Neutral effect of Glioma-associated oncogene-1 expression on survival in myelofibrosis
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Wien Klin Wochenschr https://doi.org/10.1007/s00508-019-01572-1
Neutral effect of Glioma-associated oncogene-1 expression on survival in myelofibrosis Marko Lucijanic · Ana Livun · Katarina Marija Tupek · Tajana Stoos-Veic · Vlatko Pejsa · Zeljko Jonjic · Amina Fazlic Dzankic · Marija Ivic · Rajko Kusec
Received: 13 August 2019 / Accepted: 18 October 2019 © Springer-Verlag GmbH Austria, part of Springer Nature 2019
Summary This study retrospectively analyzed gliomaassociated oncogene 1 (GLI-1) mRNA expression in unfractionated bone marrow aspirates of 32 patients with myelofibrosis and 16 controls. It was found that GLI-1 expression did not significantly differ between primary, secondary myelofibrosis and controls (median difference in threshold cycles ΔCT 7.2, 7.3 and 6.9, respectively; P = 0.864), as well as that survival curves of myelofibrosis patients with higher/lower GLI-1 expression showed multiple overlaps and overall comparable course (P = 0.651). The results suggest that general upregulation of GLI-1 does not seem to be a feature of the disease and are in line with modest biological and clinical effects observed with inhibitors of Hedgehog signaling pathway in patients with myelofibrosis.
M. Lucijanic, MD PhD () · V. Pejsa · Z. Jonjic · M. Ivic · R. Kusec Hematology Department, University Hospital Dubrava, Av. Gojka Suska 6, 10000 Zagreb, Croatia [email protected] A. Livun · K. M. Tupek · R. Kusec Division of Molecular Diagnosis and Genetics, Clinical Department of Laboratory Diagnostics, University Hospital Dubrava, Zagreb, Croatia T. Stoos-Veic Department of Clinical Cytology and Cytometry, University Hospital Dubrava, Zagreb, Croatia Faculty of Medicine, University of Osijek, Osijek, Croatia V. Pejsa · R. Kusec School of Medicine, University of Zagreb, Zagreb, Croatia A. F. Dzankic Hematology Department, General Hospital Sisak, Sisak, Croatia
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Keywords Philadelphia negative myeloproliferative neoplasm · Bone marrow fibrosis · Sonic Hedgehog · Smoothened
Introduction The role of the Hedgehog signaling pathway is recognized in a number of fibrotic and malignant diseases [1]. Primary (PMF) and secondary myelofibrosis (SMF) are Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) characterized by clonal myeloproliferation and development of bone marrow (BM) fibrosis. Activation of Hedgehog signaling was reported to be present in murine BM transplant models of PMF [2] and increased expression of Hedgehog target genes was reported in granulocytes isolated from unselected MPN patients [2]. In addition, murine glioma-associated oncogene 1 (GLI-1) positive (effector of canonical Hedgehog signaling pathway) mesenchymal stromal cells (MSC) were reported to be recruited to support development of BM fibrosis, a process that seems to be responsive to specific GLI inhibition [3] and the same pathway might be active in humans [3]; however, therapeutic Hedgehog inhibition has so far shown only modest results in myelofibrosis [4, 5]. Also, inconsistent effects of such treatment on GLI-1 m
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