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Blood. 2016 May 26;127(21):2607-17. doi: 10.1182/blood-2015-10-673087. Epub 2016 Mar 22.

MIP-1α/CCL3-expressing basophil-lineage cells drive the leukemic hematopoiesis of chronic myeloid leukemia in mice.

Author information

1
Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan;
2
Department of Immune Regulation, Tokyo Medical and Dental University, Tokyo, Japan;
3
Department of Transfusion Medicine and Stem Cell Regulation and.
4
Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan; and.
5
Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.

Abstract

Basophilia is a frequently observed hematological abnormality in chronic myeloid leukemia (CML), but its pathophysiological roles are undefined. We previously demonstrated that an inflammatory chemokine, CCL3, preferentially acts on normal hematopoietic stem/progenitor cells and crucially contributes to the maintenance of leukemia initiating cells (LICs) in bone marrow (BM) during the initiation process of CML. However, the major cellular source of CCL3 in BM and the precise mechanism of CCL3-mediated maintenance of LICs remain to be investigated. To delineate the cellular process facilitating this CCL3-mediated crosstalk between normal and leukemic hematopoiesis, we precisely examined CCL3-expressing cells and their functions in both normal hematopoiesis and CML leukemogenesis. Herein, we demonstrate that basophils can constitutively express CCL3 to negatively regulate the normal hematopoietic process, especially hematopoietic reconstitution after BM transplantation. Moreover, CCL3-expressing basophil-like leukemia cells were found to accumulate in CML BM and supported the predominant expansion of LICs therein. These observations suggest that intra-BM basophil expansion can favor leukemia-tropic hematopoiesis in CML by providing CCL3, a potent inhibitor of normal hematopoiesis and that basophil-derived CCL3 may be a novel target molecule for the treatment of CML.

PMID:
27006388
DOI:
10.1182/blood-2015-10-673087
[Indexed for MEDLINE]
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