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Pediatric T-cell acute lymphoblastic leukemia

Karrman, Kristina LU and Johansson, Bertil LU (2017) In Genes Chromosomes and Cancer 56(2). p.89-116
Abstract

The most common pediatric malignancy is acute lymphoblastic leukemia (ALL), of which T-cell ALL (T-ALL) comprises 10–15% of cases. T-ALL arises in the thymus from an immature thymocyte as a consequence of a stepwise accumulation of genetic and epigenetic aberrations. Crucial biological processes, such as differentiation, self-renewal capacity, proliferation, and apoptosis, are targeted and deranged by several types of neoplasia-associated genetic alteration, for example, translocations, deletions, and mutations of genes that code for proteins involved in signaling transduction, epigenetic regulation, and transcription. Epigenetically, T-ALL is characterized by gene expression changes caused by hypermethylation of tumor suppressor genes,... (More)

The most common pediatric malignancy is acute lymphoblastic leukemia (ALL), of which T-cell ALL (T-ALL) comprises 10–15% of cases. T-ALL arises in the thymus from an immature thymocyte as a consequence of a stepwise accumulation of genetic and epigenetic aberrations. Crucial biological processes, such as differentiation, self-renewal capacity, proliferation, and apoptosis, are targeted and deranged by several types of neoplasia-associated genetic alteration, for example, translocations, deletions, and mutations of genes that code for proteins involved in signaling transduction, epigenetic regulation, and transcription. Epigenetically, T-ALL is characterized by gene expression changes caused by hypermethylation of tumor suppressor genes, histone modifications, and miRNA and lncRNA abnormalities. Although some genetic and gene expression patterns have been associated with certain clinical features, such as immunophenotypic subtype and outcome, none has of yet generally been implemented in clinical routine for treatment decisions. The recent advent of massive parallel sequencing technologies has dramatically increased our knowledge of the genetic blueprint of T-ALL, revealing numerous fusion genes as well as novel gene mutations. The challenges now are to integrate all genetic and epigenetic data into a coherent understanding of the pathogenesis of T-ALL and to translate the wealth of information gained in the last few years into clinical use in the form of improved risk stratification and targeted therapies. Here, we provide an overview of pediatric T-ALL with an emphasis on the acquired genetic alterations that result in this disease.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes Chromosomes and Cancer
volume
56
issue
2
pages
28 pages
publisher
John Wiley & Sons
external identifiers
  • scopus:84997771403
  • wos:000394426200001
ISSN
1045-2257
DOI
10.1002/gcc.22416
language
English
LU publication?
yes
id
6845f2e4-25bb-4168-adb6-a37fab2afe6b
date added to LUP
2017-02-03 12:30:41
date last changed
2018-05-06 04:30:29
@article{6845f2e4-25bb-4168-adb6-a37fab2afe6b,
  abstract     = {<p>The most common pediatric malignancy is acute lymphoblastic leukemia (ALL), of which T-cell ALL (T-ALL) comprises 10–15% of cases. T-ALL arises in the thymus from an immature thymocyte as a consequence of a stepwise accumulation of genetic and epigenetic aberrations. Crucial biological processes, such as differentiation, self-renewal capacity, proliferation, and apoptosis, are targeted and deranged by several types of neoplasia-associated genetic alteration, for example, translocations, deletions, and mutations of genes that code for proteins involved in signaling transduction, epigenetic regulation, and transcription. Epigenetically, T-ALL is characterized by gene expression changes caused by hypermethylation of tumor suppressor genes, histone modifications, and miRNA and lncRNA abnormalities. Although some genetic and gene expression patterns have been associated with certain clinical features, such as immunophenotypic subtype and outcome, none has of yet generally been implemented in clinical routine for treatment decisions. The recent advent of massive parallel sequencing technologies has dramatically increased our knowledge of the genetic blueprint of T-ALL, revealing numerous fusion genes as well as novel gene mutations. The challenges now are to integrate all genetic and epigenetic data into a coherent understanding of the pathogenesis of T-ALL and to translate the wealth of information gained in the last few years into clinical use in the form of improved risk stratification and targeted therapies. Here, we provide an overview of pediatric T-ALL with an emphasis on the acquired genetic alterations that result in this disease.</p>},
  author       = {Karrman, Kristina and Johansson, Bertil},
  issn         = {1045-2257},
  language     = {eng},
  month        = {02},
  number       = {2},
  pages        = {89--116},
  publisher    = {John Wiley & Sons},
  series       = {Genes Chromosomes and Cancer},
  title        = {Pediatric T-cell acute lymphoblastic leukemia},
  url          = {http://dx.doi.org/10.1002/gcc.22416},
  volume       = {56},
  year         = {2017},
}