Abstract
In most of the acute myeloid leukemia patients there is an aberrant tyrosine kinase activity. The prototype of Sprouty proteins was originally identified in Drosophila melanogaster as antagonists of Breathless, the mammalian ortholog of fibroblast growth factor receptor. Usually, SPRY family members are inhibitors of RAS signaling induced by tyrosine kinases receptors and they are implicated in negative feedback processes regulating several intracellular pathways. The present study aims to investigate the role of a member of the Sprouty family, Sprouty1, as a regulator of cell proliferation and growth in patients affected by acute myeloid leukemia. Sprouty1 mRNA and protein were both significantly down-regulated in acute myeloid leukemia cells compared to the normal counterpart, but they were restored when remission is achieved after chemotherapy. Ectopic expression of Sprouty1 revealed that it plays a key role in the proliferation and apoptotic defect that represent a landmark of the leukemic cells. Our study identified Sprouty1 as negative regulator involved in the aberrant signals of adult acute myeloid leukemia. Furthermore, we found a correlation between Sprouty1 and FoxO3a delocalization in acute myeloid leukemia (AML) patients at diagnosis, suggesting a multistep regulation of RAS signaling in human cancers.
Highlights
Acute myeloid leukemia (AML) develops from the malignant transformation of immature hematopoietic cells through a complex multistep process that requires the cooperation of different genetic alterations [1]
We investigated the role of Sprouty1 as the regulator of cell proliferation and growth in adult patients affected by acute myeloid leukemia (AML) and we studied the correlation between low Sprouty1 expression and FoxO3a delocalization in AML at diagnosis, suggesting a multistep regulation of RAS signaling in human cancers
We initially analyzed the Sprouty1 gene expression by quantitative Real-Time PCR in bone marrow (BM) and PB samples collected from 90 AML patients at diagnosis and 34 healthy subjects
Summary
Acute myeloid leukemia (AML) develops from the malignant transformation of immature hematopoietic cells through a complex multistep process that requires the cooperation of different genetic alterations [1]. In most of the AML patients, there is an aberrant tyrosine kinase (TK) activity, which results in an impaired differentiation, altered cell growth, and apoptosis defect. Sprouty proteins inhibit the RAS pathway, frequently constitutively active in many human tumors, contributing robustly to cells aggressiveness and invasiveness [2,3,4,5]. The Sprouty family proteins were initially identified in Drosophila melanogaster as antagonists of receptor tyrosine kinase (RTK) signaling during different morphogenetic processes, including the development of the trachea, the eye, the wing, and other tissues [6,7,8,9,10,11]. Sprouty proteins have been implicated in the regulation of the biological processes responsible for tumor growth, development, and metastasis, including cell proliferation, migration, invasion, and survival. The downregulation of Sprouty family members has been detected in a number of solid cancers such as breast, prostate, and renal cell carcinoma [3], as well as in leukemia [14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 call
