Immunoglobulin heavy chain V-D-J gene rearrangement and mutational status in Uruguayan patients with chronic lymphocytic leukemia

Bianchi, Sergio; Moreno, Pilar; Landoni, Ana Inés; Naya, Hugo; Oppezzo, Pablo; Dighiero, G; Gabús, Raúl; Pritsch, Otto

doi:10.3109/10428194.2010.522283

Cited by 8 publications

(4 citation statements)

References 44 publications

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“…Based on the stringent criteria for the analysis of stereotype in IGHV CDR3 amino acid sequences (Darzentas et al , ), the expression frequency of stereotyped BCR was lower than those observed in Western studies (Stamatopoulos et al , ; Agathangelidis et al , ; Marinelli et al , ) (18·3% vs. 25–30%). The length of IGHV CDR3 in the mutated CLL patients was significantly smaller than that in the un‐mutated CLL cases in the present study, as well as in other Asian or Western countries (Bianchi et al , ; Agathangelidis et al , ; Marinelli et al , ; Rani et al , ), suggesting that mutated IGHV and smaller CDR3 length might work together to affect the antibody‐binding pocket for antigen. According to the studies listed in Table SI, there was a reverse correlation of the frequency of patients with stereotyped BCR and mutated IGHV .…”

Section: Discussionsupporting

confidence: 48%

Distinct immunoglobulin heavy chain variable region gene repertoire and lower frequency of del(11q) in Taiwanese patients with chronic lymphocytic leukaemia

et al. 2019

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Summary Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in Western countries but very rare in Asia. Peripheral blood or bone marrow mononuclear cells obtained at initial diagnosis from 194 patients with CLL were analysed to determine the ethnic difference in genetic abnormalities. Mutated IGHV was detected in 71·2% of Taiwanese CLL and IGHV3‐23 was the most frequently used gene. Stereotyped BCR was present in 18·3% with subset 8 being the most frequent. All cases with subset 8 belonged to IGHV 4‐39 and were exclusively associated with un‐mutated IGHV and poor outcome. Mutation frequencies of SF3B1 (9·7%), NOTCH1 (8·6%), BIRC3 (1·1%), ATM (16·9%) or TP53 (8·1%), and frequencies of cytogenetic abnormalities including trisomy 12 (18·6%), del(17p) (10·4%), del(13q) (43·7%) and IGH translocation (10·1%) were comparable to those reported from Western countries, except del(11q) (6·9%) which was lower in our patients. Patients with un‐mutated IGHV, subset 8, disrupted TP53, trisomy 12, and SF3B1 mutations had a worse outcome compared to patients without these mutations. In conclusion, IGHV3‐23 usage, stereotyped subset 8 and lower frequency of del(11q) show an ethnicity‐dependent association in Taiwanese CLL patients.

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Section: Discussionsupporting

confidence: 48%

Distinct immunoglobulin heavy chain variable region gene repertoire and lower frequency of del(11q) in Taiwanese patients with chronic lymphocytic leukaemia

et al. 2019

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“…31 In recent years, several groups have reported differences in IgVH gene usage in CLL among different geographic areas (Europe, USA, China, Japan and Iran). 32 Also, somatic mutations are not uniformly distributed within IgVH gene families, as they predominate among IgVH3 and IgVH4 families, whereas an UM profile is prevalent in the IgVH1 family. The most frequently used IgVH genes in CLL rearrangements in Western countries are IGHV1–69, IGHV3–07, IgVH 3–21 and IgVH 4–34 .…”

Section: The Bcr In Cllmentioning

confidence: 99%

“…The most frequently used IgVH genes in CLL rearrangements in Western countries are IGHV1–69, IGHV3–07, IgVH 3–21 and IgVH 4–34 . 32 However, the available data from Japan, China and Iran show some differences with those from Western countries. The frequency of VH1–69 in Japan and Iran is lower than that in Western countries.…”

Section: The Bcr In Cllmentioning

confidence: 99%

“Role of the B-cell receptor and the microenvironment in chronic lymphocytic leukemia’’

