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

Zheng Ge; Qi Han; Yan Gu; Qinyu Ge; Jinlong Ma; Justin Sloane; Guofeng Gao; Kimberly J Payne; Laszlo Szekely; Chunhua Song; Sinisa Dovat

doi:10.1038/s41389-018-0095-x

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

Oncogenesis. 2018 Nov 12;7(11):84. doi: 10.1038/s41389-018-0095-x.

Authors

Zheng Ge^{1

2}, Qi Han^{3

4}, Yan Gu^{3

4}, Qinyu Ge⁵, Jinlong Ma^{3

4}, Justin Sloane^{6

7}, Guofeng Gao⁸, Kimberly J Payne^{4

9}, Laszlo Szekely^{4

10}, Chunhua Song^{11

12}, Sinisa Dovat^{13

14}

Affiliations

¹ Department of Hematology, Zhongda Hospital Southeast University, Institute of Hematology Southeast University, 210009, Nanjing, China. Janege879@hotmail.com.
² International Cooperative Leukemia Group and International Cooperative Laboratory of Hematology, Zhongda Hospital Southeast University, 210009, Nanjing, China. Janege879@hotmail.com.
³ Department of Hematology, Zhongda Hospital Southeast University, Institute of Hematology Southeast University, 210009, Nanjing, China.
⁴ International Cooperative Leukemia Group and International Cooperative Laboratory of Hematology, Zhongda Hospital Southeast University, 210009, Nanjing, China.
⁵ State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 210096, Nanjing, China.
⁶ Abington Hospital, Jefferson Health, Abington, PA, 19001, USA.
⁷ Department of Pediatrics, Pennsylvania State University Medical College, Hershey, PA17033, USA.
⁸ Department of Pathology and Laboratory Medicine, University of California-Davis Medical Center, Sacramento, CA, 95817, USA.
⁹ Department of Pathology and Human Anatomy, Loma Linda University, Loma Linda, CA, 92350, USA.
¹⁰ Department of Medicine, Laboratory of Clinical Pathology and cytology, Karolinska University Hospital, Solna, L2:04, SE-171 76, Stockholm, Sweden.
¹¹ International Cooperative Leukemia Group and International Cooperative Laboratory of Hematology, Zhongda Hospital Southeast University, 210009, Nanjing, China. csong@pennstatehealth.psu.edu.
¹² Department of Pediatrics, Pennsylvania State University Medical College, Hershey, PA17033, USA. csong@pennstatehealth.psu.edu.
¹³ International Cooperative Leukemia Group and International Cooperative Laboratory of Hematology, Zhongda Hospital Southeast University, 210009, Nanjing, China. sdovat@pennstatehealth.psu.edu.
¹⁴ Department of Pediatrics, Pennsylvania State University Medical College, Hershey, PA17033, USA. sdovat@pennstatehealth.psu.edu.

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.

Abstract

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