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The Class IIA Histone Deacetylase (HDAC) Inhibitor TMP269 Downregulates Ribosomal Proteins and Has Anti-Proliferative and Pro-Apoptotic Effects on AML Cells

Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by altered myeloid progenitor cell proliferation and differentiation. As in many other cancers, epigenetic transcriptional repressors such as histone deacetylases (HDACs) are dysregulated in AML. Here, we investigated (1) HDAC gene expression in AML patients and in different AML cell lines and (2) the effect of treating AML cells with the specific class IIA HDAC inhibitor TMP269, by applying proteomic and comparative bioinformatic analyses. We also analyzed cell proliferation, apoptosis, and the cell-killing capacities of TMP269 in combination with venetoclax compared to azacitidine plus venetoclax, by flow cytometry. Our results demonstrate significantly overexpressed class I and class II HDAC genes in AML patients, a phenotype which is conserved in AML cell lines. In AML MOLM-13 cells, TMP269 treatment downregulated a set of ribosomal proteins which are overexpressed in AML patients at the transcriptional level. TMP269 showed anti-proliferative effects and induced additive apoptotic effects in combination with venetoclax. We conclude that TMP269 exerts anti-leukemic activity when combined with venetoclax and has potential as a therapeutic drug in AML.

 

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The study investigated the expression of histone deacetylases (HDACs) in acute myeloid leukemia (AML) and the effect of the class IIA HDAC inhibitor TMP269 on AML cells. The results showed that class I and class II HDAC genes were significantly overexpressed in AML patients and cell lines. TMP269 treatment downregulated a set of ribosomal proteins in AML MOLM-13 cells, which are overexpressed in AML patients. TMP269 also exhibited anti-proliferative and apoptotic effects in combination with venetoclax. The study suggests that TMP269 has potential as a therapeutic drug for AML, particularly when used in combination with venetoclax.

Related Products

Cat.No. Product Name Information
S7324 TMP269 TMP269 is a potent, selective class IIa HDAC inhibitor with IC50 of 157 nM, 97 nM, 43 nM and 23 nM for HDAC4, HDAC5, HDAC7 and HDAC9, respectively.

Related Targets

HDAC