HIGH-LEVEL ENGRAFTMENT OF NOD SCID MICE BY PRIMITIVE NORMAL AND LEUKEMIC HEMATOPOIETIC-CELLS FROM PATIENTS WITH CHRONIC MYELOID-LEUKEMIA INCHRONIC PHASE/

We have previously shown that intravenously injected peripheral blood (PB) or bone marrow (BM) cells from newly diagnosed chronic myeloid le ukemia (CML) patients can engraft the BM of sublethally irradiated sev ere combined immunodeficient (SCID) mice. We now report engraftment re sults for chronic phase CML cells in nonobese diabetic (NOD)/SCID reci pients which show the superiority of this latter model. Transplantatio n of NOD/SCID mice with 7 to 10 x 10(7) patient PB or BM cells resulte d in the continuing presence of human cells in the BM of the mice for up to 7 months, and primitive human CD34(+) cells, including those det ectable as colony-forming cells (CFC), as long-term culture-initiating cells, or by their coexpression of Thy-1, were found in a higher prop ortion of the NOD/SCID recipients analyzed, and at higher levels than were seen previously in SCID recipients. The human CFC and total human cells present in the BM of the NOD/SCID mice transplanted with CML ce lls also contained higher proportions of leukemic cells than were obta ined in the SCID model, and NOD/SCID mice could be repopulated with tr ansplants of enriched CD34(+) cells from patients with CML. These resu lts suggest that the NOD/SCID mouse may allow greater engraftment and amplification of both normal and leukemic (Ph+) cells sufficient for t he quantitation and characterization of the normal and leukemic stem c ells present in patients with CML. In addition, this model should make practical the investigation of mechanisms underlying progression of t he disease and the development of more effective in vivo therapies. (C ) 1998 by The American Society of Hematology.