Single cell analysis of clonal architecture in acute myeloid leukaemia.
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Embargo End Date
ICR Authors
Authors
Potter, N
Miraki-Moud, F
Ermini, L
Titley, I
Vijayaraghavan, G
Papaemmanuil, E
Campbell, P
Gribben, J
Taussig, D
Greaves, M
Miraki-Moud, F
Ermini, L
Titley, I
Vijayaraghavan, G
Papaemmanuil, E
Campbell, P
Gribben, J
Taussig, D
Greaves, M
Document Type
Journal Article
Date
2019-05-01
Date Accepted
2018-11-06
Abstract
We used single cell Q-PCR on a micro-fluidic platform (Fluidigm) to analyse clonal, genetic architecture and phylogeny in acute myeloid leukaemia (AML) using selected mutations. Ten cases of NPM1c mutant AML were screened for 111 mutations that are recurrent in AML and cancer. Clonal architectures were relatively simple with one to six sub-clones and were branching in some, but not all, patients. NPM1 mutations were secondary or sub-clonal to other driver mutations (DNM3TA, TET2, WT1 and IDH2) in all cases. In three of the ten cases, single cell analysis of enriched CD34+/CD33- cells revealed a putative pre-leukaemic sub-clone, undetectable in the bulk CD33+ population that had one or more driver mutations but lacked NPM1c. Cells from all cases were transplanted into NSG mice and in most (8/10), more than one sub-clone (#2-5 sub-clones) transplanted. However, the dominant regenerating sub-clone in 9/10 cases was NPM1+ and this sub-clone was either dominant or minor in the diagnostic sample from which it was derived. This study provides further evidence, at the single cell level, for genetic variegation in sub-clones and stem cells in acute leukaemia and demonstrates both a preferential order of mutation accrual and parallel evolution of sub-clones.
Citation
Leukemia, 2019, 33 (5), pp. 1113 - 1123
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
0887-6924
eISSN
1476-5551
Collections
Research Team
Acute Leukaemia
Biology of Childhood Leukaemia
Biology of Childhood Leukaemia