Prevalence of the GFI1-36N SNP in multiple myeloma patients and its impact on the prognosis

Medientyp: E-Artikel

Titel: Prevalence of the GFI1-36N SNP in multiple myeloma patients and its impact on the prognosis

Beteiligte: Khandanpour, Cyrus [Verfasser:in]; Eisfeld, Christine [Verfasser:in]; Nimmagadda, Subbaiah Chary [Verfasser:in]; Raab, Marc-Steffen [Verfasser:in]; Weinhold, Niels [Verfasser:in]; Seckinger, Anja [Verfasser:in]; Hose, Dirk [Verfasser:in]; Jauch, Anna [Verfasser:in]; Försti, Asta [Verfasser:in]; Hemminki, Kari [Verfasser:in]; Hielscher, Thomas [Verfasser:in]; Hummel, Manuela [Verfasser:in]; Lenz, Georg [Verfasser:in]; Goldschmidt, Hartmut [Verfasser:in]; Huhn, Stefanie [Verfasser:in]

Erschienen: 25 October 2021

Sprache: Englisch

DOI: 10.3389/fonc.2021.757664

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Beschreibung: 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.

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