The RUNX1/RUNX1T1 network: translating insights into therapeutic options

Laura E Swart; Olaf Heidenreich

doi:10.1016/j.exphem.2020.11.005

The RUNX1/RUNX1T1 network: translating insights into therapeutic options

Laura E Swart, Olaf Heidenreich

Group Heidenreich

Research output: Contribution to journal › Review article › peer-review

19 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1-10
Number of pages	10
Journal	Experimental hematology
Volume	94
DOIs	https://doi.org/10.1016/j.exphem.2020.11.005
Publication status	Published - Feb 2021

Keywords

Animals
Cell Cycle
Core Binding Factor Alpha 2 Subunit/genetics
Gene Expression Regulation, Leukemic
Gene Regulatory Networks
Humans
Leukemia, Myeloid, Acute/genetics
Oncogene Proteins, Fusion/genetics
Protein Interaction Maps
RUNX1 Translocation Partner 1 Protein/genetics
Transcriptional Activation

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10.1016/j.exphem.2020.11.005

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title = "The RUNX1/RUNX1T1 network: translating insights into therapeutic options",

abstract = "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.",

keywords = "Animals, Cell Cycle, Core Binding Factor Alpha 2 Subunit/genetics, Gene Expression Regulation, Leukemic, Gene Regulatory Networks, Humans, Leukemia, Myeloid, Acute/genetics, Oncogene Proteins, Fusion/genetics, Protein Interaction Maps, RUNX1 Translocation Partner 1 Protein/genetics, Transcriptional Activation",

author = "Swart, {Laura E} and Olaf Heidenreich",

year = "2021",

month = feb,

doi = "10.1016/j.exphem.2020.11.005",

language = "English",

volume = "94",

pages = "1--10",

journal = "Experimental hematology",

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T1 - The RUNX1/RUNX1T1 network

T2 - translating insights into therapeutic options

AU - Swart, Laura E

AU - Heidenreich, Olaf

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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

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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 -

The RUNX1/RUNX1T1 network: translating insights into therapeutic options

Abstract

Keywords

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