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Figure S3 from The CDK4/6 Inhibitor Palbociclib Synergizes with ATRA to Induce Differentiation in AML

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posted on 2024-07-02, 07:41 authored by Linhui Hu, Qian Li, Jiyu Wang, Huiping Wang, Xiyang Ren, Keke Huang, Yangyang Wang, Xue Liang, Lianfang Pu, Shudao Xiong, Zhimin Zhai

Figure S3. Knockdown CDK4 and CDK6 via siRNA in HL-60 and molm13 cells (A). The effect of palbociclib and ATRA combination on cell cycle(B), cell proliferation (C), and cell apoptosis (D). * Represent when it compares with the control group, P<0.05. # Represent when it compares with the ATRA group, P<0.05.

Funding

National Natural Science Foundation of China (NSFC)

Anhui Provincial Department of Education (安徽省教育厅)

Anhui Medical University (AHMU)

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ARTICLE ABSTRACT

Differentiation therapy based on ATRA almost cured acute promyelocytic leukemia (APL). However, it is disappointing that ATRA is not effective against other acute myeloid leukemia (AML) subtypes. Developing new and effective anti-AML therapies that promote leukemia differentiation is necessary. The CDK4/6-cyclin D pathway is a key initiator of the G1–S phase transition, which determines cell fate. Herein, we investigated whether the CDK4/6 inhibitor palbociclib would synergize with ATRA to promote leukemia differentiation in vitro and in vivo. Our findings revealed that CDK4/6-cyclin D pathway genes were aberrantly expressed in AML, and we observed that palbociclib sensitized AML cells to ATRA-induced morphologic, biochemical, and functional changes indicative of myeloid differentiation. The combination of palbociclib and ATRA attenuated AML cell expansion in vivo. These enhanced differentiation effects may be associated with the regulation of transcription factors, including RARα, E2F1, and STAT1. Overall, our findings demonstrate that CDK4/6 inhibition sensitizes AML cells to ATRA and could guide the development of novel therapeutic strategies for patients with AML.

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    Molecular Cancer Therapeutics

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