Eradication of Acute Myeloid Leukemia with FLT3 Ligand-Targeted MiR-150 Nanoparticles

Overview

Journal Cancer Res

Specialty Oncology

Date 2016 Jun 10

PMID 27280396

Citations 32

Authors

Xi Jiang

Jason Bugno

Chao Hu

Yang Yang

Tobias Herold

Jun Qi

Ping Chen

Sandeep Gurbuxani

Stephen Arnovitz

Jennifer Strong

Kyle Ferchen

Bryan Ulrich

Hengyou Weng

Yungui Wang

Hao Huang

Shenglai Li

Mary Beth Neilly

Richard A Larson

Michelle M Le Beau

Stefan K Bohlander

Jie Jin

Zejuan Li

James E Bradner

Seungpyo Hong

Jianjun Chen

Affiliations

Soon will be listed here.

Abstract

Acute myeloid leukemia (AML) is a common and fatal form of hematopoietic malignancy. Overexpression and/or mutations of FLT3 have been shown to occur in the majority of cases of AML. Our analysis of a large-scale AML patient cohort (N = 562) indicates that FLT3 is particularly highly expressed in some subtypes of AML, such as AML with t(11q23)/MLL-rearrangements or FLT3-ITD. Such AML subtypes are known to be associated with unfavorable prognosis. To treat FLT3-overexpressing AML, we developed a novel targeted nanoparticle system: FLT3 ligand (FLT3L)-conjugated G7 poly(amidoamine) (PAMAM) nanosized dendriplex encapsulating miR-150, a pivotal tumor suppressor and negative regulator of FLT3 We show that the FLT3L-guided miR-150 nanoparticles selectively and efficiently target FLT3-overexpressing AML cells and significantly inhibit viability/growth and promote apoptosis of the AML cells. Our proof-of-concept animal model studies demonstrate that the FLT3L-guided miR-150 nanoparticles tend to concentrate in bone marrow, and significantly inhibit progression of FLT3-overexpressing AML in vivo, while exhibiting no obvious side effects on normal hematopoiesis. Collectively, we have developed a novel targeted therapeutic strategy, using FLT3L-guided miR-150-based nanoparticles, to treat FLT3-overexpressing AML with high efficacy and minimal side effects. Cancer Res; 76(15); 4470-80. ©2016 AACR.

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