Title

Aberrant ARID5B expression and its association with Ikaros dysfunction in acute lymphoblastic leukemia.

Authors

Zheng Ge, Zhongda Hospital Southeast University
Qi Han, Zhongda Hospital Southeast University
Yan Gu, Zhongda Hospital Southeast University
Qinyu Ge, Southeast University
Jinlong Ma, Zhongda Hospital Southeast University
Justin Sloane, Thomas Jefferson University; Pennsylvania State University Medical CollegeFollow
Guofeng Gao, University of California-Davis Medical Center
Kimberly J. Payne, Zhongda Hospital Southeast University; Loma Linda University
Laszlo Szekely, Zhongda Hospital Southeast University; Karolinska University Hospital
Chunhua Song, Zhongda Hospital Southeast University; Pennsylvania State University Medical College
Sinisa Dovat, Zhongda Hospital Southeast University; Pennsylvania State University Medical College

Document Type

Article

Publication Date

11-1-2018

Comments

This article has been peer reviewed. It is the author’s final published version in Oncogenesis, Volume 7, Issue 11, November 2018, Article number 84.

The published version is available at https://doi.org/10.1038/s41389-018-0095-x. Copyright © Ge et al.

Abstract

Mutations and single nucleotide polymorphisms of AT-rich interactive domain-containing protein 5B (ARID5B) are involved in the oncogenesis of acute lymphoblastic leukemia (ALL) and treatment outcomes. However, ARID5B expression and clinical significance in ALL remain unclear. We found ARID5B is significantly down-regulated in ALL compared to healthy bone marrow controls. ARID5B also interacts with PHD finger protein 2 (PHF2). Low expression of ARID5B (ARID5B^low) or ARID5B and PHF2 (ARID5B^lowPHF2^low) is correlated with the markers of cell proliferation and poor prognosis in ALL patients. Ikaros directly regulates ARID5B expression in ALL. Restoring Ikaros function by Casein Kinase II inhibition also promotes ARID5B expression through recruitment of trimethylation of lysine 4 on histone H3 (H3K4me3) at its promoter region. In summary, our data show that aberrant expression of ARID5B and PHF2 is related to leukemic cell proliferation and several poor prognostic markers. Our data indicate ARID5B^low expression, particularly ARID5B^lowPHF2^low expression, is linked to Ikaros dysfunction and involved in the oncogenic effect of high-risk ALL, which may represent a high-risk subgroup of ALL. © 2018, The Author(s).

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Recommended Citation

Ge, Zheng; Han, Qi; Gu, Yan; Ge, Qinyu; Ma, Jinlong; Sloane, Justin; Gao, Guofeng; Payne, Kimberly J.; Szekely, Laszlo; Song, Chunhua; and Dovat, Sinisa, "Aberrant ARID5B expression and its association with Ikaros dysfunction in acute lymphoblastic leukemia." (2018). Abington Jefferson Health Papers. Paper 8.
https://jdc.jefferson.edu/abingtonfp/8

PubMed ID

30420689

Language

English