title: Comparative long-term effects of interferon α and hydroxyurea on human hematopoietic progenitor cells.
abstract: Interferon α (IFNα) is used clinically to restore polyclonal hematopoiesis in patients with the myeloproliferative neoplasms polycythemia vera and essential thrombocythemia and to improve chemosensitivity in chronic myeloid leukemia patients. However, the mechanisms by which IFNα affects disease-initiating hematopoietic stem and progenitor cells (HSPCs) remain poorly understood. Although IFNα has been found to transiently impair quiescence of murine hematopoietic stem cells, its effects on human HSPCs have not been studied in vivo. Here, we compared bone marrow serially obtained from patients with myeloproliferative neoplasms before and during pegylated IFNα treatment against marrow serially obtained from patients on hydroxyurea. The percentage of HSPCs actively undergoing cell cycle was increased after pegylated IFNα treatment in a majority of patients compared with hydroxyurea-treated controls, suggesting that IFNα promotes cell division. Furthermore, transcriptional profiling revealed that cell cycle-associated genes were induced, whereas genes involved in HSPC quiescence were repressed during IFNα treatment. Compared with hydroxyurea-treated controls, pegylated IFNα-treated patients had similar numbers of HSPCs, but increased numbers of hematopoietic progenitors as determined by colony formation assay, indicating an increase in myeloid proliferation/differentiation. These effects occurred regardless of JAK2 mutational status. Together, these data provide the first in vivo evidence that pegylated IFNα promotes cell division and differentiation of human HSPCs.
authors.affiliation: Department of Pediatric Infectious Diseases, Baylor College of Medicine, Houston, Texas; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA. Electronic address: kyk@bcm.edu.
authors.forename: Katherine Y
authors.initials: KY
authors.lastname: King
authors.affiliation: Department of Pediatric Infectious Diseases, Baylor College of Medicine, Houston, Texas; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Katie A
authors.initials: KA
authors.lastname: Matatall
authors.affiliation: School of Medicine, Washington University, St. Louis, MO, USA.
authors.forename: Ching-Chieh
authors.initials: CC
authors.lastname: Shen
authors.affiliation: Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Goodell
authors.affiliation: Department of Hematology, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Sabina I
authors.initials: SI
authors.lastname: Swierczek
authors.affiliation: Department of Hematology, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
mesh_terms: D000368:Aged; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage*; D016898:Interferon-alpha / Q000008:administration & dosage*; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D011087:Polycythemia Vera / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013920:Thrombocythemia, Essential / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D016898:Interferon-alpha; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D006918:Hydroxyurea