TY - JOUR
T1 - The RUNX1/RUNX1T1 network
T2 - translating insights into therapeutic options
AU - Swart, Laura E
AU - Heidenreich, Olaf
N1 - Copyright © 2020 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - RUNX1/RUNX1T1 is the most common fusion gene found in acute myeloid leukemia. Seminal contributions by many different research groups have revealed a complex regulatory network promoting leukemic self-renewal and propagation. Perturbation of RUNX1/RUNX1T1 levels and its DNA binding affects chromatin accessibility and transcription factor occupation at multiple gene loci associated with changes in gene expression levels. Exploration of this transcriptional program by targeted RNAi screens uncovered a crucial role of RUNX1/RUNX1T1 in cell cycle progression by regulating CCND2. This dependency results in a high vulnerability toward inhibitors of CDK4 and CDK6 and suggests new avenues for therapeutic intervention against acute myeloid leukemia.
AB - RUNX1/RUNX1T1 is the most common fusion gene found in acute myeloid leukemia. Seminal contributions by many different research groups have revealed a complex regulatory network promoting leukemic self-renewal and propagation. Perturbation of RUNX1/RUNX1T1 levels and its DNA binding affects chromatin accessibility and transcription factor occupation at multiple gene loci associated with changes in gene expression levels. Exploration of this transcriptional program by targeted RNAi screens uncovered a crucial role of RUNX1/RUNX1T1 in cell cycle progression by regulating CCND2. This dependency results in a high vulnerability toward inhibitors of CDK4 and CDK6 and suggests new avenues for therapeutic intervention against acute myeloid leukemia.
KW - Animals
KW - Cell Cycle
KW - Core Binding Factor Alpha 2 Subunit/genetics
KW - Gene Expression Regulation, Leukemic
KW - Gene Regulatory Networks
KW - Humans
KW - Leukemia, Myeloid, Acute/genetics
KW - Oncogene Proteins, Fusion/genetics
KW - Protein Interaction Maps
KW - RUNX1 Translocation Partner 1 Protein/genetics
KW - Transcriptional Activation
UR - http://www.scopus.com/inward/record.url?scp=85097039310&partnerID=8YFLogxK
U2 - 10.1016/j.exphem.2020.11.005
DO - 10.1016/j.exphem.2020.11.005
M3 - Review article
C2 - 33217477
SN - 0301-472X
VL - 94
SP - 1
EP - 10
JO - Experimental hematology
JF - Experimental hematology
ER -