Paradoxical enhancement of leukemogenesis in acute myeloid leukemia with moderately attenuated RUNX1 expressions

Blood Advances
Ken MoritaYasuhiko Kamikubo

Abstract

Besides being a classical tumor suppressor, runt-related transcription factor 1 (RUNX1) is now widely recognized for its oncogenic role in the development of acute myeloid leukemia (AML). Here we report that this bidirectional function of RUNX1 possibly arises from the total level of RUNX family expressions. Indeed, analysis of clinical data revealed that intermediate-level gene expression of RUNX1 marked the poorest-prognostic cohort in relation to AML patients with high- or low-level RUNX1 expressions. Through a series of RUNX1 knockdown experiments with various RUNX1 attenuation potentials, we found that moderate attenuation of RUNX1 contributed to the enhanced propagation of AML cells through accelerated cell-cycle progression, whereas profound RUNX1 depletion led to cell-cycle arrest and apoptosis. In these RUNX1-silenced tumors, amounts of compensative upregulation of RUNX2 and RUNX3 expressions were roughly equivalent and created an absolute elevation of total RUNX (RUNX1 + RUNX2 + RUNX3) expression levels in RUNX1 moderately attenuated AML cells. This elevation resulted in enhanced transactivation of glutathione S-transferase α 2 (GSTA2) expression, a vital enzyme handling the catabolization of intracellular reactive ox...Continue Reading

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Citations

Jun 9, 2018·Cancer Science·Yasuhiko Kamikubo
Dec 10, 2017·Hematology·Jaroslaw P Maciejewski, Suresh K Balasubramanian
Nov 13, 2020·Pediatric Blood & Cancer·Tomoo DaifuYasuhiko Kamikubo
Jan 4, 2021·Stem Cell Research·Nikolaos Spyrou, Eirini P Papapetrou

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