SALL1 expression in acute myeloid leukemia
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Huda Salman1,2, Xiao Shuai2,3,*, Anh Thu Nguyen-Lefebvre1,*, Banabihari Giri1, Mingqiang Ren1, Michael Rauchman4, Lynn Robbins4, Wei Hou2, Hasan Korkaya1 and Yupo Ma2
1Georgia Regent University Cancer Center, Augusta, GA, USA
2Present address: Stony Brook University Cancer Center, Stony Brook, NY, USA
3Department of Hematology, West China hospital of Sichuan University, Chengdu, P.R. China
4Department of Nephrology, Saint Louis University, St Louis, MO, USA
*These authors contributed equally to this work
Huda Salman, email: [email protected]
Keywords: SALL1; AML
Received: August 18, 2017 Accepted: October 25, 2017 Published: December 15, 2017
Similar signaling pathways could operate in both normal hematopoietic stem and progenitor cells (HSPCs) and leukemia stem cells (LSCs). Thus, targeting LSCs signaling without substantial toxicities to normal HSPCs remains challenging. SALL1, is a member of the transcriptional network that regulates stem cell pluripotency, and lacks significant expression in most adult tissues, including normal bone marrow (NBM). We examined the expression and functional characterization of SALL1 in NBM and in acute myeloid leukemia (AML) using in vitro and in vivo assays. We showed that SALL1 is expressed preferentially in LSCs- enriched CD34+CD38- cell subpopulation but not in NBM. SALL1 inhibition resulted in decreased cellular proliferation and in inferior AML engraftment in NSG mice and it was also associated with upregulation of PTEN and downregulation of m-TOR, β-catenin, and NF- қB expression. These findings suggest that SALL1 inhibition interrupts leukemogenesis. Further studies to validate SALL1 as a potential biomarker for minimal residual disease (MRD) and to determine SALL1’s role in prognostication are ongoing. Additionally, pre-clinical evaluation of SALL1 as a therapeutic target in AML is warranted.
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