Correlation Between c-MYC Gene Expression and Response after Induction Therapy Among Patients with Newly Diagnosed Multiple Myeloma and Monoclonal Gammopathy Undetermined Significance

Introduction. Patients (pts) with oncopathology who have hyperexpression of c-MYC demonstrate low response to chemotherapy and poor prognosis. In our study we investigated the level of c-MYC gene expression in pts withmultiple myeloma (MM) and/or monoclonal gammopathy undetermined significance (MGUS) at the moment of MM/MGUS diagnosis.

Patients and Methods. 40 patients with newly diagnosed MM/MGUS and 9 healthy bone marrow donors (as a control group) were included in our study. The median age of patients with MM/MGUS was 56 years (29-77), donors - 32 years (24-41). The bone marrow collection for examination was done at the moment of diagnosis. The investigated material was divided into 2 samples: all mononuclears and separated CD138+ cells. Level of c-MYC expression was identified by quantitative real time PCR (qRT-PCR). The whole number of qRT-PCR analysis was 98. Induction therapy (VCD/PAD) was initiated for 36 patients with MM, 4 patients with MGUS remained under observation. Antitumor response was evaluated after induction therapy according to the IMGG criteria.

Results. From 98 samples among pts reliable results qRT-PCR and evaluated c-MYC expression were in 36 samples from total mononuclears and 17 from separated CD138+ cells. In all 18 samples from healthy donors: 9 from total mononuclear, and 9 from CD138+ cells results of qRT-PCR were reliable. Mean c-MYC expression level among MM/MGUS pts was 55.014 (2^ΔCt) in CD138+ cells and in samples from total mononuclears - 17.585 (2^ΔCt). In healthy donors the results were 7.183(2^ΔCt) and 1.907 (2^ΔCt) respectively. After induction therapy complete response (CR) was demonstrated 6 patients, very good partial response (VGPR) - in 7 patients, partial response (PR) - in 15 and other 5 pts were refractory. Mean c-MYC expression level in samples from separated CD138+ cells in pts with CR was-14.259 (2^ΔCt), with VGPR-38.314 (2^ΔCt), with PR-50.506 (2^ΔCt), and in refractory pts-181.271 (2^ΔCt), among patients with MGUS the level was 10.928 (2^ΔCt). In samples from mononuclears: 5.138, 30.355, 11.877, 38.911, 7.323 (2^ΔCt) respectively. Thus, response after induction therapy was worse among patients with high gene c-MYC expression (Figure 1 a). Such a correlation was not revealed in analysis of data from samples of total mononuclears (Figure 1 b).

Conclusion. Mean c-MYC gene expression level in CD138+ cells among MM/MGUS pts was higher than among healthy donors (p<0.05). Correlation between antitumor response and c-MYC gene expression level in CD138+ cells was found. Separation of cells to the membrane receptor of syndecan-1 (CD138 antigen) is necessary if we want to use the c-MYC gene expression level as a predictor of antitumor response.