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.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

King KY,Matatall KA,Shen CC,Goodell MA,Swierczek SI,Prchal JT

doi

10.1016/j.exphem.2015.05.013

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

912-918.e2

issue

10

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(15)00195-2

journal_volume

43

pub_type

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