Acute Myeloid Leukaemia Disrupts Endogenous Myelo-erythropoiesis by Compromising the Adipocyte Bone Marrow Niche

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2017 Oct 17

PMID 29035359

Citations 107

Authors

Allison L Boyd

Jennifer C Reid

Kyle R Salci

Lili Aslostovar

Yannick D Benoit

Zoya Shapovalova

Mio Nakanishi

Deanna P Porras

Mohammed Almakadi

Clinton J V Campbell

Michael F Jackson

Catherine A Ross

Ronan Foley

Brian Leber

David S Allan

Mitchell Sabloff

Anargyros Xenocostas

Tony J Collins

Mickie Bhatia

Affiliations

Soon will be listed here.

Abstract

Acute myeloid leukaemia (AML) is distinguished by the generation of dysfunctional leukaemic blasts, and patients characteristically suffer from fatal infections and anaemia due to insufficient normal myelo-erythropoiesis. Direct physical crowding of bone marrow (BM) by accumulating leukaemic cells does not fully account for this haematopoietic failure. Here, analyses from AML patients were applied to both in vitro co-culture platforms and in vivo xenograft modelling, revealing that human AML disease specifically disrupts the adipocytic niche in BM. Leukaemic suppression of BM adipocytes led to imbalanced regulation of endogenous haematopoietic stem and progenitor cells, resulting in impaired myelo-erythroid maturation. In vivo administration of PPARγ agonists induced BM adipogenesis, which rescued healthy haematopoietic maturation while repressing leukaemic growth. Our study identifies a previously unappreciated axis between BM adipogenesis and normal myelo-erythroid maturation that is therapeutically accessible to improve symptoms of BM failure in AML via non-cell autonomous targeting of the niche.

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