Suppressed apoptosis of pre-B cells in bone marrow of pre-leukemic p190bcr/abl transgenic mice
| Autor: | Q Yu, DG Osmond, J Brain, Laneuville P |
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| Rok vydání: | 2001 |
| Předmět: |
Cancer Research
Transgene Fusion Proteins bcr-abl Apoptosis Bone Marrow Cells Mice Transgenic Biology Mice hemic and lymphatic diseases medicine Animals Preleukemia Lymphopoiesis B-Lymphocytes ABL breakpoint cluster region Age Factors Hematology medicine.disease Hematopoietic Stem Cells Haematopoiesis Leukemia medicine.anatomical_structure Oncology Cancer research Bone marrow DNA Damage |
| Zdroj: | Leukemia. 15(5) |
| ISSN: | 0887-6924 |
| Popis: | Mice transgenic for a p190bcr/abl construct develop pre-B cell leukemia/lymphoma, providing a model of Ph+ ALL. To investigate events in tumorigenesis, immunofluorescence labeling, flow cytometry and a short-term culture assay were used to quantitate precursor B cells and their apoptotic rates in bone marrow of p190bcr/abl transgenic mice over a wide age range. Malignancies appeared rapidly at 8-12 weeks of age, followed by slower tumor onset. At 8-12 weeks in normal mice, the apoptotic rate fell among pro-B cells but increased steeply among pre-B cells, while the total number of B lineage cells declined. In contrast, in p190bcr/abl transgenic mice over the same time period, while pro-B cells remained normal in apoptotic rate and number, apoptosis of pre-B cells was markedly inhibited and the number of B lymphocytes increased. At later ages (14-30 weeks), B cell precursors in control mice remained constant in apoptotic activity and number, while in the few surviving transgenic mice B cell populations were expanded. The results reveal characteristic changes in apoptotic activity among B cell precursors in bone marrow during early life, severely perturbed in preleukemic p190bcr/abl transgenic mice by a preferential suppression of pre-B cell apoptosis. p190bcr/abl may thus promote leukemogenesis by permitting aberrant cells generated during early B cell development to evade a normal quality checkpoint and negative selection. |
| Databáze: | OpenAIRE |
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