We assessed parameters which affected homing and growth of human AML patient samples in NOD/SCID mice. We injected 25 AML samples from 19 different patients (in 6 patients, samples were obtained both at initial diagnosis and at relapse) both intravenously(IV) and intraperitoneally(IP) into NOD/SCID mice. Animals were sacrificed when they showed signs of leukemia or at 16 weeks after injection of AML cells. Mouse bone marrow and spleen were then analyzed for the presence of human AML cells, by flow cytometry. We found that 76% ( 19 of 25) of the AML samples had detectable (>1 %) AML cells in the bone marrows of transplanted mice, consistent with previously published results (Ailles, Blood 1999). In a comparison between routes of injection, we found that IV injected cells more efficiently generated human AML in NOD/SCID mice than did IP injections. We found no significant differences in leukemia development with AML samples obtained at initial diagnosis, as compared to samples obtained from the same patients at relapse. To address the question of whether CXCR4 expression might mediate homing of AML cells to the bone marrow, and thereby increase generation of AML in NOD/SCID mice, we assessed the expression of CXCR4 in 3 different AML patient samples (1 FABM1,1 M4,and l M5) prior to injection. In each sample, the majority of the leukemia cells expressed the CXCR4 membrane protein, by flow cytometry. However, only 2 of the 3 (the Ml and M4 samples) generated human AML in NOD/SCID mice. We attempted to increase AML cell expression of CXCR4 by culturing each of these 3 patient samples for 48 hours in medium containing stem cell factor(SCF) and IL-6, with or without Flt-3 ligand. Unlike normal progenitor cells, these AML cells did not have increased CXCR4 expression after culture under these conditions, nor did they generate higher levels of AML in NOD/SCID mice. We conclude that CXCR4 expression of AML cells appears neither to be regulated by SCF/IL-6/FU-3 ligand, nor to correlate, on a 1:1 basis, with development of human AML in NOD/SCID mice.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology