SALL1 expression in acute myeloid leukemia

Huda Shafic Salman, Xiao Shuai, Anh Thu Nguyen, Banabihari Giri, Mingqiang Ren, Michael Rauchman, Lynn Robbins, Wei Hou, Hasan Korkaya, Yupo Ma

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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-κB 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.

Original languageEnglish (US)
Pages (from-to)7442-7452
Number of pages11
JournalOncotarget
Volume9
Issue number7
DOIs
StatePublished - Jan 26 2018

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Hematopoietic Stem Cells
Acute Myeloid Leukemia
Stem Cells
Leukemia
Bone Marrow
Catenins
Gene Regulatory Networks
Residual Neoplasm
Up-Regulation
Down-Regulation
Biomarkers
Cell Proliferation
Therapeutics

Keywords

  • AML
  • SALL1

ASJC Scopus subject areas

  • Oncology

Cite this

Salman, H. S., Shuai, X., Nguyen, A. T., Giri, B., Ren, M., Rauchman, M., ... Ma, Y. (2018). SALL1 expression in acute myeloid leukemia. Oncotarget, 9(7), 7442-7452. https://doi.org/10.18632/oncotarget.23448

SALL1 expression in acute myeloid leukemia. / Salman, Huda Shafic; Shuai, Xiao; Nguyen, Anh Thu; Giri, Banabihari; Ren, Mingqiang; Rauchman, Michael; Robbins, Lynn; Hou, Wei; Korkaya, Hasan; Ma, Yupo.

In: Oncotarget, Vol. 9, No. 7, 26.01.2018, p. 7442-7452.

Research output: Contribution to journalArticle

Salman, HS, Shuai, X, Nguyen, AT, Giri, B, Ren, M, Rauchman, M, Robbins, L, Hou, W, Korkaya, H & Ma, Y 2018, 'SALL1 expression in acute myeloid leukemia', Oncotarget, vol. 9, no. 7, pp. 7442-7452. https://doi.org/10.18632/oncotarget.23448
Salman HS, Shuai X, Nguyen AT, Giri B, Ren M, Rauchman M et al. SALL1 expression in acute myeloid leukemia. Oncotarget. 2018 Jan 26;9(7):7442-7452. https://doi.org/10.18632/oncotarget.23448
Salman, Huda Shafic ; Shuai, Xiao ; Nguyen, Anh Thu ; Giri, Banabihari ; Ren, Mingqiang ; Rauchman, Michael ; Robbins, Lynn ; Hou, Wei ; Korkaya, Hasan ; Ma, Yupo. / SALL1 expression in acute myeloid leukemia. In: Oncotarget. 2018 ; Vol. 9, No. 7. pp. 7442-7452.
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