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
| Autor: | Margherita Corbo, Debora Capelli, Alessandro Poletti, John M. Goldman, Robert P. Hasserjian, Wimol Chinswangwatanakul, Finbarr Cotter, Myrtle Y. Gordon, Francesco Dazzi |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Severe combined immunodeficiency
Pathology medicine.medical_specialty Myeloid ABL Immunology Cell Biology Hematology Blastic Phase Biology medicine.disease Biochemistry Molecular biology Transplantation Myelogenous medicine.anatomical_structure hemic and lymphatic diseases medicine Bone marrow Chronic myelogenous leukemia |
| Zdroj: | Blood. 92:1390-1396 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v92.4.1390 |
| Popis: | 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 using51Cr-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. © 1998 by The American Society of Hematology. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|