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

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.DH was supported by Deutsche Forschungsgemeinschaft (SFB/TRR79) the German Federal Ministry of Education ("CLIOMMICS" (01ZX1309 and 01ZX1609) as well as "CAMPSIMM" (01ES1103)). KH is supported by the European Union's Horizon 2020 research and innovation programme, grant No 856620. CK is supported by the Jose Carreras Leukaemia Foundation (DJCLS 17R/2018), partially by the Deutsche Krebshilfe (70112392), Deutsche Forschungsgemeinschaft (KH331/2-3), and the intramural funding of the Faculty of Medicine at University Hospital of Muenster (Kha2/002/20)