The Exodus subfamily of CC chemokines inhibits the proliferation of chronic myelogenous leukemia progenitors

Chemokines are a family of related proteins that regulate leukocyte infiltr ation into inflamed tissue and play important roles in disease processes. A mong the biologic activities of chemokines is inhibition of proliferation o f normal hematopoietic progenitors. However, chemokines that inhibit normal progenitors rarely inhibit proliferation of hematopoietic progenitors from patients with chronic myelogenous leukemia (CML). We and others recently c loned a subfamily of CC chemokines that share similar aminoterminal peptide sequences and a remarkable ability to chemoattract T cells. These chemokin es, Exodus-1/LARC/MIP-3 alpha, Exodus-2/SLC/6Ckine/TCA4, and Exodus-3/CK be ta 11/MIP-3 beta, were found to inhibit proliferation of normal human marro w progenitors. The study described here found that these chemokines also in hibited the proliferation of progenitors in every sample of marrow from pat ients with CML that was tested. This demonstration of consistent inhibition of CML progenitor proliferation makes the 3 Exodus chemokines unique among chemokines. (C) 2000 by The American Society ct Hematology.