FOXM1 is overexpressed in B-acute lymphoblastic leukemia (B-ALL) and its inhibition sensitizes B-ALL cells to chemotherapeutic drugs

International Journal of Oncology
Francesca ConsolaroGiampietro Viola

Abstract

The Forkhead box protein M1 (FOXM1) is a transcription factor that plays a central role in the regulation of cell cycle, proliferation, DNA repair, and apoptosis. FOXM1 is overexpressed in many human tumors and its upregulation has been linked to high proliferation rates and poor prognosis. We therefore studied the role of FOXM1 in B-lymphoblastic leukemia (B-ALL) in order to understand whether FOXM1 could be a key target for leukemia therapy. RT-PCR and western blot analysis were carried out in a small cohort of pediatric B-ALL patients to evaluate FOXM1 levels. To assess its biological relevance, its expression was down-modulated by transient RNA interference in B-ALL cell lines (REH and NALM-6). Our results show that FOXM1 expression is higher in both B-ALL patients and cell lines when compared to PBMC or normal B-cells (CD19+) from healthy donors. Furthermore, blocking FOXM1 activity in two B-ALL cell lines, by either knockdown or treatment with the FOXM1 inhibitor thiostrepton, causes significant decrease in their cell proliferation. This decrease in cell proliferation was coupled with both an induction of the G2/M cell cycle arrest and with a reduction in the S phase population. Finally, we noted how thiostrepton synergis...Continue Reading

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Citations

Nov 23, 2018·BMC Cancer·Chunyan GuSiegfried Janz
Apr 14, 2016·Oncotarget·Fergal C Kelleher, Hazel O'Sullivan
Feb 11, 2016·Molecular Medicine Reports·Hongmei ZhangXiaoqian Zhang
Oct 27, 2018·International Journal of Molecular Sciences·Duc-Hiep BachSang Kook Lee

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Methods Mentioned

BETA
electrophoresis
X-ray
transfection
flow cytometry
xenograft

Software Mentioned

Calcusyn

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