First Case of Double T-Cell Receptor Alpha/Delta Rearrangements of t(11;14) and inv(14) and Subsequent JAK2 Rearrangement in a Patient With T-cell Acute Lymphoblastic Leukemia

Abstract B-cell acute lymphoblastic leukemia (B-ALL) results from clonal expansion of B-lymphocytes derived at different stage of differentiation. Immunoglobulin (Ig) heavy chain genes (IGH), light chain kappa (IGK) and lambda (IGL) genes rearrange during early B-lymphocyte differentiation. T-cell receptor (TCR) genes are considered to rearrange exclusively in normal T lymphocytes, but malignant B lymphoblasts often contain crosslineage rearranged TCR genes. The clonal leukemic cell population, carrying identical copies of rearranged Ig and/or TCR genes, can be identified above 95% of B-ALL patients. In our study Ig/TCR genes rearrangements were detected by multiplex PCR with heteroduplex analysis according to BIOMED-2 protocol. DNA was isolated by column method from mononuclear cells isolated from the peripheral blood/bone marrow samples obtained at initial diagnosis from 36 B-ALL patients. Monoclonal rearrangements of Ig genes were detected in 100% (36/36) of patients. The most frequent rearrangements were observed in IGH genes (94%), including complete IGHV-IGHJ in 83% (30/36) and incomplete IGHD-IGHJ in 22% (8/36) of patients. Among complete IGH rearrangements 2 biallelic rearrangements in IGHV1-7 and IGHJ genes (FR3) were found. Ig light chain genes rearrangements were identified in 26 patients (72%) (including 64% of IGKV-IGKJ, 47% IGKV/intron-Kde, and 22% IGLV-IGLJ) what indicates active receptor editing occurring during B lymphoblasts leukemogenesis. Crosslineage TCR genes rearrangements were found in 97% (35/36) of patients. TCR beta genes rearrangements were detected in 47% (17/36) of patients (complete TRBV-TRBJ in 25% (9/36), TRBD-TRBJ in 6/36 patients - 17%). TRGV-TRGV in 58% (21/36), TRDV-TRDJ in 58% (21/36); 17 monoallelic and 4 biallelic were found. The inactivation of potentially functional IGKV-IGKJ by secondary rearrangements indicates active receptor editing. Our data describe IGK and IGL genes rearrangements incidence, present allelic exclusion and active receptor editing in B-ALL patients. B-ALL lymphoblast undergoes rearrangement on the same IGK allele before IGL genes rearrangement occur. The data may suggest the possible of antigens in B-ALL immunopathogenesis. The results indicate also rearranged IGK, IGL and TCR genes as stable molecular marker for monitoring MRD in B-ALL.

Download Full-text

T-cell Receptor γ and δ Gene Rearrangements in T-cell Acute Lymphoblastic Leukemia in Indian Patients

Leukemia & Lymphoma ◽

10.3109/10428190009148854 ◽

2000 ◽

Vol 36 (3-4) ◽

pp. 331-338 ◽

Cited By ~ 8

Author(s):

Jyoti Kode ◽

Suresh Advani ◽

Shubhada Chiplunkar

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

T Cell Receptor ◽

Lymphoblastic Leukemia ◽

Cell Receptor ◽

Gene Rearrangements ◽

Indian Patients ◽

Cell Acute Lymphoblastic Leukemia

Download Full-text

Comparative gene expression profiling of T-cell acute lymphoblastic leukemias (T-ALL) expressing the T-cell receptor 𝛂β or γδ (T-ALL𝛂β / T-ALLγδ)

10.31219/osf.io/cyhnq ◽

2019 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Gene Expression ◽

Acute Lymphoblastic Leukemia ◽

T Cell ◽

T Cell Receptor ◽

Expression Profiling ◽

Lymphoblastic Leukemia ◽

Cell Receptor ◽

Differentially Expressed ◽

Aggressive Form ◽

Cell Acute Lymphoblastic Leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive form of leukemia with inferior treatment outcomes. The T-cell receptor (TCR) exists in two major forms: the 𝛂βTCR or the γδTCR, and 20-35% of T-ALL cases express either the 𝛂βTCR or the γδTCR (T-ALL𝛂β or T-ALLγδ). Using a published dataset from a cohort of 14 TCR+ T-ALL patients, I found a series of genes that are differentially expressed among patients T-ALL𝛂β or T-ALLγδ. Any number of these differentially expressed genes may be a scientifically and/or clinically actionable target in TCR+ T-ALL.

