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The fundamental prevalence of chronic myeloid leukemia-generating clonogenic cells in the light of the neutrality theory of evolution

Jankovic, G M; Pavlovic, M; Vukomanovic, D J; Colovic, M D and Lazarevic, V LU (2002) In Blood Cells, Molecules, and Diseases 27(5). p.7-913
Abstract

A variety of normal human tissues have been reported to harbor small cell populations carrying potentially oncogenic gene rearrangements. This backdrop of mutant cells may be present in the majority of healthy individuals and is apparently weakly selected against. This may provide empirical support for the concept of global neutrality, or near-neutrality (very weak selection), of many somatic mutations. Many healthy individuals, as well as patients with chronic myeloid leukemia, manifest the BCR-ABL fusion gene in blood cells. The presumed neutrality of the BCR-ABL rearrangement-carrying pluripotential hematopoietic stem cells and the relative uniformity of the incidence rate of CML worldwide were used to estimate the extent of the... (More)

A variety of normal human tissues have been reported to harbor small cell populations carrying potentially oncogenic gene rearrangements. This backdrop of mutant cells may be present in the majority of healthy individuals and is apparently weakly selected against. This may provide empirical support for the concept of global neutrality, or near-neutrality (very weak selection), of many somatic mutations. Many healthy individuals, as well as patients with chronic myeloid leukemia, manifest the BCR-ABL fusion gene in blood cells. The presumed neutrality of the BCR-ABL rearrangement-carrying pluripotential hematopoietic stem cells and the relative uniformity of the incidence rate of CML worldwide were used to estimate the extent of the background of BCR-ABL-positive stem cells and the numerical size of the human pluripotential hematopoietic stem cell pool. Three different approaches (molecular-epidemiological, statistical, and population genetical) were employed. Each resulted in very similar estimates of the size of the stem cells carrying the BCR-ABL allele fusions (1.4 x 10(4) cells) and the size of the total human stem cell pool (1.6 x 10(9) cells per individual). The implication of these estimates in the context of the hierarchical nature of the stem cell pool is also considered. The presumptive smaller-sized population of CD34(-) stem cells could not be characterized by any of the approaches used as a "founding" population, representing an ultimate source of all hematopoietic progenitors, or as a subset of stem cells comprising a deeper "kinetic" segment of the total (10(9)-sized) stem cell compartment.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Cell Survival, Cell Transformation, Neoplastic, Clone Cells, Evolution, Molecular, Fusion Proteins, bcr-abl, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Models, Genetic, Mutation, Neoplastic Stem Cells, Poisson Distribution, Prevalence
in
Blood Cells, Molecules, and Diseases
volume
27
issue
5
pages
5 pages
publisher
Elsevier
external identifiers
  • Scopus:0035207087
ISSN
1079-9796
DOI
10.1006/bcmd.2001.0462
language
English
LU publication?
no
id
ade970aa-7bc8-4bf0-8b11-61d2224ddb7d
date added to LUP
2016-05-24 17:25:10
date last changed
2016-10-13 05:09:25
@misc{ade970aa-7bc8-4bf0-8b11-61d2224ddb7d,
  abstract     = {<p>A variety of normal human tissues have been reported to harbor small cell populations carrying potentially oncogenic gene rearrangements. This backdrop of mutant cells may be present in the majority of healthy individuals and is apparently weakly selected against. This may provide empirical support for the concept of global neutrality, or near-neutrality (very weak selection), of many somatic mutations. Many healthy individuals, as well as patients with chronic myeloid leukemia, manifest the BCR-ABL fusion gene in blood cells. The presumed neutrality of the BCR-ABL rearrangement-carrying pluripotential hematopoietic stem cells and the relative uniformity of the incidence rate of CML worldwide were used to estimate the extent of the background of BCR-ABL-positive stem cells and the numerical size of the human pluripotential hematopoietic stem cell pool. Three different approaches (molecular-epidemiological, statistical, and population genetical) were employed. Each resulted in very similar estimates of the size of the stem cells carrying the BCR-ABL allele fusions (1.4 x 10(4) cells) and the size of the total human stem cell pool (1.6 x 10(9) cells per individual). The implication of these estimates in the context of the hierarchical nature of the stem cell pool is also considered. The presumptive smaller-sized population of CD34(-) stem cells could not be characterized by any of the approaches used as a "founding" population, representing an ultimate source of all hematopoietic progenitors, or as a subset of stem cells comprising a deeper "kinetic" segment of the total (10(9)-sized) stem cell compartment.</p>},
  author       = {Jankovic, G M and Pavlovic, M and Vukomanovic, D J and Colovic, M D and Lazarevic, V},
  issn         = {1079-9796},
  keyword      = {Cell Survival,Cell Transformation, Neoplastic,Clone Cells,Evolution, Molecular,Fusion Proteins, bcr-abl,Humans,Leukemia, Myelogenous, Chronic, BCR-ABL Positive,Models, Genetic,Mutation,Neoplastic Stem Cells,Poisson Distribution,Prevalence},
  language     = {eng},
  month        = {01},
  number       = {5},
  pages        = {7--913},
  publisher    = {ARRAY(0xbfb3ac0)},
  series       = {Blood Cells, Molecules, and Diseases},
  title        = {The fundamental prevalence of chronic myeloid leukemia-generating clonogenic cells in the light of the neutrality theory of evolution},
  url          = {http://dx.doi.org/10.1006/bcmd.2001.0462},
  volume       = {27},
  year         = {2002},
}