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Abstract: Objective To investigate the molecular mechanism by which myeloid cell leukemiafactor 1 ( MCL1) promotes the resistance of acute T lymphoblastic leukemia ( T-ALL) cells tovenetoclax. Methods T-ALL parental cell line Jurkat and T-ALL venetoclax-resistant cell line Jurkat / VEN were cultured, and small interfering RNA targeting MCL1 (si-MCL1) and negative control (si-NC) were transfected into Jurkat / VEN cells. RT-qPCR and Western blotting were used to detect the expression level of MCL1 in transfected cells to verify the transfection effect. The expression levels of GSK3β, phosphorylated GSK3β ( p-GSK3β), β-catenin, c-Myc, and cyclin D1 were detected by Western blotting. Jurkat / VEN cells were divided into 4 groups: control group, siNC group, si-MCL1 group, si-MCL1 + CHIR-99021 group. The CCK-8 method was used to detect the survival rate of Jurkat / VEN cells in each group under different concentrations (0, 100, 200, 300, 400, 500 nmol / L) of venetoclax, the colony formation assay was used to detect the numberof colonies formed in each group, and the flow cytometry was used to detect the apoptosisrate. Results Compared with those in the Jurkat cells, the protein expression level of MCL1 in theJurkat / VEN cells was increased (P < 0. 05), the expression level of GSK3β was decreased (P <0. 05), and the expression levels of p-GSK3β, β-catenin, c-Myc and Cyclin D1 were increased(P < 0. 05) . Compared with those in the control group and si-NC group, the mRNA and proteinexpression levels of MCL1 were decreased in the si-MCL1 group (P < 0. 05), the expression levelof GSK3β was increased (P < 0. 05), and the expression levels of p-GSK3β, β-catenin, c-Mycand Cyclin D1 proteins were decreased (P< 0. 05) . Compared with those in the control group andsi-NC group, the survival rate after venetoclax treatment and the value of IC50 were decreased in thesi-MCL1 group (P< 0. 05), the number of colonies was decreased (P< 0. 05), and the apoptosisrate was increased (P< 0. 05) . Compared with those in the si-MCL1 group, the survival rate aftervenetoclax treatment and the value of IC50 were increased in the si-MCL1 + CHIR-99021 group (P<0. 05), the number of colonies was increased (P < 0. 05), and the apoptosis rate was decreased(P< 0. 05) . Conclusion Interference in MCL1 expression can reduce the drug resistance ofJurkat / VEN cells to venetoclax, which may be achieved by blocking the GSK-3β / Wnt / β-cateninsignaling axis.

Key words: acute T lymphocytic leukemia, myeloid cell leukemia factor 1, venetoclax, drug resistance