BCR-ABL-transformed GMP as myeloid leukemic stem cells
| Autor: | Scott A. Stuart, Irina C. Hunton, Yosuke Minami, Catriona Jamieson, Asoka Banno, Tomokatsu Ikawa, Cornelis Murre, Dennis J. Young, Tomoki Naoe, Yong Jiang, Jean Y. J. Wang |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Myeloid
Fusion Proteins bcr-abl Biology Granulocyte-Macrophage Progenitor Cells Models Biological Leukemogenic Mice hemic and lymphatic diseases Basic Helix-Loop-Helix Transcription Factors medicine Animals Progenitor cell Cells Cultured Myeloid Progenitor Cells beta Catenin Multidisciplinary Biological Sciences medicine.disease Mice Inbred C57BL Cell Transformation Neoplastic medicine.anatomical_structure Immunology Neoplastic Stem Cells Cancer research Stem cell Tyrosine kinase Ex vivo Chronic myelogenous leukemia |
| Zdroj: | Proceedings of the National Academy of Sciences. 105:17967-17972 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0808303105 |
| Popis: | During blast crisis of chronic myelogenous leukemia (CML), abnormal granulocyte macrophage progenitors (GMP) with nuclear β-catenin acquire self-renewal potential and may function as leukemic stem cells (Jamieson et al. N Engl J Med , 2004). To develop a mouse model for CML-initiating GMP, we expressed p210 BCR-ABL in an established line of E2A -knockout mouse BM cells that retain pluripotency in ex vivo culture. Expression of BCR-ABL in these cells reproducibly stimulated myeloid expansion in culture and generated leukemia-initiating cells specifically in the GMP compartment. The leukemogenic GMP displayed higher levels of β-catenin activity than either the nontransformed GMP or the transformed nonGMP, both in culture and in transplanted mouse BM. Although E2A -deficiency may have contributed to the formation of leukemogenic GMP, restoration of E2A-function did not reverse BCR-ABL-induced transformation. These results provide further evidence that BCR-ABL-transformed GMP with abnormal β-catenin activity can function as leukemic stem cells. |
| Databáze: | OpenAIRE |
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