Abstract
Mutations are a natural consequence of the interactions of our genome with genotoxic agents and imperfections in the DNA replication machinery. Every cell is at risk of mutations and therefore the probability of acquiring mutations is increasing with population size. However, the impact of a mutation depends on the type of cell where it occurs and the average lifetime of that cell. Tissue architecture is organized in such a way that many mutations will have no consequence, although the cell harboring them may expand into a detectable clone. We will use the known architecture and dynamics of hematopoiesis to describe the evolution of mutant clones in age structured populations and show why the appearance of well recognized mutations is inevitable even if usually of no consequence. Most mutant populations merely cause transient ripples in a tissue. However, whenever mutations occur in stem cells or other primitive cells, the associated clones can have long lasting consequences and may lead to disease.
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References
Araten DJ, Nafa K, Pakdeesuwan K, Luzzatto L (1999) Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals. Proc Natl Acad Sci USA 96:5209–5214
Beer PA, Jones AV, Bench AJ, Goday-Fernandez A, Boyd EM, Vaghela KJ, Erber WN, Odeh B, Wright C, McMullin MF, Cullis J, Huntly BJ, Harrison CN, Cross NC, Green AR (2009) Clonal diversity in the myeloproliferative neoplasms: independent origins of genetically distinct clones. Brx J Haematol 144:904–908
Bessler M, Mason P, Hillmen P, Luzzatto L (1994a) Somatic mutations and cellular selection in paroxysmal nocturnal haemoglobinuria. Lancet 343:951–953
Bessler M, Mason PJ, Hillmen P, Luzzatto L (1994b) Mutations in the PIG-A gene causing partial deficiency of GPI-linked surface proteins (PNH II) in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol 87:863–866
Bose S, Deininger M, Gora-Tybor J, Goldman JM, Melo JV (1998) The presence of typical and atypical BCR-ABL fusion genes in leukocytes of normal individuals: biologic significance and implications for the assessment of minimal residual disease. Blood 92:3362–3367
Daley GQ, Van Etten RA, Baltimore D (1990) Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 247:824–830
Dingli D, Pacheco JM (2006) Allometric scaling of the active hematopoietic stem cell pool across mammals. PLoS One 1:e2
Dingli D, Traulsen A, Pacheco JM (2007a) Compartmental architecture and dynamics of hematopoiesis. PLoS One 2:e345
Dingli D, Traulsen A, Pacheco JM (2007b) Stochastic dynamics of hematopoietic tumor stem cells. Cell Cycle 6:461–466
Dingli D, Pacheco JM, Traulsen A (2008a) Multiple mutant clones in blood rarely coexist. Phys Rev E Stat Nonlin Soft Matter Phys 77:021915
Dingli D, Luzzatto L, Pacheco JM (2008b) Neutral evolution in paroxysmal nocturnal hemoglobinuria. Proc Natl Acad Sci USA 105:18496–18500
Dingli D, Traulsen A, Pacheco JM (2008c) Chronic myeloid leukemia: origin, development, response to therapy, and relapse. Clin Leuk 2:133–139
Dingli D, Antal T, Traulsen A, Pacheco JM (2009) Progenitor cell self-renewal and cyclic neutropenia. Cell Prolif 42:330–338
Dingli D, Traulsen A, Lenaerts T, Pacheco JM (2010) Evolutionary dynamics of chronic myeloid leukemia. Genes Cancer 1:309–315
Goldman JM, Melo JV (2003) Chronic myeloid leukemia–advances in biology and new approaches to treatment. N Engl J Med 349:1451–1464
Guibal FC, Alberich-Jorda M, Hirai H, Ebralidze A, Levantini E, Di Ruscio A, Zhang P, Santana-Lemos BA, Neuberg D, Wagers AJ, Rego EM, Tenen DG (2009) Identification of a myeloid committed progenitor as the cancer-initiating cell in acute promyelocytic leukemia. Blood 114:5415–5425
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674
Inoue N, Izui-Sarumaru T, Murakami Y, Endo Y, Nishimura J, Kurokawa K, Kuwayama M, Shime H, Machii T, Kanakura Y, Meyers G, Wittwer C, Chen Z, Babcock W, Frei-Lahr D, Parker CJ, Kinoshita T (2006) Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH). Blood 108:4232–4236
Jamieson CH, Gotlib J, Durocher JA, Chao MP, Mariappan MR, Lay M, Jones C, Zehnder JL, Lilleberg SL, Weissman IL (2006) The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation. Proc Natl Acad Sci USA 103:6224–6229
Johnston MD, Edwards CM, Bodmer WF, Maini PK, Chapman SJ (2007) Mathematical modeling of cell population dynamics in the colonic crypt and in colorectal cancer. Proc Natl Acad Sci USA 104:4008–4013
Lenaerts T, Pacheco JM, Traulsen A, Dingli D (2010) Tyrosine kinase inhibitor therapy can cure chronic myeloid leukemia without hitting leukemic stem cells. Haematologica 95:900–907
Lucas JN, Hill FS, Burk CE, Lewis AD, Lucas AK, Chen AM, Sailes FC, Straume T (1997) Dose-response curve for chromosome translocations induced by low dose rate 137Cs gamma rays. Radiat Prot Dosimetry 71:279–282
Luzzatto L, Bessler M, Rotoli B (1997) Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise? Cell 88:1–4
McCulloch EA, Till JE (1964) Proliferation of hemopoietic colony-forming cells transplanted into irradiated mice. Radiat Res 22:383–397
Nielsen C, Birgens HS, Nordestgaard BG, Kjaer L, Bojesen SE (2011) The JAK2 V617F somatic mutation, mortality and cancer risk in the general population. Haematologica 96:450–453
Pacheco JM, Traulsen A, Dingli D (2009) The allometry of chronic myeloid leukemia. J Theor Biol 259:635–640
Rowley JD (1973) Letter: a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243:290–293
Traulsen A, Pacheco JM, Dingli D (2007) On the origin of multiple mutant clones in paroxysmal nocturnal hemoglobinuria. Stem Cells 25:3081–3084
Traulsen A, Pacheco JM, Luzzatto L, Dingli D (2010) Somatic mutations and the hierarchy of hematopoiesis. Bioessays 32:1003–1008
Vainchenker W, Constantinescu SN (2005) A unique activating mutation in JAK2 (V617F) is at the origin of polycythemia vera and allows a new classification of myeloproliferative diseases. Hematol Am Soc Hematol Educ Program 195–200
Xu X, Zhang Q, Luo J, Xing S, Li Q, Krantz SB, Fu X, Zhao ZJ (2007) JAK2(V617F): prevalence in a large Chinese hospital population. Blood 109:339–342
Acknowledgments
David Dingli is supported by the Minnesota Partnership for Biotechnology and Medical Genomics. Arne Traulsen is funded by the Emmy-Noether program of the DFG, DAAD (project 0813008) and the Max Planck Society. Jorge M. Pacheco is supported by FCT-Portugal and DAAD.
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Dingli, D., Traulsen, A., Pacheco, J.M. (2012). Evolutionary Dynamics of Mutations in Hematopoietic Stem Cells and Beyond. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells,Volume 3. Stem Cells and Cancer Stem Cells, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2415-0_11
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DOI: https://doi.org/10.1007/978-94-007-2415-0_11
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