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Somatic mutations and the hierarchy of hematopoiesis
Author(s) -
Traulsen Arne,
Pacheco Jorge M.,
Luzzatto Lucio,
Dingli David
Publication year - 2010
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.201000025
Subject(s) - biology , mutation , haematopoiesis , genetics , clone (java method) , germline mutation , somatic cell , somatic evolution in cancer , paroxysmal nocturnal hemoglobinuria , population , myeloid leukemia , myeloid , leukemia , suppressor mutation , hematopoietic stem cell , cancer research , stem cell , gene , immunology , medicine , environmental health
Clonal disease is often regarded as almost synonymous with cancer. However, it is becoming increasingly clear that our bodies harbor numerous mutant clones that are not tumors, and mostly give rise to no disease at all. Here we discuss three somatic mutations arising within the hematopoietic system: BCR‐ABL , characteristic of chronic myeloid leukemia; mutations of the PIG‐A gene, characteristic of paroxysmal nocturnal hemoglobinuria; the V617F mutation in the JAK2 gene, characteristic of myeloproliferative diseases. The population frequencies of these three blood disorders fit well with a hierarchical model of hematopoiesis. The fate of any mutant clone will depend on the target cell and on the fitness advantage, if any, that the mutation confers on the cell. In general, we can expect that only a mutation in a hematopoietic stem cell will give long‐term disease; the same mutation taking place in a cell located more downstream may produce just a ripple in the hematopoietic ocean.