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Gene expression profiling of leukemic cell lines reveals conserved molecular signatures among subtypes with specific genetic aberrations

Andersson, Anna LU ; Edén, Patrik LU ; Lindgren, David LU ; Nilsson, Jens LU ; Lassen, Carin LU ; Heldrup, Jesper LU ; Fontes, Magnus LU ; Borg, Åke LU ; Mitelman, Felix LU and Johansson, Bertil LU , et al. (2005) In Leukemia 19(6). p.1042-1050
Abstract
Hematologic malignancies are characterized by fusion genes of biological/clinical importance. Immortalized cell lines with such aberrations are today widely used to model different aspects of leukemogenesis. Using cDNA microarrays, we determined the gene expression profiles of 40 cell lines as well as of primary leukemias harboring 11q23/MLL rearrangements, t(1;19)[TCF3/PBX1], t(12;21)[ETV6/RUNX1], t(8;21)[RUNX1/CBFA2T1], t(8;14) [IGH@/MYC], t(8;14)[TRA@/MYC], t(9;22)[BCR/ABL1], t(10;11) [PICALM/MLLT10], t(15;17)[PML/RARA], or inv(16)[CBFB/MYH11]. Unsupervised classification revealed that hematopoietic cell lines of diverse origin, but with the same primary genetic changes, segregated together, suggesting that pathogenetically important... (More)
Hematologic malignancies are characterized by fusion genes of biological/clinical importance. Immortalized cell lines with such aberrations are today widely used to model different aspects of leukemogenesis. Using cDNA microarrays, we determined the gene expression profiles of 40 cell lines as well as of primary leukemias harboring 11q23/MLL rearrangements, t(1;19)[TCF3/PBX1], t(12;21)[ETV6/RUNX1], t(8;21)[RUNX1/CBFA2T1], t(8;14) [IGH@/MYC], t(8;14)[TRA@/MYC], t(9;22)[BCR/ABL1], t(10;11) [PICALM/MLLT10], t(15;17)[PML/RARA], or inv(16)[CBFB/MYH11]. Unsupervised classification revealed that hematopoietic cell lines of diverse origin, but with the same primary genetic changes, segregated together, suggesting that pathogenetically important regulatory networks remain conserved despite numerous passages. Moreover, primary leukemias cosegregated with cell lines carrying identical genetic rearrangements, further supporting that critical regulatory pathways remain intact in hematopoietic cell lines. Transcriptional signatures correlating with clinical subtypes/primary genetic changes were identified and annotated based on their biological/molecular properties and chromosomal localization. Furthermore, the expression profile of tyrosine kinase-encoding genes was investigated, identifying several differentially expressed members, segregating with primary genetic changes, which may be targeted with tyrosine kinase inhibitors. The identified conserved signatures are likely to reflect regulatory networks of importance for the transforming abilities of the primary genetic changes and offer important pathogenetic insights as well as a number of targets for future rational drug design. (Less)
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Contribution to journal
publication status
published
subject
keywords
cDNA microarray, AML, CML-BC, ALL, pediatric leukemia
in
Leukemia
volume
19
issue
6
pages
1042 - 1050
publisher
Nature Publishing Group
external identifiers
  • pmid:15843827
  • wos:000229323900024
  • scopus:20844431689
ISSN
1476-5551
DOI
10.1038/sj.leu.2403749
language
English
LU publication?
yes
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30b7e5cf-90cb-42ad-9446-f9e28ab2da50 (old id 238962)
date added to LUP
2007-08-14 08:29:16
date last changed
2017-10-22 04:48:28
@article{30b7e5cf-90cb-42ad-9446-f9e28ab2da50,
  abstract     = {Hematologic malignancies are characterized by fusion genes of biological/clinical importance. Immortalized cell lines with such aberrations are today widely used to model different aspects of leukemogenesis. Using cDNA microarrays, we determined the gene expression profiles of 40 cell lines as well as of primary leukemias harboring 11q23/MLL rearrangements, t(1;19)[TCF3/PBX1], t(12;21)[ETV6/RUNX1], t(8;21)[RUNX1/CBFA2T1], t(8;14) [IGH@/MYC], t(8;14)[TRA@/MYC], t(9;22)[BCR/ABL1], t(10;11) [PICALM/MLLT10], t(15;17)[PML/RARA], or inv(16)[CBFB/MYH11]. Unsupervised classification revealed that hematopoietic cell lines of diverse origin, but with the same primary genetic changes, segregated together, suggesting that pathogenetically important regulatory networks remain conserved despite numerous passages. Moreover, primary leukemias cosegregated with cell lines carrying identical genetic rearrangements, further supporting that critical regulatory pathways remain intact in hematopoietic cell lines. Transcriptional signatures correlating with clinical subtypes/primary genetic changes were identified and annotated based on their biological/molecular properties and chromosomal localization. Furthermore, the expression profile of tyrosine kinase-encoding genes was investigated, identifying several differentially expressed members, segregating with primary genetic changes, which may be targeted with tyrosine kinase inhibitors. The identified conserved signatures are likely to reflect regulatory networks of importance for the transforming abilities of the primary genetic changes and offer important pathogenetic insights as well as a number of targets for future rational drug design.},
  author       = {Andersson, Anna and Edén, Patrik and Lindgren, David and Nilsson, Jens and Lassen, Carin and Heldrup, Jesper and Fontes, Magnus and Borg, Åke and Mitelman, Felix and Johansson, Bertil and Höglund, Mattias and Fioretos, Thoas},
  issn         = {1476-5551},
  keyword      = {cDNA microarray,AML,CML-BC,ALL,pediatric leukemia},
  language     = {eng},
  number       = {6},
  pages        = {1042--1050},
  publisher    = {Nature Publishing Group},
  series       = {Leukemia},
  title        = {Gene expression profiling of leukemic cell lines reveals conserved molecular signatures among subtypes with specific genetic aberrations},
  url          = {http://dx.doi.org/10.1038/sj.leu.2403749},
  volume       = {19},
  year         = {2005},
}