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

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.

• Authors: Tomohisa Baba, Yamato Tanabe, Soichiro Yoshikawa, Yoshinori Yamanishi, Soji Morishita, Norio Komatsu, Hajime Karasuyama, Atsushi Hirao, Naofumi Mukaida
• Journal: Blood (Blood) Vol. 127 Issue 21 Pg. 2607-17 (05 26 2016) ISSN: 1528-0020 [Electronic] United States
• PMID: 27006388 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 by The American Society of Hematology.

Chemical References

• CCL3 protein, human
• Ccl3 protein, mouse
• Chemokine CCL3
• Neoplasm Proteins

Topics

• Animals
• Basophils (metabolism, pathology)
• Bone Marrow (metabolism, pathology)
• Chemokine CCL3 (biosynthesis, genetics)
• Female
• Gene Expression Regulation, Leukemic
• Hematopoiesis
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (genetics, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Proteins (biosynthesis, genetics)
• Neoplastic Stem Cells (metabolism, pathology)