Targeting FLT3-ITD signaling mediates ceramide-dependent mitophagy and attenuates drug resistance in AML-Reference-Cited by-同舟云学术

Targeting FLT3-ITD signaling mediates ceramide-dependent mitophagy and attenuates drug resistance in AML

Published:2016-10-13 Issue:15 Volume:128 Page:1944-1958
ISSN:0006-4971
Container-title:Blood
language:en
Short-container-title:

Author:

Dany Mohammed¹²,Gencer Salih¹²,Nganga Rose¹²,Thomas Raquela J.¹²,Oleinik Natalia¹²,Baron Kyla D.¹²,Szulc Zdzislaw M.¹,Ruvolo Peter³,Kornblau Steven³,Andreeff Michael³,Ogretmen Besim¹²

Affiliation:

1. Department of Biochemistry and Molecular Biology and

2. Hollings Cancer Center, Medical University of South Carolina, Charleston, SC; and

3. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX

Abstract

Key Points FLT3-ITD mutations suppress ceramide generation, and FLT3-ITD inhibition mediates ceramide-dependent mitophagy, leading to AML cell death. Alteration of mitochondrial ceramide prevents mitophagy, resulting in resistance to FLT3-ITD inhibition which is attenuated by LCL-461.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Link

http://ashpublications.org/blood/article-pdf/128/15/1944/1395822/1944.pdf

Reference52 articles.

1. Toward individualized therapy in acute myeloid leukemia: a contemporary review.;Kadia;JAMA Oncol,2015

2. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412.;Stone;Blood,2005

3. Mechanism of constitutive activation of FLT3 with internal tandem duplication in the juxtamembrane domain.;Kiyoi;Oncogene,2002

4. Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways.;Mizuki;Blood,2000

5. AML-associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations.;Choudhary;Blood,2005

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