A CELL INITIATING HUMAN ACUTE MYELOID-LEUKEMIA AFTER TRANSPLANTATION INTO SCID MICE

MOST human acute myeloid leukaemia (AML) cells have limited proliferat ive capacity, suggesting that the leukaemic clone may be maintained. b y a rare population of stem cells(1-5). This putative leukaemic stem c ell has not been characterized because the available in vitro assays c an only detect progenitors with limited proliferative and replating po tential(4-7). We have now identified an AML-initiating cell by transpl antation into severe combined immune-deficient (SCID) mice. These cell s homed to the bone marrow and proliferated extensively in response to in vivo cytokine treatment, resulting in a pattern of dissemination a nd leukaemic cell morphology similar to that seen in the original pati ents. Limiting dilution analysis showed that the frequency of these le ukaemia-initiating cells in the peripheral blood of AML patients was o ne 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 proper ties. This in vivo model replicates many aspects of human AML and defi nes a new leukaemia-initiating cell which is less mature than colony-f orming cells.