BoneKEy Reports | BoneKEy Watch

Role of the bone marrow microenvironment in CML and AML



DOI:10.1038/bonekey.2013.238

Altering niches within the bone marrow microenvironment (BMM) could be the key to reducing the viability of drug-resistant or persistent leukemia stem cells (LSCs) in acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML). To investigate how this might be possible, Krause et al. induced CML-like and AML-like leukemia in wild-type and transgenic mice, which expressed the receptor for parathyroid hormone (PTH) or PTH-related peptide specifically within the osteoblastic cell line.

Mortality of transgenic mice with induced CML was significantly lower than in wild-type mice, and overall survival was significantly longer. LSCs engrafted in the bone marrow of the transgenic recipients but did not survive in the long term. Transgenic mice experienced less severe disease because the number and longevity of LSCs were reduced and because the progenitor pool for leukemic cells in the BMM was reduced.

Similar experiments to induce AML produced contrasting findings – AML was more severe in the transgenic mice because of a greater number of clones of leukemic cells surviving in the BMM.

Editor’s comment: In this study, alteration of the BMM by osteoblast-specific PTH receptor activation caused attenuation in the BDR-ABL1-induced CML model but led to enhancement in the MLL-AF9-induced AML model in mice. These results demonstrate that CML and AML stem cell niches are distinct, and suggest that PTH may have therapeutic potential to control CML by altering the CML stem cell niche.


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