PMID- 9694728 OWN - NLM STAT- MEDLINE DCOM- 19980910 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 92 IP - 4 DP - 1998 Aug 15 TI - The kinetics and extent of engraftment of chronic myelogenous leukemia cells in non-obese diabetic/severe combined immunodeficiency mice reflect the phase of the donor's disease: an in vivo model of chronic myelogenous leukemia biology. PG - 1390-6 AB - In vitro studies have provided little consensus on the kinetic abnormality underlying the myeloid expansion of chronic myelogenous leukemia (CML). Transplantation of human CML cells into non-obese diabetic mice with severe immunodeficiency disease (NOD/SCID mice) may therefore be a useful model. A CML cell line (BV173) and peripheral blood cells collected from CML patients in chronic phase (CP), accelerated phase (AP), or blastic phase (BP) were injected into preirradiated NOD/SCID mice. Animals were killed at serial intervals; cell suspensions and/or tissue sections from different organs were studied by immunohistochemistry and/or flow cytometry using antihuman CD45 monoclonal antibodies (MoAbs), and by fluorescence in situ hybridization (FISH) for the BCR-ABL fusion gene. One hour after injection, cells were sequestered in the lungs and liver, but 2 weeks later they were no longer detectable in either site. Similar short-term kinetics were observed using 51Cr-labeled cells. The first signs of engraftment for BV173, AP, and BP cells were detected in the bone marrow (BM) at 4 weeks. At 8 weeks the median percentages of human cells in murine marrow were 4% (range, 1 to 9) for CP, 11% (range, 5 to 36) for AP, 38.5% (range, 18 to 79) for BP, and 54% (range, 31 to 69) for BV173. CP cells progressively infiltrated BM (21%) and spleen (6%) by 18 to 20 weeks; no animals injected with the cell line or BP cells survived beyond 12 weeks. The rate of increase in human cell numbers was higher for BP (7.3%/week) as compared with CP (0.9%/week) and AP (0. 5%/week). FISH analysis with BCR and ABL probes showed that some of the human cells engrafting after injection of CP cells lacked a BCR-ABL gene and were presumably normal. We conclude that CML cells proliferate in NOD/SCID mice with kinetics that recapitulate the phase of the donor's disease, thus providing an in vivo model of CML biology. CI - Copyright 1998 by The American Society of Hematology. FAU - Dazzi, F AU - Dazzi F AD - Department of Haematology, Imperial College School of Medicine at Hammersmith Hospital, London, UK. f.dazzi@rpms.ac.uk FAU - Capelli, D AU - Capelli D FAU - Hasserjian, R AU - Hasserjian R FAU - Cotter, F AU - Cotter F FAU - Corbo, M AU - Corbo M FAU - Poletti, A AU - Poletti A FAU - Chinswangwatanakul, W AU - Chinswangwatanakul W FAU - Goldman, J M AU - Goldman JM FAU - Gordon, M Y AU - Gordon MY LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Biomarkers, Tumor) RN - 0 (DNA, Neoplasm) RN - EC 2.7.10.2 (Fusion Proteins, bcr-abl) SB - IM MH - Animals MH - Biomarkers, Tumor/genetics MH - Blast Crisis/pathology MH - Bone Marrow/pathology MH - DNA, Neoplasm/genetics MH - Disease Progression MH - Fusion Proteins, bcr-abl/genetics MH - Graft Survival MH - Humans MH - In Situ Hybridization MH - Kinetics MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*pathology MH - Leukemia, Myeloid, Accelerated Phase/pathology MH - Leukemia, Myeloid, Chronic-Phase/pathology MH - Liver/pathology MH - Lung/pathology MH - Mice MH - Mice, Inbred NOD MH - Mice, SCID MH - Neoplasm Transplantation MH - Neoplastic Cells, Circulating MH - Neoplastic Stem Cells/pathology/*transplantation MH - Specific Pathogen-Free Organisms MH - Tissue Distribution MH - Transplantation, Heterologous EDAT- 1998/08/08 00:00 MHDA- 1998/08/08 00:01 CRDT- 1998/08/08 00:00 PHST- 1998/08/08 00:00 [pubmed] PHST- 1998/08/08 00:01 [medline] PHST- 1998/08/08 00:00 [entrez] AID - S0006-4971(20)55195-1 [pii] PST - ppublish SO - Blood. 1998 Aug 15;92(4):1390-6.