Pharmacologic inhibition of PI3K p110δ in mutant Shp2E76K-expressing mice

Date

2017-10-03
Language
American English

Embargo Lift Date

Committee Members

Degree

Degree Year

Department

Grantor

Journal Title

Journal ISSN

Volume Title

Found At

Impact Journals

Abstract

Juvenile myelomonocytic leukemia is a childhood malignancy that lacks effective chemotherapies and thus has poor patient outcomes. PI3K p110δ has been found to promote hyperproliferation of cells expressing mutant Shp2. In this study, we tested the efficacy of a PI3Kδ inhibitor in mice expressing the Shp2 gain-of-function mutation, E76K. We found that in vivo treatment of mice led to significantly decreased splenomegaly, reduced frequency of bone marrow progenitor cells, and increased terminally differentiated peripheral blood myeloid cells. The survival of drug-treated mice was significantly prolonged compared to vehicle-treated controls, although mice from both groups ultimately succumbed to a similar myeloid cell expansion. PI3Kδ inhibitors are currently used to treat patients with relapsed lymphoid malignancies, such as chronic lymphocytic leukemia. The current findings provide evidence for using PI3Kδ inhibitors as a treatment strategy for JMML and potentially other myeloid diseases.

Description

item.page.description.tableofcontents

item.page.relation.haspart

Cite As

Deng, L., Virts, E. L., Kapur, R., & Chan, R. J. (2017). Pharmacologic inhibition of PI3K p110δ in mutant Shp2E76K-expressing mice. Oncotarget, 8(49), 84776–84781. https://doi.org/10.18632/oncotarget.21455

ISSN

1949-2553

Publisher

Series/Report

Sponsorship

Major

Extent

Identifier

Relation

Journal

Oncotarget

Source

PMC

Alternative Title

Type

Article

Number

Volume

Conference Dates

Conference Host

Conference Location

Conference Name

Conference Panel

Conference Secretariat Location

Version

Final published version

Full Text Available at

This item is under embargo {{howLong}}