Abstract

Purpose This study aims to determine the influence of targeting araC-resistant acute myeloid leukemia by dual inhibition cyclin-dependent protein kinase (CDK9) and B-cell lymphoma-2 (Bcl-2). Method The c-Myc inhibitor 10058-F4 and the CDK9 inhibitor AZD4573 were used to determine the cell cycle arrest and apoptosis. Results 10058-F4 reduces c-Myc protein levels and suppresses HepG2 cell proliferation, possibly by upregulating cyclin-dependent kinase (CDK) inhibitors, p21WAF1, and reducing intracellular alpha-fetal protein (AFP) levels. Conclusion The combination of AZD4573 and 10058-F4 has a synergistic anti-araC-resistant AML activity, providing a solid database for the aforementioned scientific hypothesis.

Highlights

  • Hematopoietic stem cells can self-renew and differentiate, and their control regulates their proliferation speed [1, 2]

  • When hematopoietic stem cells show malignant proliferation, leukemic cells are characterized by abnormal proliferation, impaired differentiation, and blocked apoptosis. e proliferation and accumulation of leukemic cells are substantially held in the bone marrow and other hematopoietic tissues and proceed to infiltration in other body tissues and organs, affecting the normal physiological function of the human body

  • The apoptosis was induced by 10,058-F4 performing mitochondrial pathway activation, and downregulation of B-cell lymphoma-2 (Bcl-2), upregulation of Bax, cytochrome C release within the cytosol, and cleavage of caspase 3, 7, and 9 were observed

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Summary

Introduction

Hematopoietic stem cells can self-renew and differentiate, and their control regulates their proliferation speed [1, 2]. When hematopoietic stem cells show malignant proliferation, leukemic cells are characterized by abnormal proliferation, impaired differentiation, and blocked apoptosis. E proliferation and accumulation of leukemic cells are substantially held in the bone marrow and other hematopoietic tissues and proceed to infiltration in other body tissues and organs, affecting the normal physiological function of the human body. Erefore, it is urgent to develop more effective treatment strategies to enhance the therapeutic effect of leukemia and reduce mortality. The five-year overall survival in adult AML is only about 25% and about 65% in pediatric patients. Erefore, it is of great scientific and clinical importance to find new AML therapies, develop new therapeutic strategies to prolong the survival rate of AML patients, and improve their cure rates The five-year overall survival in adult AML is only about 25% and about 65% in pediatric patients. erefore, it is of great scientific and clinical importance to find new AML therapies, develop new therapeutic strategies to prolong the survival rate of AML patients, and improve their cure rates

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