Recurrent 14q32 translocations determine the prognosis of multiple myeloma, especially in patients receiving intensive chemotherapy

Abstract

Recently, we have described the biological correlations associated with the main translocations involving the 14q32 chromosomal region, that is, t(14q32), in patients with multiple myeloma (MM). We have now extended the analysis to the prognostic value of these chromosomal rearrangements in 168 consecutive patients with newly diagnosed MM receiving intensive chemotherapy within clinical trials of the Intergroupe Francophone du Myelome (IFM). Patients with t(4;14) displayed a poor outcome (short event-free survival and short overall survival), whereas those with t(11;14) displayed long survival. On the other hand, patients with neither t(4;14) nor t(11;14) presented an intermediate outcome. Importantly, chromosome 13 abnormalities (C13As) significantly influence the prognosis of this latter group. In contrast, C13As affected the outcome of the other patients to a much lesser extent, either because of an almost constant association (in the t(4;14) group) or because of a lack of any significant prognostic impact (in the t(11;14) group; only one event occurred in the 10 patients with t(11;14) and C13As). Considering that t(4;14) and t(11;14) (1) are the only (so far recognized) true, recurrent t(14q32)'s, (2) are linked to specific immunoglobulin isotypes, and (3) display specific outcomes, they represent distinct entities corresponding to a specific oncogenesis and prognosis. These data emphasized the interest in analyzing these two translocations by fluorescence in situ hybridization in prospective therapeutic trials in order to consider these translocations as distinct entities.