Traulsen Arne, Pacheco Jorge M, Dingli David
Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, USA.
Stem Cells. 2007 Dec;25(12):3081-4. doi: 10.1634/stemcells.2007-0427. Epub 2007 Sep 6.
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.
积极参与造血的造血干细胞池很小，且细胞复制缓慢。阵发性夜间血红蛋白尿患者的PIG-A基因 invariably 存在突变，许多患者有不止一个PIG-A突变细胞克隆。通常有一个占主导地位的克隆和一个较小的第二个克隆。通过结合随机动力学和造血模型，我们表明在造血干细胞水平上出现不止一个PIG-A突变克隆的可能性非常小。更有可能的是，较小的克隆在祖细胞池中发展，预计该祖细胞池对造血的贡献时间较短。我们提供了这些贡献持续时间的估计以及可检验的假设，这些假设可以为这种获得性造血干细胞疾病提供重要见解。潜在利益冲突的披露见本文末尾。
