ORCID Profile
0000-0001-5716-3212
Current Organisation
University of Veterinary Medicine Vienna
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Publisher: American Association for the Advancement of Science (AAAS)
Date: 25-06-2021
Abstract: Inflammation induces macrophage histone lactylation uncoupled from arginine metabolism or M2 polarization.
Publisher: Informa UK Limited
Date: 22-01-2015
Publisher: American Society of Hematology
Date: 09-10-2014
DOI: 10.1182/BLOOD-2014-03-564450
Abstract: Loss of STAT3 in NK cells enhances the expression of granzyme B, perforin, and DNAM-1, resulting in enhanced tumor surveillance. STAT3 binds the IFN-γ promoter and interferes with cytokine-induced IFN-γ production in NK cells.
Publisher: Springer Science and Business Media LLC
Date: 22-12-2013
DOI: 10.1038/NM.3424
Publisher: American Society of Hematology
Date: 16-08-2018
DOI: 10.1182/BLOOD-2017-10-810739
Abstract: Inhibition of Janus-kinase 1/2 (JAK1/2) is a mainstay to treat myeloproliferative neoplasms (MPN). Sporadic observations reported the co-incidence of B-cell non-Hodgkin lymphomas during treatment of MPN with JAK1/2 inhibitors. We assessed 626 patients with MPN, including 69 with myelofibrosis receiving JAK1/2 inhibitors for lymphoma development. B-cell lymphomas evolved in 4 (5.8%) of 69 patients receiving JAK1/2 inhibition compared with 2 (0.36%) of 557 with conventional treatment (16-fold increased risk). A similar 15-fold increase was observed in an independent cohort of 929 patients with MPN. Considering primary myelofibrosis only (N = 216), 3 lymphomas were observed in 31 inhibitor-treated patients (9.7%) vs 1 (0.54%) of 185 control patients. Lymphomas were of aggressive B-cell type, extranodal, or leukemic with high MYC expression in the absence of JAK2 V617F or other MPN-associated mutations. Median time from initiation of inhibitor therapy to lymphoma diagnosis was 25 months. Clonal immunoglobulin gene rearrangements were already detected in the bone marrow during myelofibrosis in 16.3% of patients. Lymphomas occurring during JAK1/2 inhibitor treatment were preceded by a preexisting B-cell clone in all 3 patients tested. Sequencing verified clonal identity in 2 patients. The effects of JAK1/2 inhibition were mirrored in Stat1−/− mice: 16 of 24 mice developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B cells. Transplantations of bone marrow from diseased mice unmasked the outgrowth of a malignant B-cell clone evolving into aggressive B-cell leukemia-lymphoma. We conclude that JAK/STAT1 pathway inhibition in myelofibrosis is associated with an elevated frequency of aggressive B-cell lymphomas. Detection of a preexisting B-cell clone may identify in iduals at risk.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2016
DOI: 10.1158/2159-8290.CD-15-0732
Abstract: Natural killer (NK) cells are tightly regulated by the JAK–STAT signaling pathway and cannot survive in the absence of STAT5. We now report that STAT5-deficient NK cells can be rescued by overexpression of BCL2. Our experiments define STAT5 as a master regulator of NK-cell proliferation and lytic functions. Although NK cells are generally responsible for killing tumor cells, the rescued STAT5-deficient NK cells promote tumor formation by producing enhanced levels of the angiogenic factor VEGFA. The importance of VEGFA produced by NK cells was verified by experiments with a conditional knockout of VEGFA in NK cells. We show that STAT5 normally represses the transcription of VEGFA in NK cells, in both mice and humans. These findings reveal that STAT5-directed therapies may have negative effects: In addition to impairing NK-cell–mediated tumor surveillance, they may even promote tumor growth by enhancing angiogenesis. Significance: The importance of the immune system in effective cancer treatment is widely recognized. We show that the new signal interceptors targeting the JAK–STAT5 pathway may have dangerous side effects that must be taken into account in clinical trials: inhibiting JAK–STAT5 has the potential to promote tumor growth by enhancing NK-cell–mediated angiogenesis. Cancer Discov 6(4) 414–29. ©2016 AACR. See related commentary by Ni and Cerwenka, p. 347. This article is highlighted in the In This Issue feature, p. 331
Publisher: Informa UK Limited
Date: 10-2012
DOI: 10.4161/ONCI.21284
No related grants have been discovered for Birgit Strobl.