KLF5 controls glutathione metabolism to suppress p190-BCR-ABL+ B-cell lymphoblastic leukemia.

Zhang C, D'Alessandro A, Wellendorf AM, Mohmoud F, Serrano-Lopez J, Perentesis JP, Komurov K, Alexe G, Stegmaier K, Whitsett JA, Grimes HL, Cancelas JA
Oncotarget 9 29665-29679 07/03/2018

Abstract

High-risk B-cell acute lymphoblastic leukemia (B-ALL) remains a therapeutic challenge despite advances in the use of tyrosine kinase inhibitors and chimeric-antigen-receptor engineered T cells. Lymphoblastic-leukemia precursors are highly sensitive to oxidative stress. KLF5 is a member of the Krüppel-like family of transcription factors. KLF5 expression is repressed in B-ALL, including BCR-ABL1+ B-ALL. Here, we demonstrate that forced expression of KLF5 in B-ALL cells bypasses the imatinib resistance which is not associated with mutations of BCR-ABL. Expression of Klf5 impaired leukemogenic activity of BCR-ABL1+ B-cell precursors

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