Novel UHRF1-MYC Axis in Acute Lymphoblastic Leukemia.
Soyoung ParkAli Hussein Abdel SaterJohannes F FahrmannEhsan IrajizadYining CaiHiroyuki KatayamaJody VykoukalMakoto KobayashiJennifer B DennisonGuillermo Garcia-ManeroCharles G MullighanZhaohui GuMarina KonoplevaSamir HanashPublished in: Cancers (2022)
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.
Keyphrases
- acute lymphoblastic leukemia
- acute myeloid leukemia
- endothelial cells
- transcription factor
- cell proliferation
- allogeneic hematopoietic stem cell transplantation
- single cell
- squamous cell carcinoma
- cell cycle
- small molecule
- rna seq
- bone marrow
- protein protein
- climate change
- risk assessment
- squamous cell
- hyaluronic acid
- pluripotent stem cells