Maintaining the self-renewal and differentiation potential of human CD34+ hematopoietic cells using a single genetic element Journal Article
| Authors: | Mulloy, J. C.; Cammenga, J.; Berguido, F. J.; Wu, K.; Zhou, P.; Comenzo, R. L.; Jhanwar, S.; Moore, M. A. S.; Nimer, S. D. |
| Article Title: | Maintaining the self-renewal and differentiation potential of human CD34+ hematopoietic cells using a single genetic element |
| 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. © 2003 by The American Society of Hematology. |
| Keywords: | signal transduction; leukemia; human cell; nonhuman; flow cytometry; polymerase chain reaction; reproducibility of results; mouse; animals; mice; cells, cultured; cell division; cd34 antigen; animal model; cell differentiation; mice, scid; enzyme activity; telomerase; genetic transduction; transcription factors; transduction, genetic; recombinant fusion proteins; nucleotide sequence; oncogene proteins, fusion; retrovirus vector; hematopoietic cell; hematopoietic stem cells; cell culture techniques; hematopoietic stem cell; phagocytosis; mice, inbred nod; colony-forming units assay; antigens, cd34; scid mouse; core binding factor alpha 2 subunit; southern blotting; humans; human; priority journal; article |
| Journal Title: | Blood |
| Volume: | 102 |
| Issue: | 13 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2003-12-13 |
| Start Page: | 4369 |
| End Page: | 4376 |
| Language: | English |
| DOI: | 10.1182/blood-2003-05-1762 |
| PUBMED: | 12946995 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
