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Novel GFI1B variant dysregulates oncogenic factors
significant upregulation of GFI1, BCL2L1, TGFBR3, MYC, GATA1, and GATA3 in cells from the patients' peripheral blood. These genes are also differentially expressed in HEK cells overexpressing p32 or p37, confirming that p32 con- trols their transcription. Considering that these oncogenes are involved in hematopoietic differentiation and are dys- regulated in various types of cancer, including hematologi- cal malignancies,27 it would be interesting to establish whether the GFI1B-associated bleeding disorder could be part of the nosological entity called “Inherited thrombocy- topenia-associated genes with predisposition to neo- plasms”.30
Increasing the detected number of individuals with GFI1B mutations and creating a registry of individuals with GFI1B variants, including a comprehensive medical and family history and regular follow-up, would be of funda- mental importance in defining whether there is any increased risk of developing such hematological malignan- cies. Therefore, an effort should be made to identify patients with this rare form of thrombocytopenia by evalu- ating the CD34 expression on platelets, a useful assay in
defining the pathogenicity of variants that would otherwise be considered of uncertain significance.
Disclosures
No conflicts of interest to disclose.
Contributions
MF, NP, MCMK, and RB performed research; CM, TG, and MS performed data analysis; FM, PN and AP collected clinical data; MF, SA, and RB designed the study and wrote the manu- script; VB performed blood cell studies. All contributors have read and approved the manuscript.
Acknowledgement
The authors would like to thank patients for their participation in this project and Prof. Gughi D.L. for the constructive discus- sions.
Funding
This study was supported by IRCCS “Burlo Garofolo” (Ricerca Corrente 01/2018) and AIRC Grant IG-21974.
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