Prevalence of the GFI1-36N SNP in Multiple Myeloma Patients and Its Impact on the Prognosis.

Gfi1 SNP variant multiple myeloma prevalance prognosis

Journal

Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867

Informations de publication

Date de publication:
2021
Historique:
received: 12 08 2021
accepted: 01 10 2021
entrez: 11 11 2021
pubmed: 12 11 2021
medline: 12 11 2021
Statut: epublish

Résumé

Transcription factor Growth Factor Independence 1 (GFI1) regulates the expression of genes important for survival, proliferation and differentiation of hematopoietic cells. A single nucleotide polymorphism (SNP) variant of GFI1 (GFI1-36N: serine replaced by asparagine at position 36), has a prevalence of 5-7% among healthy Caucasians and 10-15% in patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) predisposing GFI-36N carriers to these diseases. Since GFI1 is implicated in B cell maturation and plasma cell (PC) development, we examined its prevalence in patients with multiple myeloma (MM), a haematological malignancy characterized by expansion of clonal PCs. Strikingly, as in MDS and AML, we found that the GFI1-36N had a higher prevalence among MM patients compared to the controls. In subgroup analyses, GFI1-36N correlates to a shorter overall survival of MM patients characterized by the presence of t(4;14) translocation and gain of 1q21 (≤3 copies). MM patients carrying gain of 1q21 (≥3 copies) demonstrated poor progression free survival. Furthermore, gene expression analysis implicated a role for GFI1-36N in epigenetic regulation and metabolism, potentially promoting the initiation and progression of MM.

Identifiants

pubmed: 34760702
doi: 10.3389/fonc.2021.757664
pmc: PMC8574071
doi:

Types de publication

Journal Article

Langues

eng

Pagination

757664

Informations de copyright

Copyright © 2021 Khandanpour, Eisfeld, Nimmagadda, Raab, Weinhold, Seckinger, Hose, Jauch, Försti, Hemminki, Hielscher, Hummel, Lenz, Goldschmidt and Huhn.

Déclaration de conflit d'intérêts

Author MH was employed by company Roche Diagnostics GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Cyrus Khandanpour (C)

Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany.

Christine Eisfeld (C)

Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany.

Subbaiah Chary Nimmagadda (SC)

Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany.

Marc S Raab (MS)

Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.

Niels Weinhold (N)

Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.

Anja Seckinger (A)

Department of Hematology and Immunology, Myeloma Center Brussels & Laboratory for Myeloma research, Vrije Universiteit Brussel (VUB), Jette, Belgium.

Dirk Hose (D)

Department of Hematology and Immunology, Myeloma Center Brussels & Laboratory for Myeloma research, Vrije Universiteit Brussel (VUB), Jette, Belgium.

Anna Jauch (A)

Institute of Human Genetics, University Heidelberg, Heidelberg, Germany.

Asta Försti (A)

Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Kari Hemminki (K)

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Pilsen, Czechia.

Thomas Hielscher (T)

Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Manuela Hummel (M)

Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Roche Diagnostics GmbH, Penzberg, Germany.

Georg Lenz (G)

Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany.

Hartmut Goldschmidt (H)

Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
National Centre of Tumor Diseases, Heidelberg, Germany.

Stefanie Huhn (S)

Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.

Classifications MeSH