hsa-mir183/EGR1–mediated regulation of E2F1 is required for CML stem/progenitor cell survival

Academic Article

Abstract

  • © 2018 by The American Society of Hematology. Chronic myeloid leukemia (CML) stem/progenitor cells (SPCs) express a transcriptional program characteristic of proliferation, yet can achieve and maintain quiescence. Understanding the mechanisms by which leukemic SPCs maintain quiescence will help to clarify how they persist during long-term targeted treatment. We have identified a novel BCR-ABL1 protein kinase–dependent pathway mediated by the upregulation of hsa-mir183, the downregulation of its direct target early growth response 1 (EGR1), and, as a consequence, upregulation of E2F1. We show here that inhibition of hsa-mir183 reduced proliferation and impaired colony formation of CML SPCs. Downstream of this, inhibition of E2F1 also reduced proliferation of CML SPCs, leading to p53-mediated apoptosis. In addition, we demonstrate that E2F1 plays a pivotal role in regulating CML SPC proliferation status. Thus, for the first time, we highlight the mechanism of hsa-mir183/EGR1–mediated E2F1 regulation and demonstrate this axis as a novel, critical factor for CML SPC survival, offering new insights into leukemic stem cell eradication.
  • Published In

  • Blood  Journal
  • Digital Object Identifier (doi)

    Author List

  • Pellicano F; Park L; Hopcroft LEM; Shah MM; Jackson L; Scott MT; Clarke CJ; Sinclair A; Abraham SA; Hair A
  • Start Page

  • 1532
  • End Page

  • 1544
  • Volume

  • 131
  • Issue

  • 14