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.

Department of Hematology and Immunology Myeloma Center Brussels and Laboratory for Myeloma research Vrije Universiteit Brussel Jette Belgium

Department of Hematology Oncology and Rheumatology University Hospital Heidelberg Heidelberg Germany

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

Division of Biostatistics German Cancer Research Center Heidelberg Germany

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany

Division of Molecular Genetic Epidemiology German Cancer Research Center Heidelberg Germany

Division of Pediatric Neurooncology German Cancer Research Center Heidelberg Germany

Faculty of Medicine and Biomedical Center in Pilsen Charles University Prague Pilsen Czechia

Hopp Children's Cancer Center Heidelberg Germany

Institute of Human Genetics University Heidelberg Heidelberg Germany

National Centre of Tumor Diseases Heidelberg Germany

Roche Diagnostics GmbH Penzberg Germany

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