Robak Paweł, Szemraj Janusz, Mikulski Damian, Drozdz Izabela, Juszczak Karolina, Jarych Dariusz, Misiewicz Małgorzata, Kościelny Kacper, Fendler Wojciech, Robak Tadeusz
Department of Experimental Hematology, Medical University of Lodz, 93-510 Lodz, Poland.
Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland.
J Clin Med. 2021 Oct 28;10(21):5028. doi: 10.3390/jcm10215028.
While multiple myeloma (MM) treatment with proteasome inhibitors and other agents yields encouraging results, primary and secondary resistance remains an emerging problem. An important factor in such treatment resistance is the overexpression of several proteins. The present study comprehensively evaluates the expression of POMP, PSMB5, NRF2, XBP1, cMAF and MAFb proteins in plasma cells isolated from the bone marrow of 39 MM patients treated with bortezomib-based regimens using an enzyme-linked immunosorbent assay (ELISA). The proteins were selected on the basis of previous laboratory and clinical studies in bortezomib-treated MM patients. It was found that the expression of the investigated proteins did not significantly differ between bortezomib-sensitive and bortezomib-refractory patients. However, the expression of some proteins correlated with overall survival (OS); this was significantly shorter in patients with higher POMP expression (HR 2.8, 95% CI: 1.1-7.0, = 0.0277) and longer in those with higher MAFB expression (HR 0.32, 95% CI: 0.13-0.80, = 0.0147). Our results indicate that a high expression of POMP and MAFB in MM plasma cells may serve as predictors of OS in MM patients treated with bortezomib-based regimens. However, further studies are needed to determine the role of these factors in effective strategies for improving anti-myeloma therapy.
虽然蛋白酶体抑制剂和其他药物治疗多发性骨髓瘤（MM）取得了令人鼓舞的结果，但原发性和继发性耐药仍然是一个新出现的问题。这种治疗耐药的一个重要因素是几种蛋白质的过表达。本研究使用酶联免疫吸附测定（ELISA）全面评估了39例接受硼替佐米方案治疗的MM患者骨髓中分离的浆细胞中POMP、PSMB5、NRF2、XBP1、cMAF和MAFb蛋白的表达。这些蛋白质是根据先前对硼替佐米治疗的MM患者的实验室和临床研究选择的。结果发现，在硼替佐米敏感和硼替佐米难治患者之间，所研究蛋白质的表达没有显著差异。然而，一些蛋白质的表达与总生存期（OS）相关；POMP表达较高的患者OS明显较短（HR 2.8，95%CI：1.1 - 7.0，P = 0.0277），而MAFB表达较高的患者OS较长（HR 0.32，95%CI：0.13 - 0.80，P = 0.0147）。我们的结果表明，MM浆细胞中POMP和MAFB的高表达可能作为接受硼替佐米方案治疗的MM患者OS的预测指标。然而，需要进一步研究以确定这些因素在改善抗骨髓瘤治疗有效策略中的作用。
