The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Differential regulation of myeloid leukemias by the bone marrow microenvironment
Open accessAbstract
Like their normal hematopoietic stem cell counterparts, leukemia stem cells (LSCs) in chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) are presumed to reside in specific niches in the bone marrow microenvironment (BMM) and may be the cause of relapse following chemotherapy. Targeting the niche is a new strategy to eliminate persistent and drug-resistant LSCs. CD44 (refs. 3,4) and interleukin-6 (ref. 5) have been implicated previously in the LSC niche. Transforming growth factor-β1 (TGF-β1) is released during bone remodeling and plays a part in maintenance of CML LSCs, but a role for TGF-β1 from the BMM has not been defined. Here, we show that alteration of the BMM by osteoblastic cell–specific activation of the parathyroid hormone (PTH) receptor attenuates BCR-ABL1 oncogene–induced CML-like myeloproliferative neoplasia (MPN) but enhances MLL-AF9 oncogene–induced AML in mouse transplantation models, possibly through opposing effects of increased TGF-β1 on the respective LSCs. PTH treatment caused a 15-fold decrease in LSCs in wild-type mice with CML-like MPN and reduced engraftment of immune-deficient mice with primary human CML cells. These results demonstrate that LSC niches in CML and AML are distinct and suggest that modulation of the BMM by PTH may be a feasible strategy to reduce LSCs, a prerequisite for the cure of CML.
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Cites
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“Parathyroid hormone stimulation of osteoblastic cells attenuates CML progression, but enhances acute myeloid leukemia (AML).(46) Another type of myeloproliferative neoplasms (MPN), polycythemia vera (PV), reduces nestin+ MSCs, and their rescue is associated with disease blockade.”
Background
Metadata
- Authors
- Krause, D. S., Fulzele, K., Catic, A., Sun, C. C., Dombkowski, D., Hurley, M. P., Lezeau, S., Attar, E., Wu, J. Y., Lin, H. Y., Divieti-Pajevic, P., Hasserjian, R. P., Schipani, E., Van Etten, R. A., & Scadden, D. T.
- Venue
- Nature Medicine
- Published
- 2013-10-27
- Volume
- 19
- Issue
- 11
- Pages
- 1513-1517
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2132053539
- Cited by
- 260
- References
- 6
- FWCI
- 19.62
- Type
- journal article
- Language
- en
- Open access
- green
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