Finding of clonal chromosomal aberrations in plasma cells is considered as one of the most important and independent prognostic factor in patients with multiple myeloma (MM). The most frequent and reliable cytogenetic indicators are chromosome 13q deletions (intermediate or moderately adverse prognosis), and translocations involving the immunoglobulin heavy chain gene (IgH) at 14q32 region. IgH gene is involved in translocations with different partner genes and these rearrangements are related to a very poor prognosis. The only exception is translocation t(11;14)(q13;q32) which is often connected with longer overall survival and therefore considered to be a favorable prognostic factor. The aim of the study was to assess the frequency of the most important chromosomal aberrations in immunofluorescently labeled plasma cells of patients with MM by interphase fluorescence in situ hybridization (I-FISH), and to evaluate their prognostic significance.

During the last two years we examined 128 newly diagnosed patients with MM by conventional G-banding technique and by I-FISH. We focused on detection of aberrations of 13q, IgH gene rearrangements, and t(11;14)(q13;q32) translocation. I-FISH was done by locus-specific DNA probes (Abbott-Vysis, Des Plaines, Illinois, USA). Fifteen patients with complex karyotype were re-examined by multicolor FISH (mFISH, MetaSystems GmbH, Altlussheim, Germany). G-banding revealed abnormal karyotypes in 25% of patients, I-FISH detected chromosomal abberations in 82.8% cases. Abberations of chromosome 13 were found in plasma cells of 84 patients (65,6%), the incidence was: del(13)(q14) in 11%, monosomy 13 in 40%, combination of del(13)(q14)/monosomy 13 in 8%, and other aberrations of chromosome 13 in 7% of cases. Aberrations of IgH gene were proved in 82 patients (64%). t(11;14)(q13;q32) was seen in fourteen patients (11%) and other translocations affecting 14q32 region in 19 patients (15%). Besides translocations, different variations of total and/or partial deletions of IgH gene were detected in 28 cases (22%). In nine patients (7%) we found clones with translocation and deletion of 14q32 simultaneously, twelve patients (9%) had other IgH aberrations. Univariate statistical testing showed aberrations of 13q (p=0.042), and IgH gene rearrangments (translocations except t(11;14)(q13;q32) or deletions; p=0.007) to be associated with significantly shorter progression-free survival. The worst prognosis in our cohort was for 18 patients with combination of chromosome 13 anomalies together with rearrangements of IgH gene (p=0.049). Method of immunofluorescent labeling of plasma cells allows higher detection of chromosomal changes by I-FISH technique and therefore correct prognosis of the disease can be done.

Grant support: MZO 00064165, IGA NR/8183-4 and MSM 0021620808.

Disclosure: No relevant conflicts of interest to declare.

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