Fiche publication


Date publication

février 2015

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BOUVIER Anne-Marie , Dr GUERIN Eric


Tous les auteurs :
Rizzo D, Chauzeix J, Trimoreau F, Woillard JB, Genevieve F, Bouvier A, Labrousse J, Poli C, Guerin E, Dmytruk N, Remenieras L, Feuillard J, Gachard N

Résumé

We examined the significance of IgM peaks in chronic lymphocytic leukemia (CLL), including its association with newly reported MYD88, BIRC3, NOTCH1 and SF3B1 mutations. A total of 27, 25, 41 and 57 patients with monoclonal IgM or IgG peaks (IgM and IgG groups), hypogammaglobulinemia (Hypo-gamma group) and normal immunoglobulin serum levels (normal-gamma group) were, respectively, included. IgM peaks were mainly associated with Binet stage C and the del(17p). Biased usage of IGHV3-48 was shared by both IgM and IgG groups. IGHV3-74 and IGHV4-39 gene rearrangements were specific for IgM and IgG peaks, respectively. SF3B1, NOTCH1, MYD88 and BIRC3 mutation frequencies were 12%, 4%, 2% and 2%, respectively, being over-represented in IgM, IgG and Hypo-gamma groups for SF3B1, and being equal between normal-gamma and IgM groups for MYD88. Overall, 76%, 87%, 49% and 42% of cases from IgM, IgG, Hypo-gamma and normal-gamma groups had at least one intermediate or poor prognosis genetic marker, respectively. By multivariate analysis, IgM peaks were associated with shorter treatment-free survival independently from any other univariate poor prognosis biological parameters, including IgG peaks, Hypo-gamma, IGHV status, SF3B1 mutations, cytogenetics and lymphocytosis. Therefore, as with IgG peaks, IgM peaks aggravated the natural course of CLL, with increased accumulation of adverse genetic events.

Référence

Leukemia. 2015 Feb;29(2):337-45