A cell initiating human acute myeloid leukaemia after transplantation into SCID mice

Tsvee Lapidot, Christian Sirard, Josef Vormoor, Barbara Murdoch, Trang Hoang, Julio Caceres-Cortes, Mark Minden, Bruce Paterson, Michael A. Caligiuri, John E. Dick

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3885 Citaten (Scopus)

Samenvatting

MOST human acute myeloid leukaemia (AML) cells have limited proliferative capacity, suggesting that the leukaemic clone may be maintained by a rare population of stem cells1-5. This putative leukaemic stem cell has not been characterized because the available in vitro assays can only detect progenitors with limited proliferative and replating potential4-7. We have now identified an AML-initiating cell by transplantation into severe combined immune-deficient (SCID) mice. These cells homed to the bone marrow and proliferated extensively in response to in vivo cytokine treatment, resulting in a pattern of dissemination and leukaemic cell morphology similar to that seen in the original patients. Limiting dilution analysis showed that the frequency of these leukaemia-initiating cells in the peripheral blood of AML patients was one engraftment unit in 250,000 cells. We fractionated AML cells on the basis of cell-surface-marker expression and found that the leukaemia-initiating cells that could engraft SCID mice to produce large numbers of colony-forming progenitors were CD34+CD38-; however, the CD34 +CD38+ and CD34- fractions contained no cells with these properties. This in vivo model replicates many aspects of human AML and defines a new leukaemia-initiating cell which is less mature than colony-forming cells.

Originele taal-2Engels
Pagina's (van-tot)645-648
Aantal pagina's4
TijdschriftNature
Volume367
Nummer van het tijdschrift6464
DOI's
StatusGepubliceerd - 1994

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