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 (ARID5Blow) or ARID5B and PHF2 (ARID5BlowPHF2low) 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 ARID5Blow expression, particularly ARID5BlowPHF2low 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.
| Original language | English (US) |
|---|---|
| Article number | 84 |
| Journal | Oncogenesis |
| Volume | 7 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2018 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cancer Research
Cite this
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Aberrant ARID5B expression and its association with Ikaros dysfunction in acute lymphoblastic leukemia. / Ge, Zheng; Han, Qi; Gu, Yan; Ge, Qinyu; Ma, Jinlong; Sloane, Justin; Gao, Guofeng; Payne, Kimberly J.; Szekely, Laszlo; Song, Chunhua; Dovat, Sinisa.
In: Oncogenesis, Vol. 7, No. 11, 84, 01.11.2018.Research output: Contribution to journal › Article
TY - JOUR
T1 - Aberrant ARID5B expression and its association with Ikaros dysfunction in acute lymphoblastic leukemia
AU - Ge, Zheng
AU - Han, Qi
AU - Gu, Yan
AU - Ge, Qinyu
AU - Ma, Jinlong
AU - Sloane, Justin
AU - Gao, Guofeng
AU - Payne, Kimberly J.
AU - Szekely, Laszlo
AU - Song, Chunhua
AU - Dovat, Sinisa
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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 (ARID5Blow) or ARID5B and PHF2 (ARID5BlowPHF2low) 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 ARID5Blow expression, particularly ARID5BlowPHF2low 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.
AB - 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 (ARID5Blow) or ARID5B and PHF2 (ARID5BlowPHF2low) 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 ARID5Blow expression, particularly ARID5BlowPHF2low 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.
UR - http://www.scopus.com/inward/record.url?scp=85056414388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056414388&partnerID=8YFLogxK
U2 - 10.1038/s41389-018-0095-x
DO - 10.1038/s41389-018-0095-x
M3 - Article
C2 - 30420689
AN - SCOPUS:85056414388
VL - 7
JO - Oncogenesis
JF - Oncogenesis
SN - 2157-9024
IS - 11
M1 - 84
ER -