On the origin of multiple mutant clones in paroxysmal nocturnal hemoglobinuria

Arne Traulsen, Jorge M. Pacheco, David Dingli

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3081-3084
Number of pages4
JournalStem Cells
Issue number12
StatePublished - Dec 2007

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology


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