Towards a Better Understanding of Cohesin Mutations in AML
Cuartero, Sergi (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Innes, Andrew J (Faculty of Medicine. Centre for Haematology. Imperial College London)
Merkenschlager, M. (Imperial College London. Institute of Clinical Sciences)
Universitat Autònoma de Barcelona

Date:	2019
Abstract:	Classical driver mutations in acute myeloid leukemia (AML) typically affect regulators of cell proliferation, differentiation, and survival. The selective advantage of increased proliferation, improved survival, and reduced differentiation on leukemia progression is immediately obvious. Recent large-scale sequencing efforts have uncovered numerous novel AML-associated mutations. Interestingly, a substantial fraction of the most frequently mutated genes encode general regulators of transcription and chromatin state. Understanding the selective advantage conferred by these mutations remains a major challenge. A striking example are mutations in genes of the cohesin complex, a major regulator of three-dimensional genome organization. Several landmark studies have shown that cohesin mutations perturb the balance between self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPC). Emerging data now begin to uncover the molecular mechanisms that underpin this phenotype. Among these mechanisms is a role for cohesin in the control of inflammatory responses in HSPCs and myeloid cells. Inflammatory signals limit HSPC self-renewal and drive HSPC differentiation. Consistent with this, cohesin mutations promote resistance to inflammatory signals, and may provide a selective advantage for AML progression. In this review, we discuss recent progress in understanding cohesin mutations in AML, and speculate whether vulnerabilities associated with these mutations could be exploited therapeutically.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article de revisió ; Article ; Versió publicada
Subject:	AML ; Cohesin ; Hematopoiesis ; Inflammation ; Interferon ; Leukemia
Published in:	Frontiers in Oncology, Vol. 9 (september 2019) , p. 867, ISSN 2234-943X

DOI: 10.3389/fonc.2019.00867
PMID: 31552185

9 p, 1.3 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Published articles