The Chemokine CCL3 Regulates Myeloid Differentiation and Hematopoietic Stem Cell Numbers.

Abstract:

:The chemokine CCL3 is frequently overexpressed in malignancies and overexpression leads to microenvironmental dysfunction. In murine models of chronic myelogenous leukemia (CML), CCL3 is critical for the maintenance of a leukemia stem cell population, and leukemia progression. With CCL3 implicated as a potentially viable therapeutic target, it is important to carefully characterize its role in normal hematopoietic homeostasis. CCL3-/- mice were used to evaluate the role of CCL3 in regulating hematopoietic stem and progenitor cell (HSPC) populations. CCL3-/- mice had loss of mature myeloid populations, while myeloid progenitors and HSPCs were increased, and microenvironmental populations were unchanged. These data show that CCL3 promotes myeloid lineage differentiation and the size of the HSPC pool independent of the supportive bone marrow microenvironment. Our results demonstrate a previously unrecognized role of CCL3 in the maintenance of homeostatic hematopoiesis that should be evaluated when targeting CCL3 signaling for the treatment of hematologic malignancy.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Staversky RJ,Byun DK,Georger MA,Zaffuto BJ,Goodman A,Becker MW,Calvi LM,Frisch BJ

doi

10.1038/s41598-018-32978-y

subject

Has Abstract

pub_date

2018-10-02 00:00:00

pages

14691

issue

1

issn

2045-2322

pii

10.1038/s41598-018-32978-y

journal_volume

8

pub_type

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