TY - JOUR
T1 - Novel UHRF1-MYC Axis in Acute Lymphoblastic Leukemia
AU - Park, Soyoung
AU - Sater, Ali H.Abdel
AU - Fahrmann, Johannes F.
AU - Irajizad, Ehsan
AU - Cai, Yining
AU - Katayama, Hiroyuki
AU - Vykoukal, Jody
AU - Kobayashi, Makoto
AU - Dennison, Jennifer B.
AU - Garcia-Manero, Guillermo
AU - Mullighan, Charles G.
AU - Gu, Zhaohui
AU - Konopleva, Marina
AU - Hanash, Samir
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/9
Y1 - 2022/9
N2 - Ubiquitin-like, containing PHD and RING finger domain, (UHRF) family members are overexpressed putative oncogenes in several cancer types. We evaluated the protein abundance of UHRF family members in acute leukemia. A marked overexpression of UHRF1 protein was observed in ALL compared with AML. An analysis of human leukemia transcriptomic datasets revealed concordant overexpression of UHRF1 in B-Cell and T-Cell ALL compared with CLL, AML, and CML. In-vitro studies demonstrated reduced cell viability with siRNA-mediated knockdown of UHRF1 in both B-ALL and T-ALL, associated with reduced c-Myc protein expression. Mechanistic studies indicated that UHRF1 directly interacts with c-Myc, enabling ALL expansion via the CDK4/6-phosphoRb axis. Our findings highlight a previously unknown role of UHRF1 in regulating c-Myc protein expression and implicate UHRF1 as a potential therapeutic target in ALL.
AB - Ubiquitin-like, containing PHD and RING finger domain, (UHRF) family members are overexpressed putative oncogenes in several cancer types. We evaluated the protein abundance of UHRF family members in acute leukemia. A marked overexpression of UHRF1 protein was observed in ALL compared with AML. An analysis of human leukemia transcriptomic datasets revealed concordant overexpression of UHRF1 in B-Cell and T-Cell ALL compared with CLL, AML, and CML. In-vitro studies demonstrated reduced cell viability with siRNA-mediated knockdown of UHRF1 in both B-ALL and T-ALL, associated with reduced c-Myc protein expression. Mechanistic studies indicated that UHRF1 directly interacts with c-Myc, enabling ALL expansion via the CDK4/6-phosphoRb axis. Our findings highlight a previously unknown role of UHRF1 in regulating c-Myc protein expression and implicate UHRF1 as a potential therapeutic target in ALL.
KW - UHRF1
KW - acute lymphocytic leukemia
KW - c-Myc
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U2 - 10.3390/cancers14174262
DO - 10.3390/cancers14174262
M3 - Article
C2 - 36077796
AN - SCOPUS:85137827984
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 17
M1 - 4262
ER -