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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 prevalen...

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Detalles Bibliográficos
Autores principales: Khandanpour, Cyrus, Eisfeld, Christine, Nimmagadda, Subbaiah Chary, Raab, Marc S., Weinhold, Niels, Seckinger, Anja, Hose, Dirk, Jauch, Anna, Försti, Asta, Hemminki, Kari, Hielscher, Thomas, Hummel, Manuela, Lenz, Georg, Goldschmidt, Hartmut, Huhn, Stefanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8574071/
https://www.ncbi.nlm.nih.gov/pubmed/34760702
http://dx.doi.org/10.3389/fonc.2021.757664
Descripción
Sumario: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.