The combination of C-Myc rearrangement and 1q21 gain is associated with poor prognosis in multiple myeloma.

Yuanyuan Jin, Xiaochen Yu, Jianhua Du, Hui Li, Wenjiao Tang, Congwei Jia, Yunyan Zan, Miao Chen, Yanbin Zhang, Minhong Yu, Weiqi Rong, Daobin Zhou, Junling Zhuang

Annals of hematology 2021 May

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The prognostic value of chromosomal 1q21 gain in newly diagnosed multiple myeloma (NDMM) remains controversial. Add-on Myc aberrations may further worsen the outcome. To investigate whether specific genes located at the 1q21 region, such as myeloid cell leukemia 1 (Mcl-1), are involved in NDMM progression, we examined bone marrow cytogenetic abnormalities in 153 patients with NDMM by fluorescence in situ hybridization. Their response to treatment and survival was also analyzed. C-Myc and Mcl-1 expressions in bone marrow samples were analyzed by RT-PCR. The expression of Mcl-1 was evaluated in bone marrow sections by immunohistochemistry. MM cell lines were transfected with Mcl-1 siRNA. 1q21 gain was present in 55/153 (35.9%) patients and strongly associated with Myc rearrangement (31/153, 20.3%, P = 0.004). A positive correlation was observed between Myc and Mcl-1 mRNA levels in bone marrow cells from 47 patients (r = 0.57, P < 0.001). The combination of 1q21 gain and Myc rearrangement was associated with poorer overall survival than Myc rearrangement alone (16.8 vs. 27.9 months, P = 0.077) or 1q21 gain alone (16.8 vs. 60.7 months, P < 0.01). High Mcl-1 protein expression in bone marrow plasma cells was associated with Myc rearrangement. Mcl-1 silencing by siRNA inhibited Myc protein expression in three myeloma cell lines. Treatment with the small-molecule Mcl-1 inhibitor, UMI-77, produced similar results. Overall, the combination of Myc rearrangement and 1q21 gain was associated with particularly poor prognosis in patients with MM. Furthermore, our data are consistent with Mcl-1-dependent Myc protein activation.

Citation

Yuanyuan Jin, Xiaochen Yu, Jianhua Du, Hui Li, Wenjiao Tang, Congwei Jia, Yunyan Zan, Miao Chen, Yanbin Zhang, Minhong Yu, Weiqi Rong, Daobin Zhou, Junling Zhuang. The combination of C-Myc rearrangement and 1q21 gain is associated with poor prognosis in multiple myeloma. Annals of hematology. 2021 May;100(5):1251-1260