Increased MCL-1 expression predicts poor prognosis and disease recurrence in acute myeloid leukemia

MCL-1 表达增加预示急性髓系白血病预后不良和疾病复发

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作者:Xi-Xi Li, Jing-Dong Zhou, Xiang-Mei Wen, Ting-Juan Zhang, De-Hong Wu, Zhao-Qun Deng, Zhi-Hui Zhang, Xin-Yue Lian, Pin-Fang He, Xin-Yu Yao, Jiang Lin, Jun Qian

Background

Altered expression of the BCL-2 family member MCL-1 has been linked to the progression and outcome of various malignancies. Recently, MCL-1 inhibitor S63845 was reported to kill MCL-1-dependent cancer cells and has potential value in clinical application.

Conclusion

Our findings suggest that higher expression of MCL-1 predicts poor prognosis and can be used for disease monitoring.

Purpose

Herein, we reported MCL-1 expression pattern in Chinese de novo acute myeloid leukemia (AML) and its impact on prognosis and may provide theoretical basis for AML patients using MCL-1 inhibitor in clinics. Real-time quantitative PCR was carried out to detect the transcript of MCL-1 in AML patients.

Results

MCL-1 expression was significantly up-regulated in AML compared with controls (P=0.042). We divided the patients into two groups (higher and lower expression of MCL-1) based on the median level. Among both non-acute promyelocytic leukemia (APL) and cytogenetically normal AML (CN-AML), patients with higher expression of MCL-1 correlated with lower complete remission (CR) rate (P=0.031 and 0.004, respectively) and shorter overall survival (OS) time (P=0.008 and 0.004, respectively) compared with those with lower expression of MCL-1. Meanwhile, Cox regression analyses revealed that overexpression of MCL-1 acted as an independent risk factor for OS in non-APL patients and CN-AML patients (P=0.011 and 0.045, respectively). In follow-up patients, MCL-1 expression level decreased after CR compared with newly diagnosis time (P=0.020) and increased after relapse (P=0.004).

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