Prognostic significance of high GFI1 expression in AML of normal karyotype and its association with a FLT3-ITD signature

Journal article

Abstract Growth Factor Independence 1 (GFI1) is a transcriptional repressor that plays a critical role during both myeloid and lymphoid haematopoietic lineage commitment. Several studies have demonstrated the involvement of GFI1 in haematological malignancies and have suggested that low expression of GFI1 is a negative indicator of disease progression for both myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). In this study, we have stratified AML patients into those defined as having a normal karyotype (CN-AML). Unlike the overall pattern in AML, those patients with CN-AML have a poorer survival rate when GFI1 expression is high. In this group, high GFI1 expression is paralleled by higher FLT3 expression, and, even when the FLT3 gene is not mutated, exhibit a FLT3-ITD signature of gene expression. Knock-down of GFI1 expression in the human AML Fujioka cell line led to a decrease in the level of FLT3 RNA and protein and to the down regulation of FLT3-ITD signature genes, thus linking two major prognostic indicators for AML

Authors: Volpe, G; Walton, DS; Grainger, DE; Ward, C; Cauchy, P

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Scientific Reports
• Volume: 7
• Issue: 1
• Pages: 11148-11148
• Publication date: 2017-09-05
• DOI: 10.1038/s41598-017-11718-8
• EISSN: 2045-2322
• ISSN: 2045-2322
• Language: English
• Keywords: Bone marrow; Chromosome; Stem cell; Karyotype; Biology; Gene signature; Haematopoiesis; Cancer research; Immunology; Genetics; Gene expression; Myelodysplastic syndromes; Myeloid; Gene