Toggle Main Menu Toggle Search

Open Access padlockePrints

Lineage-inappropriate PAX5 expression in t(8;21) acute myeloid leukemia requires signaling-mediated abrogation of polycomb repression

Lookup NU author(s): Professor Olaf Heidenreich


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


The activation of B-cell-specific genes, such as CD19 and PAX5, is a hallmark of t(8; 21) acute myeloid leukemia (AML) which expresses the translocation product RUNX1/ETO. PAX5 is an important regulator of B-lymphoid development and blocks myeloid differentiation when ectopically expressed. To understand the molecular mechanism of PAX5 deregulation, we examined its chromatin structure and regulation in t(8; 21) AML cells, non-t(8; 21) myeloid precursor control cells, and pre-B cells. In non-t(8; 21) myeloid precursors, PAX5 is poised for transcription, but is repressed by polycomb complexes. In t(8; 21) AML, PAX5 is not directly activated by RUNX1/ETO, but expression requires constitutive mitogen-activated protein (MAP) kinase signaling. Using a model of t(8; 21) carrying an activating KIT mutation, we demonstrate that deregulated MAP kinase signaling in t(8; 21) AML abrogates the association of polycomb complexes to PAX5 and leads to aberrant gene activation. Our findings therefore suggest a novel role of activating tyrosine kinase mutations in lineage-inappropriate gene expression in AML.

Publication metadata

Author(s): Ray D, Kwon SY, Tagoh H, Heidenreich O, Ptasinska A, Bonifer C

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2013

Volume: 122

Issue: 5

Pages: 759-769

Print publication date: 24/04/2013

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology


DOI: 10.1182/blood-2013-02-482497


Altmetrics provided by Altmetric