be used as molecular markers of T-LGLL, but their prevalence in FS is unknown.Eighty-one patients with RA and unexplained neutropenia or/and an increase in the number of LGLs above 2 × 109/L were stratified into RA-associated T-LGLL (N = 56) or FS (N = 25) groups based on the presence or absence of T-cell clonality. STAT3 and STAT5b gene mutations were assessed in each group by means of allele-specific polymerase chain reaction assays. Clinical, immunological, laboratory data and the results of immunophenotyping of blood and bone marrow lymphocytes were also evaluated.Mutations of the STAT3 gene and an increase in the number of LGLs above 2 × 109/L were detected in RA-associated T-LGLL, but not in FS (39% vs 0% and 21% vs 0%, respectively). Mutations in the STAT5b gene were not observed in either group. Expression of CD57, CD16, and CD5−/dim on CD3+CD8+ T-lymphocytes was observed in both RA-associated T-LGLL and FS.STAT3 gene mutations or LGL counts over 2 × 109/L in RA patients are indicative of T-LGLL.

scholarly journals Renal tuberculosis in an imatinib-treated chronic myeloid leukemia

2020 ◽  
Vol 42 (3) ◽  
pp. 366-369
Author(s):  
Abhilash Chandra ◽  
Namrata Rao ◽  
Kiran Preet Malhotra
Keyword(s):  
T Cell ◽  
Chronic Myeloid Leukemia ◽  
T Cell Activation ◽  
Myeloid Leukemia ◽  
Cell Activation ◽  
Cell Function ◽  
Standard Form ◽  
Maintenance Phase ◽  
Imatinib Therapy ◽  
Renal Tuberculosis

ABSTRACT Imatinib, which inhibits tyrosine kinase activity of Bcr-Abl protein, is a standard form of treatment for chronic myeloid leukemia (CML). Through its immunomodulatory effect it affects T cell function in a number of ways. It inhibits antigen-induced T cell activation and proliferation. Antigen-specific T-cells and macrophages are vital for protection against Mycobacterium tuberculosis. Here we present a case of renal tuberculosis associated with imatinib therapy in the maintenance phase of CML. With granulomatous interstitial nephritis and positive tubercular DNA on renal biopsy, the condition was successfully treated with anti-tubercular therapy. This case provides support to the hypothesis that imatinib therapy in CML increases the susceptibility to tuberculosis and strict vigilance is required to enable its early detection and treatment.

scholarly journals Spectrum of benign and malignant hematological diseases diagnosed in Quetta on bone marrow aspiration.

2020 ◽  
Vol 27 (03) ◽  
pp. 641-645
Author(s):  
Ayesha Samad Dogar ◽  
Tariq Mehmood Marri ◽  
Tariq Mehmood Marri ◽  
Hafiz Ather Farooq
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Aplastic Anemia ◽  
Myeloid Leukemia ◽  
Acute Lymphocytic Leukemia ◽  
Megaloblastic Anemia ◽  
Bone Marrow Aspiration ◽  
Lymphocytic Leukemia ◽  
Male Population ◽  
Hematological Disorders

Objectives: Bone marrow aspiration is a diagnostic test for various hematological disorders. Present study was designed to determine the percentages and frequency of benign and malignant hematological disorders diagnosed on bone marrow aspiration in Quetta. Study Design: Cross sectional study. Setting: Department of Hematology Sandeman Provincial Teaching Hospital Quetta and Bolan Medical Complex Quetta. Period: From Jan 2015 to Jan 2019. Material & Methods: The demographic variables were age and gender of the patients, while the research variables were benign hematological disorders and malignant hematological disorders. All the variables were presented in percentages and frequencies. Results: Out of total 478 hematological disorders 241(50.4%) were diagnosed with benign and 237(49.6%) were malignant hematological disorders. Majority of the patients were in the age range between 1-10 years. 62.3% was the male population whereas females comprised of only 37.7%. Megaloblastic Anemia having 14.2% was found to be the most common benign hematological disorders followed by Aplastic Anemia with 11.7% cases and Idiopathic Thrombocytopenic Purpura was present in 9.2%. Among the malignant disorders Acute Lymphocytic Leukemia 19%, Chronic Myeloid Leukemia 8.3% and Acute Myeloid Leukemia were found to be 5.8%. Conclusion: The most common benign hematological disorders were Megaloblastic anemia and Aplastic anemia whereas Acute Lymphocytic Leukemia and Chronic Myeloid Leukemia were the most remarkable malignant hematological disorder diagnosed on bone marrow aspiration in Quetta.