Download Full-text

T Cell Receptor Gamma and Delta Gene Rearrangements in T-cell Acute Lymphoblastic Leukemia in South India and Quantitation of Minimal Residual Disease

Nature Precedings ◽

10.1038/npre.2010.5274.1 ◽

2010 ◽

Cited By ~ 1

Author(s):

Sudhakar Natarajan ◽

Nirmala Nancy ◽

Rajalekshmy Kamalalayam ◽

Rajkumar Thangarajan

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

T Cell Receptor ◽

South India ◽

Residual Disease ◽

Lymphoblastic Leukemia ◽

Cell Receptor ◽

Gene Rearrangements ◽

Cell Acute Lymphoblastic Leukemia ◽

Minimal Residual

Download Full-text

Crosslineage T-Cell Receptor Genes Rearrangements and Active Receptor Editing in B-Cell Acute Lymphoblastic Leukemia.

Blood ◽

10.1182/blood.v108.11.4480.4480 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4480-4480

Author(s):

Hanna Makuch-Lasica ◽

Miroslaw Majewski ◽

Grazyna Nowak ◽

Monika Lewandowska ◽

Iwona Solarska ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

B Cell ◽

T Cell Receptor ◽

Light Chain ◽

Lymphoblastic Leukemia ◽

Cell Receptor ◽

Heteroduplex Analysis ◽

Receptor Editing ◽

Cell Acute Lymphoblastic Leukemia

Abstract B-cell acute lymphoblastic leukemia (B-ALL) results from clonal expansion of B-lymphocytes derived at different stage of differentiation. Immunoglobulin (Ig) heavy chain genes (IGH), light chain kappa (IGK) and lambda (IGL) genes rearrange during early B-lymphocyte differentiation. T-cell receptor (TCR) genes are postulated to rearrange exclusively in normal T lymphocytes, but malignant B lymphoblasts often contain crosslineage rearranged TCR genes. The clonal leukemic cell population, carrying identical copies of rearranged Ig and/or TCR genes, can be identified above 95% of B-ALL patients. In our study Ig/TCR genes rearrangements were detected by multiplex PCR with heteroduplex analysis according to BIOMED-2 protocol. DNA was isolated by column method from mononuclear cells isolated from the peripheral blood/bone marrow samples obtained at initial diagnosis from 28 B-ALL patients. Monoclonal rearrangements of Ig genes were detected in 96% (27/28) of patients. The most frequent rearrangements were observed in IGH genes (96%), including complete IGHV-IGHJ in 75% (21/28) and incomplete IGHD-IGHJ in 31% (8/28) of patients. Among complete IGH rearrangements 4 biallelic rearrangements in IGHV1-7 and IGHJ genes (FR3) were found. Ig light chain genes rearrangements were identified in 20 patients (71%) (including 25% of IGKV-IGKJ, 50% of IGKV/intron-Kde, and 25% of IGLV-IGLJ) indicating active receptor editing occurring during B lymphoblasts leukemogenesis. Cross-lineage TCR genes rearrangements were found in 77% (23/28) of patients. TCR beta genes rearrangements were detected in 46% (13/28) of patients (complete TRBV-TRBJ in 32% (9/28), TRBD-TRBJ in 5/28 patients - 18%). TRGV-TRGV were found in 46% (13/28), TRDV-TRDJ in 50% (14/28; 10 monoallelic and 4 biallelic). TCR beta genes rearrangements with presence of TCR gamma genes rearrangements were identified in 25% (7/28) of patients. The identified Ig and TCR rearrangements were stable in patients monitored for minimal residual disease (MRD) and patients with leukemia relapse. The inactivation of potentially functional IGKV-IGKJ by secondary rearrangements indicates active receptor editing. Our data describe IGK and IGL genes rearrangements incidence, present allelic exclusion and active receptor editing in B-ALL patients. B-ALL lymphoblasts undergo many rearrangements on the same IGK allele before they rearrange IGL genes. The data suggest the role of antigen in B-ALL immunopathogenesis. The results indicate also rearranged IGK, IGL and TCR genes as a possible molecular marker for monitoring MRD in B-ALL.

Download Full-text