A STAT5B-CD9 axis determines self-renewal in hematopoietic and leukemic stem cells

Blood. 2021 Dec 9;138(23):2347-2359. doi: 10.1182/blood.2021010980.


The transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B are critical in hematopoiesis and leukemia. They are widely believed to have redundant functions, but we describe a unique role for STAT5B in driving the self-renewal of hematopoietic and leukemic stem cells (HSCs/LSCs). We find STAT5B to be specifically activated in HSCs and LSCs, where it induces many genes associated with quiescence and self-renewal, including the surface marker CD9. Levels of CD9 represent a prognostic marker for patients with STAT5-driven leukemia, and our findings suggest that anti-CD9 antibodies may be useful in their treatment to target and eliminate LSCs. We show that it is vital to consider STAT5A and STAT5B as distinct entities in normal and malignant hematopoiesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Self Renewal
  • Hematopoiesis
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology*
  • Humans
  • Leukemia / metabolism
  • Leukemia / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • STAT5 Transcription Factor / metabolism*
  • Signal Transduction*
  • Tetraspanin 29 / metabolism*
  • Tumor Cells, Cultured


  • STAT5 Transcription Factor
  • Tetraspanin 29