Pharmacologic inhibition of PI3K p110d in mutant Shp2E76Kexpressing mice

Lisa Deng, Elizabeth L. Virts, Reuben Kapur, Rebecca Chan

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Juvenile myelomonocytic leukemia is a childhood malignancy that lacks effective chemotherapies and thus has poor patient outcomes. PI3K p110d 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.

Original languageEnglish (US)
Pages (from-to)84776-84781
Number of pages6
JournalOncotarget
Volume8
Issue number49
DOIs
StatePublished - Oct 17 2017

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Phosphatidylinositol 3-Kinases
Myeloid Cells
Juvenile Myelomonocytic Leukemia
Splenomegaly
B-Cell Chronic Lymphocytic Leukemia
Bone Marrow Cells
Blood Cells
Neoplasms
Stem Cells
Drug Therapy
Mutation
Therapeutics
Pharmaceutical Preparations

Keywords

  • In vivo
  • JMML
  • Mouse model
  • PI3K p110d
  • Shp2

ASJC Scopus subject areas

  • Oncology

Cite this

Pharmacologic inhibition of PI3K p110d in mutant Shp2E76Kexpressing mice. / Deng, Lisa; Virts, Elizabeth L.; Kapur, Reuben; Chan, Rebecca.

In: Oncotarget, Vol. 8, No. 49, 17.10.2017, p. 84776-84781.

Research output: Contribution to journalArticle

Deng, Lisa ; Virts, Elizabeth L. ; Kapur, Reuben ; Chan, Rebecca. / Pharmacologic inhibition of PI3K p110d in mutant Shp2E76Kexpressing mice. In: Oncotarget. 2017 ; Vol. 8, No. 49. pp. 84776-84781.
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