@article{0fcfc2745232492e84b256fc9f56c7f0,
title = "Dissecting chronic lymphocytic leukemia microenvironment signals in patients with unmutated disease: MicroRNA-22 regulates phosphatase and tensin homolog/AKT/FOXO1 pathway in proliferative leukemic cells",
abstract = "Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of clonal B cells arrested in G0/G1 stages that coexist with proliferative B cells. We identified one of these proliferative subsets in the peripheral blood from patients with unmutated disease (UM). Aiming to characterize the molecular mechanism underlying this proliferative behavior, we performed gene expression analysis of the mRNA and microRNAs in this leukemic subpopulation and compared results with those for the quiescent counterpart. Our results suggest that proliferation of this subset mainly depends on microRNA-22 overexpression, which induces phosphatase and tensin homolog (PTEN) down-regulation and phosphoinositide 3-kinase (PI3K)/AKT pathway activation. These results underline the role of the PI3K/AKT pathway at the origin of this proliferative pool in patients with UM CLL and provide additional rationale for the use of PI3K inhibitors.",
keywords = "CLL microenvironment signals, Unmutated patients",
author = "Florencia Palacios and Daniel Prieto and Cecilia Abreu and Santiago Ruiz and Pablo Morande and Tamara Fern{\'a}ndez-Calero and Gabriela Libisch and Landoni, {Ana In{\'e}s} and Pablo Oppezzo",
note = "Funding Information: This work was supported by grants from ANII: Fondo Clem-ente Estable (FCE-7273) and Fondo Maria Vi{\~n}as (FMV-7323). This work was partially funded by FOCEM (MERCOSUR Structural Convergence Fund), COF 03/11 and CYTED Program. We wish to thank Dr. Alfonso Cayota for his help with miR technologies, the Cell Biology Unit of the Institut Pasteur de Montevideo for their technical assistance in cell sorting analysis and Mrs. Ivana Faccini for her helpful assistance with manuscript correction. We also thank the patients with CLL for their cooperation and help in providing invaluable blood samples for this work. Publisher Copyright: {\textcopyright} 2015 Informa UK, Ltd.",
year = "2015",
month = may,
day = "1",
doi = "10.3109/10428194.2014.990900",
language = "English",
volume = "56",
pages = "1560--1565",
journal = "Leukemia and Lymphoma",
issn = "1042-8194",
publisher = "Informa Healthcare",
number = "5",
}