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Gene expression study of leukemic and premalignant hematopoietic tissues from NUP98-PHF23 (NP23) mice.

ABSTRACT: NUP98-PHF23 is oncogenic and results in a Hoxa/b + Meis1 overexpression in NP23 leukemias and in premalignant (clinically healthy) hematopoietic tissues. Gene expression profiles from AML, pre-T LBL and B-ALL were compared to wild type bone marrow, thymus and spleen tissues respectively. Similarly, gene expression profiles from premalignant (clinically healthy) NP23 bone marrow, thymus and spleen were compared to wild type bone marrow, thymus and spleen tissues respectively. 106A and 748T lymphoblastic cell lines were compared to wild type thymic tissue.

ORGANISM(S): Mus musculus

SUBMITTER: Yuelin Zhu

PROVIDER: E-GEOD-54787 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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NUP98-PHF23 is a chromatin-modifying oncoprotein that causes a wide array of leukemias sensitive to inhibition of PHD histone reader function.

Gough Sheryl M SM Lee Fan F Yang Fan F Walker Robert L RL Zhu Yeulin J YJ Pineda Marbin M Onozawa Masahiro M Chung Yang Jo YJ Bilke Sven S Wagner Elise K EK Denu John M JM Ning Yi Y Xu Bowen B Wang Gang Greg GG Meltzer Paul S PS Aplan Peter D PD

Cancer discovery 20140217 5

In this report, we show that expression of a NUP98-PHF23 (NP23) fusion, associated with acute myeloid leukemia (AML) in humans, leads to myeloid, erythroid, T-cell, and B-cell leukemia in mice. The leukemic and preleukemic tissues display a stem cell-like expression signature, including Hoxa, Hoxb, and Meis1 genes. The PHF23 plant homeodomain (PHD) motif is known to bind to H3K4me3 residues, and chromatin immunoprecipitation experiments demonstrated that the NP23 protein binds to chromatin at a ...[more]

PMID: 24535671

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