New therapeutic opportunities from dissecting the pre-B leukemia bone marrow microenvironment
© 2018 The Author(s) The microenvironments of leukemia and cancer are critical for multiple stages of malignancies, and they are an attractive therapeutic target. While skeletal abnormalities are commonly seen in children with acute lymphoblastic leukemia (ALL) prior to initiating osteotoxic therapy...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
2018
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| Online Access: | http://hdl.handle.net/20.500.11937/69138 |
| _version_ | 1848761977263882240 |
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| author | Cheung, Laurence Tickner, J. Hughes, A. Skut, P. Howlett, M. Foley, B. Oommen, J. Wells, J. He, B. Singh, S. Chua, G. Ford, J. Mullighan, C. Kotecha, R. Kees, U. |
| author_facet | Cheung, Laurence Tickner, J. Hughes, A. Skut, P. Howlett, M. Foley, B. Oommen, J. Wells, J. He, B. Singh, S. Chua, G. Ford, J. Mullighan, C. Kotecha, R. Kees, U. |
| author_sort | Cheung, Laurence |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2018 The Author(s) The microenvironments of leukemia and cancer are critical for multiple stages of malignancies, and they are an attractive therapeutic target. While skeletal abnormalities are commonly seen in children with acute lymphoblastic leukemia (ALL) prior to initiating osteotoxic therapy, little is known about the alterations to the bone marrow microenvironment during leukemogenesis. Therefore, in this study, we focused on the development of precursor-B cell ALL (pre-B ALL) in an immunocompetent BCR-ABL1+model. Here we show that hematopoiesis was perturbed, B lymphopoiesis was impaired, collagen production was reduced, and the number of osteoblastic cells was decreased in the bone marrow microenvironment. As previously found in children with ALL, the leukemia-bearing mice exhibited severe bone loss during leukemogenesis. Leukemia cells produced high levels of receptor activator of nuclear factor ?B ligand (RANKL), sufficient to cause osteoclast-mediated bone resorption. In vivo administration of zoledronic acid rescued leukemia-induced bone loss, reduced disease burden and prolonged survival in leukemia-bearing mice. Taken together, we provide evidence that targeting leukemia-induced bone loss is a therapeutic strategy for pre-B ALL. |
| first_indexed | 2025-11-14T10:40:14Z |
| format | Journal Article |
| id | curtin-20.500.11937-69138 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:40:14Z |
| publishDate | 2018 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-691382018-06-29T12:36:11Z New therapeutic opportunities from dissecting the pre-B leukemia bone marrow microenvironment Cheung, Laurence Tickner, J. Hughes, A. Skut, P. Howlett, M. Foley, B. Oommen, J. Wells, J. He, B. Singh, S. Chua, G. Ford, J. Mullighan, C. Kotecha, R. Kees, U. © 2018 The Author(s) The microenvironments of leukemia and cancer are critical for multiple stages of malignancies, and they are an attractive therapeutic target. While skeletal abnormalities are commonly seen in children with acute lymphoblastic leukemia (ALL) prior to initiating osteotoxic therapy, little is known about the alterations to the bone marrow microenvironment during leukemogenesis. Therefore, in this study, we focused on the development of precursor-B cell ALL (pre-B ALL) in an immunocompetent BCR-ABL1+model. Here we show that hematopoiesis was perturbed, B lymphopoiesis was impaired, collagen production was reduced, and the number of osteoblastic cells was decreased in the bone marrow microenvironment. As previously found in children with ALL, the leukemia-bearing mice exhibited severe bone loss during leukemogenesis. Leukemia cells produced high levels of receptor activator of nuclear factor ?B ligand (RANKL), sufficient to cause osteoclast-mediated bone resorption. In vivo administration of zoledronic acid rescued leukemia-induced bone loss, reduced disease burden and prolonged survival in leukemia-bearing mice. Taken together, we provide evidence that targeting leukemia-induced bone loss is a therapeutic strategy for pre-B ALL. 2018 Journal Article http://hdl.handle.net/20.500.11937/69138 10.1038/s41375-018-0144-7 restricted |
| spellingShingle | Cheung, Laurence Tickner, J. Hughes, A. Skut, P. Howlett, M. Foley, B. Oommen, J. Wells, J. He, B. Singh, S. Chua, G. Ford, J. Mullighan, C. Kotecha, R. Kees, U. New therapeutic opportunities from dissecting the pre-B leukemia bone marrow microenvironment |
| title | New therapeutic opportunities from dissecting the pre-B leukemia bone marrow microenvironment |
| title_full | New therapeutic opportunities from dissecting the pre-B leukemia bone marrow microenvironment |
| title_fullStr | New therapeutic opportunities from dissecting the pre-B leukemia bone marrow microenvironment |
| title_full_unstemmed | New therapeutic opportunities from dissecting the pre-B leukemia bone marrow microenvironment |
| title_short | New therapeutic opportunities from dissecting the pre-B leukemia bone marrow microenvironment |
| title_sort | new therapeutic opportunities from dissecting the pre-b leukemia bone marrow microenvironment |
| url | http://hdl.handle.net/20.500.11937/69138 |