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. Author manuscript; available in PMC: 2010 Apr 1.

Published in final edited form as: Hematol Oncol Clin North Am. 2009 Apr;23(2):361–376. doi: 10.1016/j.hoc.2009.01.006

The fitness landscape for hematopoietic stem cells. A. A popular model of clonal evolution in hematopoietic stem cells proposes that somatic mutations occur stochastically in hematopoietic stem cells and that rare mutations of this kind confer upon the mutant stem cell (red) an inherent proliferative/survival advantage over the non mutant (blue) stem cells. A key principle of this model is that the non mutant stem cells are not unfit, at least at the time the new clone initially evolves. The fitness differences between the evolving clone and the normal stem cell pool can be described as a selection coefficient, here given a value of X. B. An alternative model, one more consistent with studies on clonal evolution in the setting of marrow failure is one in which the entire population of normal hematopoietic stem cells is unfit as a result of environmental stress. A somatic mutant (red) stem cell has developed resistance to the specific environmental stressor so remains fit while the remainder of the stem cell pool has become unfit as a result of environmental stress. In this instance the coefficient for selection of the abnormal clone is identical (X) to that of the model described in A.

The fitness landscape for hematopoietic stem cells. A. A popular model of clonal evolution in hematopoietic stem cells proposes that somatic mutations occur stochastically in hematopoietic stem cells and that rare mutations of this kind confer upon the mutant stem cell (red) an inherent proliferative/survival advantage over the non mutant (blue) stem cells. A key principle of this model is that the non mutant stem cells are not unfit, at least at the time the new clone initially evolves. The fitness differences between the evolving clone and the normal stem cell pool can be described as a selection coefficient, here given a value of X. B. An alternative model, one more consistent with studies on clonal evolution in the setting of marrow failure is one in which the entire population of normal hematopoietic stem cells is unfit as a result of environmental stress. A somatic mutant (red) stem cell has developed resistance to the specific environmental stressor so remains fit while the remainder of the stem cell pool has become unfit as a result of environmental stress. In this instance the coefficient for selection of the abnormal clone is identical (X) to that of the model described in A.