Frontiers in Oncology (Oct 2021)

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

  • Cyrus Khandanpour,
  • Christine Eisfeld,
  • Subbaiah Chary Nimmagadda,
  • Marc S. Raab,
  • Niels Weinhold,
  • Anja Seckinger,
  • Dirk Hose,
  • Anna Jauch,
  • Asta Försti,
  • Asta Försti,
  • Asta Försti,
  • Kari Hemminki,
  • Kari Hemminki,
  • Thomas Hielscher,
  • Manuela Hummel,
  • Manuela Hummel,
  • Georg Lenz,
  • Hartmut Goldschmidt,
  • Hartmut Goldschmidt,
  • Stefanie Huhn

DOI
https://doi.org/10.3389/fonc.2021.757664
Journal volume & issue
Vol. 11

Abstract

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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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