Association between BCL2, BCL2 E17, MCL1 and BAX Protein Expression, Bone Marrow Microenvironment Histological Features, Clinical Presentation, Therapeutic Outcome, and the Overall Survival in Newly Diagnosed Multiple Myeloma

Abstract We evaluated the correlation between immunohistochemical BCL2, BCL2 E17, MCL1 (Bcl2-related protein family) and BAX (effector proapoptotic protein) expression intensity of staining in plasma cells (PC) MM patients (pts) who were eligible for autologous stem cell transplantation (ASCT) with DD4, CD8, FOXP3 positive Tregs lymphocytes bone marrow (BM) microenvironment, morphologic features PC, clinical parameters, outcomes. Immunohistochemical MCL1, BAX, CD4, Ki67 was performed BM biopsy 36 newly diagnosed ASCT 2012-2017 at University Hospital Merkur. Pearson's Spearmans's coefficients correlation, t-tests, one-way independent sample ANOVAs, mixed moderation analyses, chi-square tests independence Cox's proportional hazards used to analyze data. Median age pts 57 years (95% CI 52-60), 15 female equal distribution rISS I-III (12 pts). Twelve (33%) had high risk cytogenetics: del 13q34 (8 pts; 22%), 17p (5 pts, 13,8%), t(4; 14) (4 11.1%); t(16;14) 4 (11.1%) t(11;14). The median percentage PC (PC ptc) 60 45 - 80); 25 (69.4%) diffuse type infiltration (TI) BM; 23 (63.8%) grade differentiation (grade 2/3). 3% 2 4, range 1 80). 50 60) (63.8 %); E17 70) 33 (91.6%); 40 20 21 (58.3%); 17.5 6 40) 18 (50%). CD4 T-cells 8.5 18); CD8 24 37); 2, 31). Nineteen (52.7 %) underwent tandem ASCT, 34 (94.4%) received VCD induction; MP VD induction. Overall response rate (≥partial response) induction therapy 94.4%; ≥ very good partial 80.5%. 86.1%; complete 50%. overall survival time 35.40 months 26.61-165.39). Expression proteins significant positively, moderately strongly associated (p < 0.05), except BCL2E17 association (r (36) = 0.319, p 0.058). MCL-1 more correlated when well differentiated, .016). Higher pct higher BLC2 (t (34) 2.51, 0.017). Patients >10% a 2.04, 0.049). 2.63, 0.012). A found high-risk cytogenetic changes 2.09, 0.045). Cytoplasmic granular greater MLC than TI (χ (1) 6.60, Low BCL2E17, stage rISS1 compared rISS3 low ISS2 0.05). non-diffuse worse their (2) 6.39, 0.041). Although we observed number T-cell microenvironment aberrant CD4:CD8 ratio favor T-cell, it no impact on other variables study. s -0.417, 0.011), being contributed survivability 7.18, 0.007), while expression, as T-cells, did not predict > Results showed family members that may plays role application strategies therapy. Bcl-2 inhibits Bax but be result pre-condition or hormesis like responses stressful micro-environments serve increase apoptotic resistance. Further investigation Bcl2- biology its therapeutic outcomes is warranted. Disclosures Jaksic: Roche, Oktal-Pharma/Celtrion, Sandoz: Consultancy, Honoraria.