Logo image
Retour
Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes
Article de revue scientifique   Avec comité de lecture

Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes

Aliki Xochelli, Panagiotis Baliakas, Ioannis Kavakiotis, Andreas Agathangelidis, Lesley-Ann Sutton, Eva Minga, Stavroula Ntoufa, Eugen Tausch, Xiao-Jie Yan, Tait Shanafelt, …
Clinical cancer research, Vol.23(17), p.5292-5301
01/09/2017
DOI: https://doi.org/10.1158/1078-0432.CCR-16-3100
PMID: 28536306

Résumé

ADP-ribosyl Cyclase 1 - genetics ADP-ribosyl Cyclase 1 - immunology Amino Acid Sequence - genetics Female Gene Expression Regulation, Neoplastic - immunology Humans Immunogenetics Immunoglobulin Heavy Chains - genetics Immunoglobulin Heavy Chains - immunology Immunoglobulin Variable Region - genetics Immunoglobulin Variable Region - immunology Leukemia, Lymphocytic, Chronic, B-Cell - genetics Leukemia, Lymphocytic, Chronic, B-Cell - immunology Leukemia, Lymphocytic, Chronic, B-Cell - pathology Male Somatic Hypermutation, Immunoglobulin - genetics
We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34-expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly ( < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management. .

Indicateurs

1 Consultations de la notice

Détails

Logo image