Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Reduced Expression of Sprouty1 Contributes to the Aberrant Proliferation and Impaired Apoptosis of Acute Myeloid Leukemia Cells

Valentina Rosso
,
Crisitina Panuzzo
,
Jessica Petiti
ORCID logo ,
Sonia Carturan
,
Matteo Dragani
,
Giacomo Andreani
ORCID logo ,
Carmen Fava
,
Giuseppe Saglio
,
Enrico Bracco
ORCID logo ,
Daniela Cilloni
* ORCID logo
Version 1 : Received: 10 May 2019 / Approved: 13 May 2019 / Online: 13 May 2019 (08:23:54 CEST)

A peer-reviewed article of this Preprint also exists.

Rosso, V.; Panuzzo, C.; Petiti, J.; Carturan, S.; Dragani, M.; Andreani, G.; Fava, C.; Saglio, G.; Bracco, E.; Cilloni, D. Reduced Expression of Sprouty1 Contributes to the Aberrant Proliferation and Impaired Apoptosis of Acute Myeloid Leukemia Cells. J. Clin. Med. 2019, 8, 972. Rosso, V.; Panuzzo, C.; Petiti, J.; Carturan, S.; Dragani, M.; Andreani, G.; Fava, C.; Saglio, G.; Bracco, E.; Cilloni, D. Reduced Expression of Sprouty1 Contributes to the Aberrant Proliferation and Impaired Apoptosis of Acute Myeloid Leukemia Cells. J. Clin. Med. 2019, 8, 972.

Abstract

In most of acute myeloid leukemia patients there is an aberrant tyrosine kinases activity. The Sprouty family proteins were originally identified in Drosophila melanogaster as antagonists of Breathless, the mammalian ortholog of fibroblast growth factor receptor. This family proteins 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 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 acute myeloid leukemia. Furthermore, we found a correlation between Sprouty1 and FoxO3a delocalization in AML at diagnosis, suggesting a multistep regulation of RAF–MEK–ERK signaling in human cancers.

Keywords

Sprouty1; proliferation; tyrosine kinase

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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