Journal article

Distinct effects of ruxolitinib and interferon-alpha on murine JAK2V617F myeloproliferative neoplasm hematopoietic stem cell populations

Rebecca J Austin, Jasmin Straube, Claudia Bruedigam, Gabor Pali, Sebastien Jacquelin, Therese Vu, Joanne Green, Julius Graesel, Lianne Lansink, Leanne Cooper, Shin-Jye Lee, Nien-Tsu Chen, Chung-Wei Lee, Ashraful Haque, Florian H Heidel, Richard D'Andrea, Geoff R Hill, Ann Mullally, Michael D Milsom, Megan Bywater Show all

LEUKEMIA | SPRINGERNATURE | Published : 2020

Abstract

JAK2V617F is the most common mutation in patients with BCR-ABL negative myeloproliferative neoplasms (MPNs). The eradication of JAK2V617F hematopoietic stem cells (HSCs) is critical for achieving molecular remissions and cure. We investigate the distinct effects of two therapies, ruxolitinib (JAK1/2 inhibitor) and interferon-alpha (IFN-α), on the disease-initiating HSC population. Whereas ruxolitinib inhibits Stat5 activation in erythroid progenitor populations, it fails to inhibit this same pathway in HSCs. In contrast, IFN-α has direct effects on HSCs. Furthermore, STAT1 phosphorylation and pathway activation is greater after IFN-α stimulation in Jak2V617F murine HSCs with increased induct..

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University of Melbourne Researchers