RNA-binding protein IGF2BP1 maintains leukemia stem cell properties by regulating HOXB4, MYB, and ALDH1A1

Irina A. Elcheva, Tyler Wood, Kathryn Chiarolanzio, Bryan Chim, Madeline Wong, Vikash Singh, Chethana P. Gowda, Qingli Lu, Markus Hafner, Sinisa Dovat, Zhenqiu Liu, Stefan A. Muljo, Vladimir S. Spiegelman

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an oncofetal protein expressed in various cancers including leukemia. In this study, we assessed the role of IGF2BP1 in orchestrating leukemia stem cell properties. Tumor-initiating potential, sensitivity to chemotherapeutic agents, and expression of cancer stem cell markers were assessed in a panel of myeloid, B-, and T-cell leukemia cell lines using gain- and loss-of-function systems, cross-linking immunoprecipitation (CLIP), and photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CLIP) techniques. Here, we report that genetic or chemical inhibition of IGF2BP1 decreases leukemia cells’ tumorigenicity, promotes myeloid differentiation, increases leukemia cell death, and sensitizes leukemia cells to chemotherapeutic drugs. IGF2BP1 affects proliferation and tumorigenic potential of leukemia cells through critical regulators of self-renewal HOXB4 and MYB and through regulation of expression of the aldehyde dehydrogenase, ALDH1A1. Our data indicate that IGF2BP1 maintains leukemia stem cell properties by regulating multiple pathways of stemness through transcriptional and metabolic factors.

Original languageEnglish (US)
Pages (from-to)1354-1363
Number of pages10
JournalLeukemia
Volume34
Issue number5
DOIs
StatePublished - May 1 2020

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

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