Reduced proliferation of CD34(+) cells from patients with acute myeloid leukemia after gene transfer of INPP5D

Gene Therapy
A MetznerM Jücker

Abstract

Acute myeloid leukemia (AML) is a malignant disease characterized by deregulated proliferation of immature myeloid cells. Constitutive activation of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is frequently detected in approximately 50-70% of AML patients. The gene INPP5D encodes the SH2-containing inositol 5-phosphatase 1 (SHIP1), which is a negative regulator of PI3K/AKT signaling. After lentiviral-mediated gene transfer of INPP5D into CD34(+) cells derived from AML patients (n=12) the granulocyte macrophage-colony stimulating factor (GM-CSF)-dependent proliferation was reduced in all samples analyzed (average 86%; range 72-93%). An enzymatically inactive form of SHIP1 (D672A) had no effect. In addition, SHIP1 reduced the autonomous proliferation of CD34(+) cells from a patient with a secondary AML who had a very high peripheral blast count (300 x 10(9) l(-1)). These data show that SHIP1 can effectively block GM-CSF-dependent and autonomous proliferation of AML cells.

References

Apr 15, 2003·Reviews of Physiology, Biochemistry and Pharmacology·J KalesnikoffG Krystal
Dec 9, 2004·Expert Opinion on Therapeutic Targets·Linda S SteelmanJames A McCubrey

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Citations

Dec 3, 2009·Haematologica·Sophie ParkDidier Bouscary
May 16, 2014·Current Genetic Medicine Reports·Samantha L Rosenthal, M Ilyas Kamboh
Nov 9, 2010·Experimental Hematology·Melisa J HamiltonGerald Krystal
Sep 2, 2014·Oncology Reports·Hua XueJian-Min Luo
Jan 6, 2017·Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring·Eddie StageLiana G Apostolova

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