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Translocation t(14;16)(q32;q23) in plasma cells is considered as a strong negative prognostic factor in patients with multiple myeloma (MM). The oncogenic potential of this chromosomal aberration is based on the overexpression of the c-MAF protooncogene (located at 16q23) under strong enhancer of IgH gene (14q32). Although the IgH/MAF positive cases comprise just 2-4% of MM patients, the evaluation of this aberration is an integral part of the cytogenetic risk stratification according the RISS. The International Myeloma Working Group (IMWG) proposed a model of high risk MM as having at least one of the following aberrations: deletion of 17p13 (TP53 gene), translocation t(4;14)(p13;q32) and translocation t(14;16)(q32;q23) determined by FISH. However, the unequivocal poor prognostic value of t(14;16)(q32;q23) was not confirmed in several MM series thus further studies are needed.

The aim of our study was to assess the impact of t(14;16)(q32;q23) on event free (EFS) and overall survival (OS) in cohort of IgH/MAF positive MM patients in comparison with control group of 30 MM IgH/MAF negative cases.

During the years 2004 to 2016, we examined 870 bone marrow samples of MM patients on immunofluorescently labeled plasma cells (cIg FISH). The basic FISH panel included 4 specific DNA probes (Abbott-Vysis, Kreatech and MetaSystems) detecting: the IgH gene rearrangement (1), deletion 13q14 (RB1 gene)/monosomy 13 (2), gain of 1q21/deletion of 1p32 (3) and deletion of TP53 gene (4). Cases with rearranged IgH gene were gradually examined for 3 specific translocations- 1) t(11;14)(q13;q32), 2) t(4;14)(p16;q32) and 3) t(14;16)(q32;q23). Kaplan-Maier analysis was performed to evaluate OS and EFS.

Translocation t(14;16) was identified in 19 out of 870 patients (2.2%). Eighteen patients were examined at the time of diagnosis and one at the time of the progression of asymptomatic myeloma to symptomatic disease. Relapse and/or disease progression occurred in 15 patients. The median event-free survival (EFS) was 13 months in t(14;16) carriers (range 3 – 62 months) and 22.5 months in controls (range 3-71 months, p=0.285). Fourteen t(14;16) positive patients died. The median overall survival (OS) was 25 months (range 10-204 months) in comparison with 52 months in control group (range 3-132 months). However, the difference in OS was not statistically significant (p=0.155). In 15 t(14;16) positive patients (83.3%), two or more additional chromosomal changes were detected by FISH (monosomy/deletion of chromosome 13 being the most frequent). In four cases, (14;16) was detected together with another high risk chromosomal change - deletion of TP53 gene - and all these patients died within median of OS 12.5 months (range 10-16).

Beside its supposed negative clinical impact, the examination of t(14;16) is not always included in routine diagnostics of chromosomal changes and its prognostic significance should be proved in large series of MM patients. Our data substantiate the trend of worse clinical outcome (shorter OS) in t(14;16) positive group compared to IgH/MAF negative MM controls. The detailed analysis of other clinical parameters, type of therapy, combination with other chromosomal aberrations will be performed to prove its role of as independent prognostic factor.

Supported by grants RVO-VFN64165, ProgresQ28 and GACR P302/12/G157.