DIFFERENTIAL GROWTH-PATTERNS IN SCID MICE OF PATIENT-DERIVED CHRONIC MYELOGENOUS LEUKEMIAS

The development of an ia vivo model for the study of CML would be of s ignificant importance in studying its biological behavior and developi ng novel therapeutic strategies. We examined the ability of human leuk emic cells derived from patients in either chronic (CP), accelerated ( AP) or blast phase (BP) CML to grow and disseminate in CB17-SCID mice by subcutaneous (s.c.) inoculation without conditioning treatment or a dministration of cytokines, Additionally, samples derived from patient s with CP-CML were injected s.c. into CB17-SCID mice treated with anti -Asialo GM1 tan anti-NK cell antibody) and NOD-SCID mice (absent NK ce ll activity) to study the potential role of NK cell-mediated anti-leuk emic activity in preventing the propagation of CP-CML cells. We observ ed a significant differential growth pattern of CML cells in the mice such that BP-CML grew rapidly as s.c. tumors and disseminated, while A P-CML or CP-CML cells grew temporarily as small nodules that spontaneo usly regressed and did not disseminate. This differential growth patte rn suggests possible important biological differences. Furthermore, no significant difference in s.c. growth or dissemination of CP-CML samp les derived from newly diagnosed patients in untreated CB17-SCID mice and CB-17 SCID mice treated with Anti-Asialo GM1 and NOD-SCID mice occ urred, suggesting that factors other than NK cell anti-leukemic activi ty may be important.