CHRONIC LYMPHOCYTIC LEUKEMIA WITH MUTATED IGHV4-34 RECEPTORS: SHARED AND DISTINCT IMMUNOGENETIC FEATURES AND CLINICAL OUTCOMES

We sought to investigate if B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features amongst 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. Experimental Design: 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. Results:We identified shared and subset-specific patterns of somatic hypermutation (SHM) amongst 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 CLLs. 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 (p