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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.

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