The exodus subfamily of CC chemokines inhibits the proliferation of chronic myelogenous leukemia progenitors.
Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue and play important roles in disease processes. Among the biologic activities of chemokines is inhibition of proliferation of 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 cloned a subfamily of CC chemokines that share similar amino-terminal peptide sequences and a remarkable ability to chemoattract T cells. These chemokines, Exodus-1/LARC/MIP-3alpha, Exodus-2/SLC/6Ckine/TCA4, and Exodus-3/CKbeta11/MIP-3beta, were found to inhibit proliferation of normal human marrow progenitors. The study described here found that these chemokines also inhibited the proliferation of progenitors in every sample of marrow from patients with CML that was tested. This demonstration of consistent inhibition of CML progenitor proliferation makes the 3 Exodus chemokines unique among chemokines. (Blood. 2000;95:1506-1508)
Hromas
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Hematology/Oncology, Biochemistry/Molecular Biology, Microbiology/Immunology, and the Walther Oncology Center, Indiana University Medical Center, Indianapolis, Indiana 46202, USA. rhromas@iupui.edu
Cripe
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L
Hangoc
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Cooper
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Broxmeyer
H E
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D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology* / Q000503:physiopathology*; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine
C515460:CCL19 protein, human; C108355:CCL20 protein, human; C515478:CCL21 protein, human; C106311:CCR6 protein, human; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine