Maintaining the self-renewal and differentiation potential of human CD34+ hematopoietic cells using a single genetic element

James C. Mulloy, Jorg Cammenga, Francisco J. Berguido, Kaida Wu, Ping Zhou, Raymond L. Comenzo, Suresh Jhanwar, Malcolm A.S. Moore, Stephen D. Nimer

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Hematopoiesis is a complex process involving hematopoietic stem cell (HSC) self-renewal and lineage commitment decisions that must continue throughout life. Establishing a reproducible technique that allows for the long-term ex vivo expansion of human HSCs and maintains self-renewal and multipotential differentiation will allow us to better understand these processes, and we report the ability of the leukemia-associated AML1-ETO fusion protein to establish such a system. AML1-ETO-transduced human CD34+ hematopoietic cells routinely proliferate in liquid culture for more than 7 months, remain cytokine dependent for survival and proliferation, and demonstrate self-renewal of immature cells that retain both lymphoid and myeloid potential in vitro. These cells continue to express the CD34 cell surface marker and have ongoing telomerase activity with maintenance of telomere ends, however they do not cause leukemia in nonobese diabetic-severe combined immunodeficiency (NOD/SCID) mice. Identification of the signaling pathways that are modulated by AML1-ETO and lead to the self-renewal of immature human progenitor cells may assist in identifying compounds that can efficiently expand human stem and progenitor cells ex vivo.

Original languageEnglish (US)
Pages (from-to)4369-4376
Number of pages8
JournalBlood
Volume102
Issue number13
DOIs
StatePublished - Dec 15 2003

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Mulloy, J. C., Cammenga, J., Berguido, F. J., Wu, K., Zhou, P., Comenzo, R. L., Jhanwar, S., Moore, M. A. S., & Nimer, S. D. (2003). Maintaining the self-renewal and differentiation potential of human CD34+ hematopoietic cells using a single genetic element. Blood, 102(13), 4369-4376. https://doi.org/10.1182/blood-2003-05-1762