The most frequent t(14;19)(q32;q13)-positive B-cell malignancy corresponds to an aggressive subgroup of atypical chronic lymphocytic leukemia

Chapiro, Élise; Radford‐Weiss, Isabelle; Bastard, Christian; Luquet, Isabelle; Lefebvre, Catherine Lemieux; Callet‐Bauchu, Evelyne; Leroux, Dominique; Talmant, Pascaline; Mj, Mozziconacci; Mugneret, Francine; Struski, Stéphanie; Raynaud, Sophie; Andrieux, Joris; Barin, Carole; Jotterand, Martine; Mossafa, Hossein; Ramond, Sylvie; Terré, Christine; Lippert, Éric; Berger, Françoise; Felman, Pascale; Merle-Béral, Hélène; Bernard, Olivier A.; Davi, Frédéric; Berger, Roland; Nguyen‐Khac, Florence

doi:10.1038/leu.2008.102

Cited by 47 publications

(48 citation statements)

References 8 publications

(8 reference statements)

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“…Loss of TP53 gene is frequently due to rearrangements involved in chromosome region 17p10, 17p12 (Fink et al, 2006;Mayr et al, 2006). Some translocations affecting this region have been described t(17;21)(p11;q11), dic(15;17)(p11;p11), dic(17;18)(p11;p11), dic(4;17)(p11;p11) ( Döhner et al, 1995;Callet-Bauchu et al, 1996;Chapiro et al, 2008;Woyach et al, 2010). In addition, patients with translocations have been reported to have higher CD38 expression, advanced disease and significantly inferior overall survival than those without translocations (Mayr et al, 2006;Cavazzini et al, 2008).…”

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confidence: 99%

A new genetic abnormality leading to TP53 gene deletion in chronic lymphocytic leukaemia

López¹,

Baumann²,

Costa³

et al. 2011

Br J Haematol

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SummaryThe analysis of chromosomal abnormalities provides significant prognostic information in patients with chronic lymphocytic leukaemia (CLL), a disease with a highly heterogeneous clinical course. Chromosomal abnormalities commonly found are trisomy 12, del(13)(q14), del(11)(q22‐23), del(17)(p13) and del(6)(q21). Translocations are present in some patients and affect regions recurrently involved in CLL. This report describes the clinical and pathological characteristics of four CLL patients showing a new recurrent chromosomal abnormality dic(8;17)(p11;p11), that implied loss of the TP53 gene in all cases. In addition, TP53 gene was mutated in three out of four patients. Mechanically, Low Copy Repeats (LCR) in 17p12 and 8p11 may explain the origin of the translocation by non‐allelic homologous recombination (NAHR). Isolated dic(8;17)(p11;p11) in patients with mutated IGHV genes status may not have the same prognostic impact as other mutations or deletions affecting the TP53 gene. Larger series are needed to better evaluate the clinical impact of this chromosomal aberration during the course of the disease.

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confidence: 99%

A new genetic abnormality leading to TP53 gene deletion in chronic lymphocytic leukaemia

López¹,

Baumann²,

Costa³

et al. 2011

Br J Haematol

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“…6 Notably, this subset was subsequently shown to be associated with the chromosomal translocation t(14;19)(q32;q13) coexisting with trisomy 12. 7,8 In such cases, the BCL-3 protooncogene at 19q13 is juxtaposed to the immunoglobulin heavy chain gene locus at 14q32, leading to overexpression of the Table 2 CD38 expression and IGHV gene mutational status in cases assigned to the +12,+19 subgroup ('+12+19') to cases exhibiting trisomy 12 yet without coexisting trisomy 19 ('+12 non +19') and cases negative for trisomy 12 ('no +12') BCL-3 protein with resultant deregulation of the nuclear factor-kB pathway. Although the þ 12, þ 19 profile described here identifies a CLL subgroup distinct from subset 8, especially in terms of the IGHV repertoire and mutational status, the fact that aberrations of chromosome 19 are biased to sIgG-switched CLL might be considered as evidence of genetic evolution along distinctive yet related, likely antigen-driven and B-cell receptormediated, pathways.…”

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Coexistence of trisomies of chromosomes 12 and 19 in chronic lymphocytic leukemia occurs exclusively in the rare IgG-positive variant

et al. 2011

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“…26,31,32, 81 Therefore, it is plausible that an unlimited capacity to respond to an extensive range of microenvironmental stimuli, through the surface BCR Ig and the TLRs, may elicit unabated stimulation throughout the natural history of subset #8 patients resulting in enhanced survival and expansion of the malignant clone. How this relates to the distinctive genetic profile or conversely may facilitate the accumulation of genetic aberrations in subset #8 remains to be elucidated.…”

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confidence: 99%

Excessive antigen reactivity may underlie the clinical aggressiveness of chronic lymphocytic leukemia stereotyped subset #8

Gounari

Ntoufa

Apollonio

et al. 2015

Blood

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Key Points• mAbs from aggressive CLL subset #8 display extreme antigen polyreactivity, in clear contrast with the mAbs from other aggressive CLL subsets.• Subset #8 CLL clones respond avidly to stimulation by multiple antigens and this may underlie their noted propensity to transform.Subset #8 is a distinctive subset of patients with chronic lymphocytic leukemia (CLL) defined by the expression of stereotyped IGHV4-39/IGKV1(D)-39 B-cell receptors. Subset #8 patients experience aggressive disease and exhibit the highest risk for Richter transformation among all CLL. In order to obtain biological insight into this behavior, we profiled the antigen reactivity and signaling capacity of subset #8 vs other clinically aggressive stereotyped subsets, namely subsets #1 and #2. Twenty-seven monoclonal antibodies (mAbs) from subsets #1, #2, and #8 CLL clones were prepared as recombinant human immunoglobulin G1 and used as primary antibodies in enzyme-linked immunosorbent assays against representatives of the major classes of established antigenic targets for CLL. Subset #8 CLL mAbs exhibited broad polyreactivity as they bound to all antigens tested, in clear contrast with the mAbs from the other subsets. Antigen challenge of primary CLL cells indicated that the promiscuous antigen-binding activity of subset #8 mAbs could lead to significant cell activation, again in contrast to the less responsive CLL cells from subsets #1 and #2. These features constitute a distinctive profile for CLL subset #8, supporting the existence of distinct mechanisms of aggressiveness in different immunogenetic subsets of CLL. (Blood. 2015;125(23):3580-3587)

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The most frequent t(14;19)(q32;q13)-positive B-cell malignancy corresponds to an aggressive subgroup of atypical chronic lymphocytic leukemia

Cited by 47 publications

References 8 publications

A new genetic abnormality leading to TP53 gene deletion in chronic lymphocytic leukaemia

A new genetic abnormality leading to TP53 gene deletion in chronic lymphocytic leukaemia

Coexistence of trisomies of chromosomes 12 and 19 in chronic lymphocytic leukemia occurs exclusively in the rare IgG-positive variant

Excessive antigen reactivity may underlie the clinical aggressiveness of chronic lymphocytic leukemia stereotyped subset #8

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