Novel UHRF1-MYC Axis in Acute Lymphoblastic Leukemia

Soyoung Park; Ali H. Abdel Sater; Johannes F. Fahrmann; Ehsan Irajizad; Yining Cai; Hiroyuki Katayama; Jody Vykoukal; Makoto Kobayashi; Jennifer B. Dennison; Guillermo Garcia-Manero; Charles G. Mullighan; Zhaohui Gu; Marina Konopleva; Samir Hanash

doi:10.3390/cancers14174262

Cancers (Aug 2022)

Novel UHRF1-MYC Axis in Acute Lymphoblastic Leukemia

Soyoung Park,
Ali H. Abdel Sater,
Johannes F. Fahrmann,
Ehsan Irajizad,
Yining Cai,
Hiroyuki Katayama,
Jody Vykoukal,
Makoto Kobayashi,
Jennifer B. Dennison,
Guillermo Garcia-Manero,
Charles G. Mullighan,
Zhaohui Gu,
Marina Konopleva,
Samir Hanash

Affiliations

Soyoung Park: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Ali H. Abdel Sater: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Johannes F. Fahrmann: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Ehsan Irajizad: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Yining Cai: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Hiroyuki Katayama: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Jody Vykoukal: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Makoto Kobayashi: Department of Basic Pathology, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan
Jennifer B. Dennison: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Guillermo Garcia-Manero: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Charles G. Mullighan: Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Zhaohui Gu: Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Marina Konopleva: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Samir Hanash: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

DOI: https://doi.org/10.3390/cancers14174262
Journal volume & issue: Vol. 14, no. 17
p. 4262

Abstract

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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.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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