INPP4B Overexpression is Associated with Poor Clinical Outcome and Therapy Resistance in Acute Myeloid Leukemia

Overview

Journal Leukemia

Specialties Hematology
Oncology

Date 2015 Mar 5

PMID 25736236

Citations 28

Authors

I Dzneladze

R He

J F Woolley

M H Son

M H Sharobim

S A Greenberg

M Gabra

C Langlois

A Rashid

A Hakem

N Ibrahimova

A Arruda

B Lowenberg

P J M Valk

M D Minden

L Salmena

Affiliations

Soon will be listed here.

Abstract

In this study, we investigated the role of inositol polyphosphate-4-phosphatase, type-II (INPP4B) in acute myeloid leukemia (AML). We observed that AML patients with high levels of INPP4B (INPP4B(high)) had poor response to induction therapy, shorter event-free survival and shorter overall survival. Multivariate analyses demonstrated that INPP4B(high) was an independent predictor of poor prognosis, significantly improving current predictive models, where it outperformed conventional biomarkers including FLT3-ITD and NPM1. Furthermore, INPP4B(high) effectively segregated relative risk in AML patients with normal cytogenetics. The role of INPP4B on the biology of leukemic cells was assessed in vitro. Overexpression of INPP4B in AML cell lines enhanced colony formation potential, recapitulated the chemotherapy resistance observed in AML patients and promoted proliferation in a phosphatase-dependent, and Akt-independent manner. These findings reveal that INPP4B(high) has an unexpected role consistent with oncogenesis in AML, in contrast to its previously reported tumor-suppressive role in epithelial cancers. Overall, we propose that INPP4B is a novel prognostic biomarker in AML that has potential to be translated into clinical practice both as a disease marker and therapeutic target.

Citing Articles

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Lai M, Mao Z, Tang D, Lan S, Yan R, Xiang Q Sichuan Da Xue Xue Bao Yi Xue Ban. 2024; 55(5):1186-1194.

PMID: 39507966 PMC: 11536254. DOI: 10.12182/20240960205.

INPP4B promotes PDAC aggressiveness via PIKfyve and TRPML-1-mediated lysosomal exocytosis.

Saffi G, To L, Kleine N, Melo C, Chen K, Genc G J Cell Biol. 2024; 223(11).

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Role of inositol polyphosphate-4-phosphatase type II in oncogenesis of digestive system tumors.

Han L, Chen S, Du S World J Gastrointest Oncol. 2023; 15(10):1706-1716.

PMID: 37969410 PMC: 10631434. DOI: 10.4251/wjgo.v15.i10.1706.

Single-cell RNA sequencing depicts metabolic changes in children with aplastic anemia.

Zhou Q, Huang L, Liu Y, Huang J, Wen L, Yang J Front Oncol. 2023; 13:1075408.

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Tumor Suppressor Role of INPP4B in Chemoresistant Retinoblastoma.

Miroschnikov N, Drager O, Van Meenen D, Metz K, Budeus B, Dunker N J Oncol. 2023; 2023:2270097.

PMID: 36993823 PMC: 10042642. DOI: 10.1155/2023/2270097.

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