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Concise review: Getting to the core of inherited bone marrow failures

Lookup NU author(s): Dario Melguizo Sanchis, Dr Sujith Samarasinghe, Professor Lyle Armstrong, Professor Majlinda LakoORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Bone marrow failure syndromes (BMFS) are a group of disorders with complex pathophysiology characterized by a common phenotype of peripheral cytopenia and/or a hypoplastic bone marrow. Understanding genetic factors contributing to the pathophysiology of BMFS has enabled the identification of causative genes and development of diagnostic tests. To date more than 40 mutations in genes involved in maintenance of genomic stability, DNA repair, ribosome and telomere biology have been identified. In addition, pathophysiological studies have provided insights into several biological pathways leading to the characterization of genotype/phenotype correlations as well as the development of diagnostic approaches and management strategies. Recent developments in bone marrow transplant techniques and the choice of conditioning regimens have helped improve transplant outcomes. However, current morbidity and mortality remain unacceptable underlining the need for further research in this area. Studies in mice have largely been unable to mimic disease phenotype in humans due to difficulties in fully replicating the human mutations and the differences between mouse and human cells with regard to telomere length regulation, processing of reactive oxygen species and lifespan. Recent advances in induced pluripotency have provided novel insights into disease pathogenesis and have generated excellent platforms for identifying signaling pathways and functional mapping of haplo-insufficient genes involved in large-scale chromosomal deletions–associated disorders. In this review we have summarized the current state of knowledge in the field of BMFS with specific focus on modelling the inherited forms and how to best utilize these models for the development of targeted therapies.

Publication metadata

Author(s): Adam S, Melguzo Sanchis D, El-Kamah D, Samarasinghe S, Alharti S, Armstrong L, Lako M

Publication type: Review

Publication status: Published

Journal: Stem Cells

Year: 2017

Volume: 35

Issue: 2

Pages: 284-298

Print publication date: 01/02/2017

Online publication date: 04/12/2016

Acceptance date: 28/10/2016

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: AlphaMed Press


DOI: 10.1002/stem.2543