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Gene expression signatures in childhood acute leukemias are largely unique and distinct from those of normal tissues and other malignancies.

Andersson, Anna LU ; Edén, Patrik; Olofsson, Tor LU and Fioretos, Thoas LU (2010) In BMC Medical Genomics 3.
Abstract
BACKGROUND: Childhood leukemia is characterized by the presence of balanced chromosomal translocations or by other structural or numerical chromosomal changes. It is well know that leukemias with specific molecular abnormalities display profoundly different global gene expression profiles. However, it is largely unknown whether such subtype-specific leukemic signatures are unique or if they are active also in non-hematopoietic normal tissues or in other human cancer types. METHODS: Using gene set enrichment analysis, we systematically explored whether the transcriptional programs in childhood acute lymphoblastic leukemia (ALL) and myeloid leukemia (AML) were significantly similar to those in different flow-sorted subpopulations of normal... (More)
BACKGROUND: Childhood leukemia is characterized by the presence of balanced chromosomal translocations or by other structural or numerical chromosomal changes. It is well know that leukemias with specific molecular abnormalities display profoundly different global gene expression profiles. However, it is largely unknown whether such subtype-specific leukemic signatures are unique or if they are active also in non-hematopoietic normal tissues or in other human cancer types. METHODS: Using gene set enrichment analysis, we systematically explored whether the transcriptional programs in childhood acute lymphoblastic leukemia (ALL) and myeloid leukemia (AML) were significantly similar to those in different flow-sorted subpopulations of normal hematopoietic cells (n = 8), normal non-hematopoietic tissues (n = 22) or human cancer tissues (n = 13). RESULTS: This study revealed that e.g., the t(12;21) [ETV6-RUNX1] subtype of ALL and the t(15;17) [PML-RARA] subtype of AML had transcriptional programs similar to those in normal Pro-B cells and promyelocytes, respectively. Moreover, the 11q23/MLL subtype of ALL showed similarities with non-hematopoietic tissues. Strikingly however, most of the transcriptional programs in the other leukemic subtypes lacked significant similarity to approximately 100 gene sets derived from normal and malignant tissues. CONCLUSIONS: This study demonstrates, for the first time, that the expression profiles of childhood leukemia are largely unique, with limited similarities to transcriptional programs active in normal hematopoietic cells, non-hematopoietic normal tissues or the most common forms of human cancer. In addition to providing important pathogenetic insights, these findings should facilitate the identification of candidate genes or transcriptional programs that can be used as unique targets in leukemia. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
in
BMC Medical Genomics
volume
3
publisher
BioMed Central
external identifiers
  • WOS:000276388300001
  • PMID:20211010
  • Scopus:77950275744
ISSN
1755-8794
DOI
10.1186/1755-8794-3-6
language
English
LU publication?
yes
id
4e47b5cf-458b-4e90-9483-2ba34fc38a13 (old id 1582461)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20211010?dopt=Abstract
date added to LUP
2010-04-07 15:06:10
date last changed
2016-10-30 04:35:17
@misc{4e47b5cf-458b-4e90-9483-2ba34fc38a13,
  abstract     = {BACKGROUND: Childhood leukemia is characterized by the presence of balanced chromosomal translocations or by other structural or numerical chromosomal changes. It is well know that leukemias with specific molecular abnormalities display profoundly different global gene expression profiles. However, it is largely unknown whether such subtype-specific leukemic signatures are unique or if they are active also in non-hematopoietic normal tissues or in other human cancer types. METHODS: Using gene set enrichment analysis, we systematically explored whether the transcriptional programs in childhood acute lymphoblastic leukemia (ALL) and myeloid leukemia (AML) were significantly similar to those in different flow-sorted subpopulations of normal hematopoietic cells (n = 8), normal non-hematopoietic tissues (n = 22) or human cancer tissues (n = 13). RESULTS: This study revealed that e.g., the t(12;21) [ETV6-RUNX1] subtype of ALL and the t(15;17) [PML-RARA] subtype of AML had transcriptional programs similar to those in normal Pro-B cells and promyelocytes, respectively. Moreover, the 11q23/MLL subtype of ALL showed similarities with non-hematopoietic tissues. Strikingly however, most of the transcriptional programs in the other leukemic subtypes lacked significant similarity to approximately 100 gene sets derived from normal and malignant tissues. CONCLUSIONS: This study demonstrates, for the first time, that the expression profiles of childhood leukemia are largely unique, with limited similarities to transcriptional programs active in normal hematopoietic cells, non-hematopoietic normal tissues or the most common forms of human cancer. In addition to providing important pathogenetic insights, these findings should facilitate the identification of candidate genes or transcriptional programs that can be used as unique targets in leukemia.},
  author       = {Andersson, Anna and Edén, Patrik and Olofsson, Tor and Fioretos, Thoas},
  issn         = {1755-8794},
  language     = {eng},
  publisher    = {ARRAY(0x8e90480)},
  series       = {BMC Medical Genomics},
  title        = {Gene expression signatures in childhood acute leukemias are largely unique and distinct from those of normal tissues and other malignancies.},
  url          = {http://dx.doi.org/10.1186/1755-8794-3-6},
  volume       = {3},
  year         = {2010},
}