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RNA-seq data of MV4-11, Kasumi-1, and KG-1 cells treated with HDAC8 inhibitor 22d 10 μM and control

ABSTRACT: We performed RNA sequencing on MV4-11, Kasumi-1, and KG-1 leukemia cell lines treated with HDAC8 inhibitor 22d at 10 μM and their respective control groups. The sequencing reads were processed to generate gene-level count matrices. This dataset provides processed count data for downstream gene expression analysis and comparison between treated and control conditions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE305655 | GEO | 2026/04/25

REPOSITORIES: GEO

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Project description:The prognosis of advanced stage neuroblastoma patients remains poor and, despite intensive therapy, the 5-year survival rate remains less than 50%. We previously identified histone deacetylase (HDAC) 8 as an indicator of poor clinical outcome and a selective drug target for differentiation therapy in vitro and in vivo. Here we performed kinome-wide RNAi screening to identify genes that are synthetically lethal with HDAC8 inhibitors. These experiments identified the neuroblastoma predisposition gene ALK as a candidate gene. Accordingly, the combination of the ALK/MET inhibitor crizotinib and selective HDAC8 inhibitors (3-6μM PCI-34051 or 10μM 20a) efficiently killed neuroblastoma cell lines carrying wildtype ALK (SK-N-BE(2)-C, IMR5/75), amplified ALK (NB-1), and those carrying the activating ALK F1174L mutation (Kelly), and, in cells carrying the activating R1275Q mutation (LAN-5), combination treatment decreased viable cell count. The effective dose of crizotinib in neuroblastoma cell lines ranged from 0.05μM (ALK-amplified) to 0.8μM (wildtype ALK). The combinatorial inhibition of ALK and HDAC8 also decreased tumor growth in an in vivo zebrafish xenograft model. Bioinformatic analyses revealed that the mRNA expression level of HDAC8 was significantly correlated with that of ALK in two independent patient cohorts, the Academic Medical Center cohort (n=88) and the German Neuroblastoma Trial cohort (n=649), and co-expression of both target genes identified patients with very poor outcome. Mechanistically, HDAC8 and ALK converge at the level of receptor tyrosine kinase (RTK) signaling and their downstream survival pathways, such as ERK signaling. Combination treatment of HDAC8 inhibitor with crizotinib efficiently blocked the activation of growth receptor survival signaling and shifted the cell cycle arrest and differentiation phenotype toward effective cell death of neuroblastoma cell lines, including sensitization of resistant models, but not of normal cells. These findings reveal combined targeting of ALK and HDAC8 as a novel strategy for the treatment of neuroblastoma.

Dataset Information

RNA-seq data of MV4-11, Kasumi-1, and KG-1 cells treated with HDAC8 inhibitor 22d 10 μM and control

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