Somatic hypermutation profiles in stereotyped IGHV4-34 receptors from South American chronic lymphocytic leukemia patients

Stanganelli, Carmen; Torres, Davi Coe; Ortega, Claudia; Márquez, María Elena; Remedi, Victoria; Cabrera, Juana; Mardaraz, Claudia; Galvano, C; Krzywinski, Andrea; Lång, Cecilia; Zanella, Lorena; Agriello, Evangelina; Bezares, Raimundo F.; Pavlovsky, Astrid; Pavlovsky, Miguel Arturo; Oppezzo, Pablo; Slavutsky, Irma

doi:10.1007/s00277-021-04703-9

“…Globally, this group presented with a long TTFT compared with the rest of the patients, especially in the IGHV4-34 subfamily, the most common in our study and in other similar ones. 36 Interestingly, in patients with IGHV4 , we did not find poor prognosis FISH alterations (del11q and del17p), as previous reports 37 and conversely, del13q alone was observed in half of the patients. Our study further expands the evidence suggesting that this subset represents a group of patients with indolent disease.…”

Section: Discussionsupporting

confidence: 85%

Association of Cytogenetics Aberrations and IGHV Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting

Muñoz-Novas,

González-Gascón-y-Marín,

Figueroa

et al. 2024

Glob Med Genet

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Immunoglobulin heavy chain variable (IGHV) region mutations, TP53 mutation, fluorescence in situ hybridization (FISH), and cytogenetic analysis are the most important prognostic biomarkers used in chronic lymphocytic leukemia (CLL) patients in our daily practice. In real-life environment, there are scarce studies that analyze the correlation of these factors with outcome, mainly referred to time to first treatment (TTFT) and overall survival (OS). This study aimed to typify IGHV mutation status, family usage, FISH aberrations, and complex karyotype (CK) and to analyze the prognostic impact in TTFT and OS in retrospective study of 375 CLL patients from a Spanish cohort. We found unmutated CLL (U-CLL) was associated with more aggressive disease, shorter TTFT (48 vs. 133 months, p < 0.0001), and shorter OS (112 vs. 246 months, p < 0.0001) than the mutated CLL. IGHV3 was the most frequently used IGHV family (46%), followed by IGHV1 (30%) and IGHV4 (16%). IGHV5-51 and IGHV1-69 subfamilies were associated with poor prognosis, while IGHV4 and IGHV2 showed the best outcomes. The prevalence of CK was 15% and was significantly associated with U-CLL. In the multivariable analysis, IGHV2 gene usage and del13q were associated with longer TTFT, while VH1-02, +12, del11q, del17p, and U-CLL with shorter TTFT. Moreover, VH1-69 usage, del11q, del17p, and U-CLL were significantly associated with shorter OS. A comprehensive analysis of genetic prognostic factors provides a more precise information on the outcome of CLL patients. In addition to FISH cytogenetic aberrations, IGHV and TP53 mutations, IGHV gene families, and CK information could help clinicians in the decision-making process.

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“…The status of the IGHV genes is also associated with survival, such as patients with unmutated IGHV genes have a more aggressive disease course than patients with mutated IGHV genes [12]. A preferential IGHV gene utilization has been revealed in CLL, IGHV4-34 are the most predominant and usually display an indolent outcome [3]. The IGHV4-34 gene encodes germline autoreactive antibodies by recognizing N-acetyllactosamine contained in self and exogenous antigens, as the I/i blood group antigen.…”

Section: Discussionmentioning

confidence: 99%

“…There have been substantial advances in the field of CLL research in the last decade, including the identification of recurrent mutations, and clarification of clonal architectures, signalling molecules, and the multistep leukemogenic process, providing a comprehensive understanding of CLL pathogenesis [2]. IGHV4-34 is one of the most frequently used genes in CLL patients, which usually display an indolent outcome [3]. C/SP is a rare and benign plasma cell proliferative disease [4,5], but a few reports suggesting that it has the potential to transform into malignant tumours [6,7].…”

Section: Introductionmentioning

confidence: 99%

Treatment with Fenofibrate to a Patient with Newly Diagnosed Type 1 Diabetes, Rendering Him Insulin Independent

2024

Ann Case Report

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In our case, we encountered a patient with a very rare complication who was diagnosed with chronic lymphocytic leukemia (CLL) combined with cutaneous plasmacytosis(C/SP). Cutaneous plasmacytosis is a rare and benign plasma cell proliferative disease, but a few reports suggesting that it has the potential to transform into malignant tumours. However, to date, there have been no reported cases of cutaneous plasmacytosis combined with chronic lymphocytic leukemia. Single cell RNA-seq analysis and clonotype tracking revealed co-expression of IGHV4-34 by malignant B-lymphocytes and monoclonal plasma cells. Interestingly, the presence of IGHV4-34, which is one of the most frequently used genes in CLL patients, has rarely been reported in plasma cell diseases. This indicated that there might be a similarity or homology between the malignant B-lymphocytes and monoclonal plasma cells in this particular patient.

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“…The status of the IGHV genes is also associated with survival, such as patients with unmutated IGHV genes have a more aggressive disease course than patients with mutated IGHV genes [12]. A preferential IGHV gene utilization has been revealed in CLL, IGHV4-34 are the most predominant and usually display an indolent outcome [3]. The IGHV4-34 gene encodes germline autoreactive antibodies by recognizing N-acetyllactosamine contained in self and exogenous antigens, as the I/i blood group antigen.…”

Section: Discussionmentioning

confidence: 99%

“…There have been substantial advances in the field of CLL research in the last decade, including the identification of recurrent mutations, and clarification of clonal architectures, signalling molecules, and the multistep leukemogenic process, providing a comprehensive understanding of CLL pathogenesis [2]. IGHV4-34 is one of the most frequently used genes in CLL patients, which usually display an indolent outcome [3]. C/SP is a rare and benign plasma cell proliferative disease [4,5], but a few reports suggesting that it has the potential to transform into malignant tumours [6,7].…”

Section: Introductionmentioning

confidence: 99%

Cutaneous Plasmacytosis Complicated with Chronic Lymphocytic Leukemia: A Case Report

2024

Ann Case Report

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In our case, we encountered a patient with a very rare complication who was diagnosed with chronic lymphocytic leukemia (CLL) combined with cutaneous plasmacytosis(C/SP). Cutaneous plasmacytosis is a rare and benign plasma cell proliferative disease, but a few reports suggesting that it has the potential to transform into malignant tumours. However, to date, there have been no reported cases of cutaneous plasmacytosis combined with chronic lymphocytic leukemia. Single cell RNA-seq analysis and clonotype tracking revealed co-expression of IGHV4-34 by malignant B-lymphocytes and monoclonal plasma cells. Interestingly, the presence of IGHV4-34, which is one of the most frequently used genes in CLL patients, has rarely been reported in plasma cell diseases. This indicated that there might be a similarity or homology between the malignant B-lymphocytes and monoclonal plasma cells in this particular patient.

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Somatic hypermutation profiles in stereotyped IGHV4-34 receptors from South American chronic lymphocytic leukemia patients

Cited by 4 publications

References 36 publications

Association of Cytogenetics Aberrations and IGHV Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting

Association of Cytogenetics Aberrations and IGHV Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting

Treatment with Fenofibrate to a Patient with Newly Diagnosed Type 1 Diabetes, Rendering Him Insulin Independent

Cutaneous Plasmacytosis Complicated with Chronic Lymphocytic Leukemia: A Case Report

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