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.
Highlights
Acute myeloid leukaemia (AML) is a malignant myeloproliferative disease of the bone marrow accounting for ~10% of all haematological disorders[1, 2]
The distribution of Growth Factor Independence 1 (GFI1) expression amongst all acute myeloid leukaemia (AML) patients is not significantly different to that seen in the cytogenetically normal AML (CN-AML) subgroup (Fig. 1A)
We show that higher levels of GFI1 expression can be used to predict unfavourable outcome in AML patients with normal cytogenetics, and thereby provide a possible stratification for therapy choices
Summary
Acute myeloid leukaemia (AML) is a malignant myeloproliferative disease of the bone marrow accounting for ~10% of all haematological disorders[1, 2]. Associated with an increased predisposition towards AML led to the identification of a serine-asparagine substitution in the N-terminal region of GFI1 (GFI136N)[17] In line with these findings, Hönes et al analysed a cohort of 524 de novo AML cases and concluded that low expression of GFI1 is linked with an inferior prognosis[18]. In this study we have further analysed publicly available AML data with respect to the link between GFI1 expression and prognosis, but have stratified patients on the basis of the mutational status of their disease. This analysis has revealed that in cytogenetically normal AML (CN-AML) patients, high GFI1 expression predicts a significantly inferior overall survival. This higher GFI1 expression correlated with higher FLT3 levels and a gene expression profile reminiscent of that seen in AML with the FLT3-ITD mutation, suggesting an important molecular connection between these factors in CN-AML
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
