On the Origin of Multiple Mutant Clones in Paroxysmal Nocturnal Hemoglobinuria
Article first published online: 6 SEP 2007
Copyright © 2007 AlphaMed Press
Volume 25, Issue 12, pages 3081–3084, December 2007
How to Cite
Traulsen, A., Pacheco, J. M. and Dingli, D. (2007), On the Origin of Multiple Mutant Clones in Paroxysmal Nocturnal Hemoglobinuria. STEM CELLS, 25: 3081–3084. doi: 10.1634/stemcells.2007-0427
- Issue published online: 2 JAN 2009
- Article first published online: 6 SEP 2007
- Manuscript Accepted: 14 AUG 2007
- Manuscript Received: 1 JUN 2007
The pool of hematopoietic stem cells that actively contributes to hematopoiesis is small, and the cells replicate slowly. Patients with paroxysmal nocturnal hemoglobinuria invariably have a mutation in the PIG-A gene, and many have more than one clone of PIG-A mutated cells. Typically there is a dominant clone and a smaller second clone. By using a combination of stochastic dynamics and models of hematopoiesis, we show that it is very unlikely that more than one PIG-A mutated clone arises at the level of the hematopoietic stem cells. More likely, the smaller clone develops in the progenitor cell pool that would be expected to contribute to hematopoiesis for a shorter period of time. We provide estimates for the duration of these contributions and testable hypotheses that can shed important insights on this acquired hematopoietic stem cell disorder.
Disclosure of potential conflicts of interest is found at the end of this article.