c-MAF protein expression in multiple myeloma

Background . The c-MAF oncogene, located in the 16q23.2 region, encodes the protein of the same name, a transcription factor whose role continues to be studied. Given the activating effect of the c-MAF transcription factor in enhancing the interaction between the tumor cell and the bone marrow stroma, we hypothesized that c-MAF protein expression would be more frequently detected in multiple myeloma (MM) patients without plasmacytomas.Aim. To analyze the c-MAF protein expression pattern in bone marrow trephine biopsy specimens of patients with newly diagnosed MM with and without plasmacytomas. Materials and methods . The retrospective single-center study included 31 patients (7 men and 24 women) with newly diagnosed MM aged 29 to 78 years (median – 55 years). The first cohort of patients included 12 patients with t(14;16), the second cohort – 19 patients without this translocation. In 21 patients, plasmacytomas were not detected at the disease onset, in 10 patients, bone or extramedullary plasmacytomas were detected. Low-dose body computed tomography was used to detect bone lesions. The diagnosis was established in accordance with the International Myeloma Working Group 2014 criteria. Positive immunomagnetic selection of CD138+ bone marrow cells was performed using a monoclonal antibody to CD138 (Miltenyi Biotec, Germany) according to the manufacturer’s protocol. Fluorescent hybridization in situ of CD138+ cells was performed using DNA probes to detect translocations 14q32 / IgH, 8q24 / MYC, deletions 17p13 / TP53, 13q14, 1p32, amplification of 1q21 (amp1q21) and multiple trisomies (MetaSystems, Germany). High-risk cytogenetic aberrations included t(14;16), t(4;14), del17p13, amp1q21. Immunohistochemical examination of bone marrow trephine biopsy specimens using c-MAF antibody was performed in all patients. A heterogeneous or monomorphic nuclear reaction in more than 10 % of the tumor plasma cells was considered as positive c-MAF protein expression. Results . Cytogenetic examination of CD138+ bone marrow cells revealed high-risk aberrations in 24 patients, and standard risk cytogenetics was diagnosed in seven patients. c-MAF protein expression was detected in 29 % (6 of 21) of patients without plasmacytomas and in 70 % (7 of 10) of patients with plasmacytomas. c-MAF protein expression was strongly correlated with t(14;16) presence. In cases where it was absent, c-MAF protein expression in bone marrow was not observed, with the exception of one case. Thus, c-MAF protein expression in bone marrow was noted in 13 patients – twelve with t(14;16) and one patient with double hit myeloma (del17p13 and t(4;14)). No relationship was found between c-MAF protein expression and the presence / absence of plasmacytomas. In the presence of t(14;16), an atypical distribution of patients by paraprotein type was noted (immunoglobulins G, A, BJ myeloma occurred with the same frequency – 33.3 %). In MM with t(14;16), a tendency to more frequent detection of plasma cells in the peripheral blood was found (29 %); a quarter of patients had kidney damage. Plasmacytomas were detected in 50 % of patients with t(14;16), and in 25 % of them – extramedullary. Most patients with t(14;16) had stage III according to International Staging System (82 %). Conclusion . The expression of c-MAF protein strongly correlated with t(14;16) presence, however, no correlation with the presence / absence of plasmacytomas could be found. MM with t(14;16) is characterized by an aggressive phenotype. In the presence of t(14;16), there is a tendency towards a high frequency of kidney damage, detection of extramedullary plasmacytomas and plasma cells in the peripheral blood, and diagnosis at advanced stages of the disease.