Oppezzo

Dighiero

2013

Blood Cancer Journal

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Despite significant progress in treatment, chronic lymphocytic leukemia (CLL) remains an incurable disease. Advances have been made to understand the molecular pathogenesis underlying CLL progression and treatment resistance. We here review the available evidences concerning the role of the B-cell receptor (BCR) and the tumor microenvironment interactions in CLL pathogenesis. Antigen likely has a key role in the selection of the tumoral clone, the mutational status of immunoglobulin genes is a strong prognostic predictor and BCR signaling has been postulated to have a role for CLL trafficking and interaction with the stromal microenvironment. There is also important evidence, favoring a role for the microenvironment in CLL pathogenesis. Most, if not all, proliferative events occur in the lymph nodes and bone marrow, where leukemic cells receive through microenvironment interactions survival signals aiming to avoid apoptosis and acquire favorable tumoral growing conditions. In addition, the tumoral microenvironment appears to be the site where the acquisition of additional genetic lesions in the clone occur, which should greatly influence clinical outcome. The advent of new tyrosine kinase inhibitors which seem to be able to modulate microenvironment interactions and circumvent the p53 deletion have generated significant promise by raising the possibility that they could provide significant progress in disease treatment.

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“…been reported [79,82,[85][86][87][88][89]. For example, IGHV3-21 gene has been detected in IGHV-IGHD-IGHJ rearrangements of more than 11% of Scandinavian patients, while it was less frequent intheUK(7.9%)andveryrareinMediterraneancohorts(lessthan3%ofcases) [79,[90][91][92][93].…”

Section: Geographicalandethnicaldifferencesinighvgeneusageincllrearramentioning

confidence: 99%

Somatic Hypermutational Status and Gene Repertoire of Immunoglobulin Rearrangements in Chronic Lymphocytic Leukemia

Karan-Djurašević¹,

Pavlović²

2017

Lymphocyte Updates - Cancer, Autoimmunity and Infection

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Immunoglobulin molecule is the key component of B cell receptor (BCR), which governsthesurvival,differentiationandfunctionofnormalBlymphocytes,butaccumulating data suggest that, in the case of chronic lymphocytic leukaemia (CLL), it is also involved in the pathogenesis and clinical course of the disease. CLL is a malignancy of mature CD5 + CD19 + CD23 + sIgM low B lymphocytes and is characterized by extremely heterogeneous clinical course, which varies from indolent to rapidly progressive. Somatic hypermutational status of immunoglobulin heavy chain variable genes(IGHV)definestwoCLLsubtypes,mutated(M-CLL)andunmutated(U-CLL). U-CLL patients suffer from more aggressive disease, characterized by shorter time to treatment, progression-free survival and overall survival in comparison to M-CLL patients. Since these correlations are not dependent on the clinical stage and since there is no interconversion between subtypes, IGHV mutational status is currently the most reliable prognostic marker in CLL. Several lines of evidence indicate that both M-CLLandU-CLLarisefromanantigen-experiencedcelloforigin.Immunogenetic studies have revealed CLL-biased usage of immunoglobulin variable region genes, as well as the existence of highly homologous, 'stereotyped' BCRs in CLL clones, strongly implying the role of antigenic drive in the development and evolution of the disease.

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Immunoglobulin heavy chain V-D-J gene rearrangement and mutational status in Uruguayan patients with chronic lymphocytic leukemia

Cited by 8 publications

References 44 publications

Distinct immunoglobulin heavy chain variable region gene repertoire and lower frequency of del(11q) in Taiwanese patients with chronic lymphocytic leukaemia

Distinct immunoglobulin heavy chain variable region gene repertoire and lower frequency of del(11q) in Taiwanese patients with chronic lymphocytic leukaemia

“Role of the B-cell receptor and the microenvironment in chronic lymphocytic leukemia’’

Somatic Hypermutational Status and Gene Repertoire of Immunoglobulin Rearrangements in Chronic Lymphocytic Leukemia

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