The Anti-leukemic Effect of the Inhibition of Spleen Tyrosine Kinase and Histone Deacetylase Enzyme Inhibition on the FLT3-ITD(+) Acute Myeloid Leukemia Cells

Authors : Merve Şansaçar, Emel Başak Gencer Akcok

Pages : 708-721

View : 32 | Download : 17

Publication Date : 2025-08-30

Article Type : Research Paper

Abstract :Spleen Tyrosine Kinase (Syk) crosstalk with paramount signaling pathways which has a major contribution in the progress of acute myeloid leukemia (AML) such as PI3K, NFκB and JAK/STAT signaling pathways. Several studies recorded that deregulated Histone Deacetylase (HDAC) enzymes are involved in the pathogenesis of AML. The study aims to reveal the effect of Syk and HDAC co-inhibition on MOLM-13 and MV4-11 AML cells which are harboring the receptor of FMS-like Tyrosine Kinase\\\'s (FLT3) Internal Tandem Duplication (ITD). AML cells were incubated using both R406 and HDAC inhibitors alone and in combination, and increasing concentrations of R406 and HDAC inhibitors revealed a significant reduction of MOLM-13 and MV4-11 cells’ viability using MTT cell viability test. Furthermore, the combination of R406 and VPA resulted in a reduction in the proliferation of both cells correlated with the synergistic effect of the two drugs revealed by the combination index (CI). Moreover, investigating apoptosis for the combined administration of drugs resulted in induced apoptosis in AML cells using Annexin-V/PI double staining. We observed also changes in the mRNA expression level of MYC after combination treatment via Real-time PCR analysis. Even though further studies are needed, targeting Syk and HDAC enzymes in AML cells may be a good strategy in the treatment of patients suffering from AML with FLT3 ITD (+) mutation.
Keywords : Lösemi, Dalak tirozin kinazı, Histon deasetilaz enzimleri, Kombinasyon tedavisi, R406, HDAC inhibitörleri

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