GFI136N as a therapeutic and prognostic marker for myelodysplastic syndrome

Lacramioara Botezatu, Lars C. Michel, Hideki Makishima, Thomas Schroeder, Ulrich Germing, Rainer Haas, Bert Van der Reijden, Anne E. Marneth, Saskia M. Bergevoet, Joop H. Jansen, Bartlomiej Przychodzen, Marcin Wlodarski, Charlotte Niemeyer, Uwe Platzbecker, Gerhard Ehninger, Ashwin Unnikrishnan, Dominik Beck, John Pimanda, Eva Hellström-Lindberg, Luca MalcovatiJacqueline Boultwood, Andrea Pellagatti, Elli Papaemmanuil, Philipp Le Coutre, Jaspal Kaeda, Bertram Opalka, Tarik Möröy, Ulrich Dührsen, Jaroslaw Maciejewski, Cyrus Khandanpour

Research output: Contribution to journalArticle

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 (GFI136N) and has a prevalence of 3%-5% among Caucasians. Because GFI1 regulates myeloid development, we examined the role of GFI136N on the course of MDS disease. To this end, we determined allele frequencies of GFI136N in four independent MDS cohorts from the Netherlands and Belgium, Germany, the ICGC consortium, and the United States. The GFI136N allele frequency in the 723 MDS patients genotyped ranged between 9% and 12%. GFI136N 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, GFI136N remained an independent adverse prognostic marker. GFI136S homozygous patients exhibited a sustained response to treatment with hypomethylating agents, whereas GFI136N patients had a poor sustained response to this therapy. Because allele status of GFI136N is readily determined using basic molecular techniques, we propose inclusion of GFI136N status in future prospective studies for MDS patients to better predict prognosis and guide therapeutic decisions.

Original languageEnglish
Pages (from-to)590-595.e1
JournalExperimental Hematology
Volume44
Issue number7
DOIs
Publication statusPublished - Jul 1 2016

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Myelodysplastic Syndromes
Intercellular Signaling Peptides and Proteins
Gene Frequency
Asparagine
Belgium
Therapeutics
Hematopoietic Stem Cells
Acute Myeloid Leukemia
Cytogenetics
Netherlands
Serine
Disease-Free Survival
Single Nucleotide Polymorphism
Germany
Bone Marrow
Alleles
Prospective Studies
Survival
Genes
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Hematology

Cite this

Botezatu, L., Michel, L. C., Makishima, H., Schroeder, T., Germing, U., Haas, R., ... Khandanpour, C. (2016). GFI136N as a therapeutic and prognostic marker for myelodysplastic syndrome. Experimental Hematology, 44(7), 590-595.e1. https://doi.org/10.1016/j.exphem.2016.04.001

GFI136N as a therapeutic and prognostic marker for myelodysplastic syndrome. / Botezatu, Lacramioara; Michel, Lars C.; Makishima, Hideki; Schroeder, Thomas; Germing, Ulrich; Haas, Rainer; Van der Reijden, Bert; Marneth, Anne E.; Bergevoet, Saskia M.; Jansen, Joop H.; Przychodzen, Bartlomiej; Wlodarski, Marcin; Niemeyer, Charlotte; Platzbecker, Uwe; Ehninger, Gerhard; Unnikrishnan, Ashwin; Beck, Dominik; Pimanda, John; Hellström-Lindberg, Eva; Malcovati, Luca; Boultwood, Jacqueline; Pellagatti, Andrea; Papaemmanuil, Elli; Le Coutre, Philipp; Kaeda, Jaspal; Opalka, Bertram; Möröy, Tarik; Dührsen, Ulrich; Maciejewski, Jaroslaw; Khandanpour, Cyrus.

In: Experimental Hematology, Vol. 44, No. 7, 01.07.2016, p. 590-595.e1.

Research output: Contribution to journalArticle

Botezatu, L, Michel, LC, Makishima, H, Schroeder, T, Germing, U, Haas, R, Van der Reijden, B, Marneth, AE, Bergevoet, SM, Jansen, JH, Przychodzen, B, Wlodarski, M, Niemeyer, C, Platzbecker, U, Ehninger, G, Unnikrishnan, A, Beck, D, Pimanda, J, Hellström-Lindberg, E, Malcovati, L, Boultwood, J, Pellagatti, A, Papaemmanuil, E, Le Coutre, P, Kaeda, J, Opalka, B, Möröy, T, Dührsen, U, Maciejewski, J & Khandanpour, C 2016, 'GFI136N as a therapeutic and prognostic marker for myelodysplastic syndrome', Experimental Hematology, vol. 44, no. 7, pp. 590-595.e1. https://doi.org/10.1016/j.exphem.2016.04.001
Botezatu L, Michel LC, Makishima H, Schroeder T, Germing U, Haas R et al. GFI136N as a therapeutic and prognostic marker for myelodysplastic syndrome. Experimental Hematology. 2016 Jul 1;44(7):590-595.e1. https://doi.org/10.1016/j.exphem.2016.04.001
Botezatu, Lacramioara ; Michel, Lars C. ; Makishima, Hideki ; Schroeder, Thomas ; Germing, Ulrich ; Haas, Rainer ; Van der Reijden, Bert ; Marneth, Anne E. ; Bergevoet, Saskia M. ; Jansen, Joop H. ; Przychodzen, Bartlomiej ; Wlodarski, Marcin ; Niemeyer, Charlotte ; Platzbecker, Uwe ; Ehninger, Gerhard ; Unnikrishnan, Ashwin ; Beck, Dominik ; Pimanda, John ; Hellström-Lindberg, Eva ; Malcovati, Luca ; Boultwood, Jacqueline ; Pellagatti, Andrea ; Papaemmanuil, Elli ; Le Coutre, Philipp ; Kaeda, Jaspal ; Opalka, Bertram ; Möröy, Tarik ; Dührsen, Ulrich ; Maciejewski, Jaroslaw ; Khandanpour, Cyrus. / GFI136N as a therapeutic and prognostic marker for myelodysplastic syndrome. In: Experimental Hematology. 2016 ; Vol. 44, No. 7. pp. 590-595.e1.
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AU - Papaemmanuil, Elli

AU - Le Coutre, Philipp

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