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Genetic hierarchy and temporal variegation in the clonal history of acute myeloid leukaemia
- Source :
- Nature Communications, Nature Communications, Nature Publishing Group, 2016, pp.12475. ⟨10.1038/ncomms12475⟩, Nature Communications, Vol 7, Iss 1, Pp 1-13 (2016), Nature Communications, 2016, 7, pp.12475. ⟨10.1038/ncomms12475⟩
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- In acute myeloid leukaemia (AML) initiating pre-leukaemic lesions can be identified through three major hallmarks: their early occurrence in the clone, their persistence at relapse and their ability to initiate multilineage haematopoietic repopulation and leukaemia in vivo. Here we analyse the clonal composition of a series of AML through these characteristics. We find that not only DNMT3A mutations, but also TET2, ASXL1 mutations, core-binding factor and MLL translocations, as well as del(20q) mostly fulfil these criteria. When not eradicated by AML treatments, pre-leukaemic cells with these lesions can re-initiate the leukaemic process at various stages until relapse, with a time-dependent increase in clonal variegation. Based on the nature, order and association of lesions, we delineate recurrent genetic hierarchies of AML. Our data indicate that first lesions, variegation and treatment selection pressure govern the expansion and adaptive behaviour of the malignant clone, shaping AML in a time-dependent manner.<br />Pre-leukaemic clones, together with the propensity to cause disease in mice, are characterized by appearing early in myeloid leukaemia and being found at relapse. Here, the authors identify clones in human samples and find that they are characterized by hierarchically organized genetic lesions, which can be used to track evolution of the disease.
- Subjects :
- 0301 basic medicine
Time Factors
Myeloid
Science
Clone (cell biology)
General Physics and Astronomy
Biology
medicine.disease_cause
Somatic evolution in cancer
Article
General Biochemistry, Genetics and Molecular Biology
Epigenesis, Genetic
Clonal Evolution
Mice
03 medical and health sciences
hemic and lymphatic diseases
medicine
Animals
Humans
neoplasms
Variegation
Gene Rearrangement
[SDV.GEN]Life Sciences [q-bio]/Genetics
Mutation
Multidisciplinary
Base Sequence
General Chemistry
Gene rearrangement
medicine.disease
Clone Cells
Hematopoiesis
Leukemia, Myeloid, Acute
Leukemia
Haematopoiesis
030104 developmental biology
medicine.anatomical_structure
Immunology
Single-Cell Analysis
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....a2957c610d80a444affe3137ac192aba