Clone Wars — The Emergence of Neoplastic Blood-Cell Clones with Aging
Menées à l'aide d'une technique de séquençage de l'exome entier à partir d'échantillons sanguins prélevés sur 17 182 et 12 380 participants inclus dans deux cohortes indépendantes, ces études identifient la présence, croissante avec l'âge, de mutations somatiques associées à un risque de cancer hématologique
Blood cells originate from hematopoietic stem cells (HSCs). HSCs are infrequent (<2 per 108 bone marrow cells, or about 11,000 to 22,000 per person) and rarely divide. Because mutations occur with DNA replication during cell division, HSC quiescence maximizes genomic stability and thus safety.
Mutations, however, can and do occur. Most are innocuous and do not substantially alter protein quantities or structure. Some make subtle changes that contribute to cellular diversity and allow HSCs or their offspring to react efficiently to differing environmental stresses. However, if a mutation speeds HSC self-renewal divisions or slows apoptosis, this results in more replicate HSCs, a larger clone size, and a disproportionate contribution by the mutant HSC to blood-cell production...
New England Journal of Medicine , éditorial en libre accès, 2013