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Exp Hematol. 2016 Jul;44(7):590-595.e1. doi: 10.1016/j.exphem.2016.04.001. Epub 2016 Apr 11.

GFI1(36N) as a therapeutic and prognostic marker for myelodysplastic syndrome.

Author information

1
Department of Hematology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
2
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland, OH, USA.
3
Department of Hematology and Oncology, University Hospital Düsseldorf, Düsseldorf, Germany.
4
Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
5
Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany.
6
Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany.
7
Lowy Cancer Research Centre and Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
8
Center for Hematology and Regenerative Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
9
Department of Molecular Medicine, University of Pavia, and Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
10
Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
11
Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
12
Medical Department with Focus on Hematology/Oncology Charite Berlin, Campus Virchow-Klinikum, Berlin, Germany.
13
Institut de Recherches Cliniques de Montréal (IRCM), Hematopoiesis and Cancer Research Unit, and Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Canada.
14
Department of Hematology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany. Electronic address: Cyrus.Khandanpour@uk-essen.de.

Abstract

Inherited gene variants play an important role in malignant diseases. The transcriptional repressor growth factor independence 1 (GFI1) regulates hematopoietic stem cell (HSC) self-renewal and differentiation. A single-nucleotide polymorphism of GFI1 (rs34631763) generates a protein with an asparagine (N) instead of a serine (S) at position 36 (GFI1(36N)) and has a prevalence of 3%-5% among Caucasians. Because GFI1 regulates myeloid development, we examined the role of GFI1(36N) on the course of MDS disease. To this end, we determined allele frequencies of GFI1(36N) in four independent MDS cohorts from the Netherlands and Belgium, Germany, the ICGC consortium, and the United States. The GFI1(36N) allele frequency in the 723 MDS patients genotyped ranged between 9% and 12%. GFI1(36N) was an independent adverse prognostic factor for overall survival, acute myeloid leukemia-free survival, and event-free survival in a univariate analysis. After adjustment for age, bone marrow blast percentage, IPSS score, mutational status, and cytogenetic findings, GFI1(36N) remained an independent adverse prognostic marker. GFI1(36S) homozygous patients exhibited a sustained response to treatment with hypomethylating agents, whereas GFI1(36N) patients had a poor sustained response to this therapy. Because allele status of GFI1(36N) is readily determined using basic molecular techniques, we propose inclusion of GFI1(36N) status in future prospective studies for MDS patients to better predict prognosis and guide therapeutic decisions.

PMID:
27080012
PMCID:
PMC4917888
DOI:
10.1016/j.exphem.2016.04.001
[Indexed for MEDLINE]
Free PMC Article

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