<p>Increased <em>MCL-1</em> expression predicts poor prognosis and disease recurrence in acute myeloid leukemia</p>

Abstract

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

Assessment of the Diagnostic Potential of miR-29a-3p and miR-92a-3p as Circulatory Biomarkers in Acute Myeloid Leukemia

“…However, El-Halawani et al, (2017) reported high level of miRNA29a expression in Flt3-ITD+ as compared to the Flt3-ITD. Moreover, the correlation analysis revealed the presence of significant positive direct association between levels of mir-29a and mir-92a (r=0.533, p = 0.001) and negative correlation with MCL1 transcript level was observed (r= -0.606, p<0.001, r= -0.339, p=0.043, respectively) and this was consistent with other studies that showed that down-regulation of miR-29a and miR-29b accompanied by up-regulation of the anti-apoptotic gene MCL1 transcripts as well as Bcl 2 in myeloid leukemias and such increase reflects poor prognosis (Li et al, 2019). In our study, no relationship was found between Mcl-1 expression and age, sex, TLC, PLT, BM blasts, cell surface antigens or FLT3-ITD.…”

MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents

“…In accordance with these findings, MCL-1 upregulation is frequently found at disease recurrence [ 127 ] and high levels of MCL-1 are linked to poor outcome. [ 128 ]. In contrast to this, mitochondrial priming measured by BH3 mimetic peptides showed primary AML cells from both refractory and sensitive patients responded more to the BAD BH3 peptide, which suggested a specific dependence on BCL-2 or BCL-w for these cells' survival.…”

Structure–Activity Relationships and Molecular Docking Analysis of Mcl-1 Targeting Renieramycin T Analogues in Patient-derived Lung Cancer Cells

“…The protein levels of Bcl-2 and Mcl-1 in various types of tumor tissues were found to be frequently augmented at a higher ratio than the other anti-apoptotic proteins in the Bcl-2 family [26]. In particular, increased expressions of Bcl-2 and Mcl-1 reflect a poor prognosis for many malignancies, including lung cancer [37][38][39]. Not only is their increased expression critical for oncogenesis and cancer progression, but these proteins are also involved in conferring chemotherapeutic drug resistance [35,[40][41][42][43].…”