scholarly journals High-Sensitive TRBC1-Based Flow Cytometric Assessment of T-Cell Clonality in Tαβ-Large Granular Lymphocytic Leukemia

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 408
Author(s):  
Noemí Muñoz-García ◽  
F. Morán-Plata ◽  
Neus Villamor ◽  
Margarida Lima ◽  
Susana Barrena ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Effector Memory ◽  
Large Granular Lymphocytic Leukemia ◽  
Cell Counts ◽  
Flow Cytometric ◽  
Fcm Analysis ◽  
T Cell Clonality ◽  
Cell Clonality

Flow cytometric (FCM) analysis of the constant region 1 of the T-cell receptor β chain (TRBC1) expression for assessing Tαβ-cell clonality has been recently validated. However, its utility for the diagnosis of clonality of T-large granular lymphocytic leukemia (T-LGLL) needs to be confirmed, since more mature Tαβ cells (i.e., T-LGL normal-counterpart) show broader TRBC1+/TRBC1− ratios vs. total Tαβ cells. We compared the distribution and absolute counts of TRBC1+ and TRBC1− Tαβ-LGL in blood containing polyclonal (n = 25) vs. clonal (n = 29) LGL. Overall, polyclonal TRBC1+ or TRBC1− Tαβ-LGL ranged between 0.36 and 571 cells/μL (3.2–91% TRBC1+ cells), whereas the clonal LGL cases showed between 51 and 11,678 cells/μL (<0.9% or >96% TRBC1+ cells). Among the distinct TCRVβ families, the CD28− effector-memory and terminal-effector polyclonal Tαβ cells ranged between 0 and 25 TRBC1+ or TRBC1− cells/μL and between 0 and 100% TRBC1+ cells, while clonal LGL ranged between 32 and 5515 TRBC1+ or TRBC1− cells/μL, representing <1.6% or >98% TRBC1+ cells. Our data support the utility of the TRBC1-FCM assay for detecting T-cell clonality in expansions of Tαβ-LGL suspected of T-LGLL based on altered percentages of TRBC1+ Tαβ cells. However, in the absence of lymphocytosis or in the case of TαβCD4-LGL expansion, the detection of increased absolute cell counts by the TRBC1-FCM assay for more accurately defined subpopulations of Tαβ-LGL-expressing individual TCRVβ families, allows the detection of T-cell clonality, even in the absence of phenotypic aberrations.

MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 500-502 ◽  
Author(s):  
Francis J. Giles ◽  
Jorge Cortes ◽  
Dan Jones ◽  
Donald Bergstrom ◽  
Hagop Kantarjian ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Acute Lymphocytic Leukemia ◽  
Kinase Inhibitor ◽  
Philadelphia Chromosome ◽  
Aurora Kinase ◽  
Lymphocytic Leukemia ◽  
Clinical Activity ◽  
Clinical Responses

Abstract MK-0457 (VX-680) is a small-molecule aurora kinase (AK) inhibitor with preclinical antileukemia activity. The T315I BCR-ABL mutation mediates resistance to imatinib, nilotinib, and dasatinib. MK-0457 has in vitro activity against cells expressing wild-type or mutated BCR-ABL, including the T315I BCR-ABL mutation. Three patients with T315I abl-mutated chronic myeloid leukemia (CML) or Philadelphia chromosome (Ph)–positive acute lymphocytic leukemia (ALL) have achieved clinical responses to doses of MK-04547 that are not associated with adverse events. Higher MK-0457 dose levels were associated with clinical responses and down-regulation of CrkL phosphorylation in leukemia cells. The possible role of AK inhibition in these clinical responses requires further investigation. The currently reported cases are the first observed clinical activity of a kinase inhibitor against the T315I phenotype. The observation of responses in 3 patients with T315I phenotype–refractory CML or Ph-positive ALL, at doses of MK-0457 associated with no significant extramedullary toxicity, is very encouraging.

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