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

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

Andersson, Anna (author): Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine

Edén, Patrik (author): Lund University,Lunds universitet,Beräkningsbiologi och biologisk fysik - Genomgår omorganisation,Institutionen för astronomi och teoretisk fysik - Genomgår omorganisation,Naturvetenskapliga fakulteten,Computational Biology and Biological Physics - Undergoing reorganization,Department of Astronomy and Theoretical Physics - Undergoing reorganization,Faculty of Science

Lindgren, David (author): Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Division of Clinical Genetics,Department of Laboratory Medicine

Nilsson, Jens (author): Lund University,Lunds universitet,Matematik LTH,Matematikcentrum,Institutioner vid LTH,Lunds Tekniska Högskola,Mathematics (Faculty of Engineering),Centre for Mathematical Sciences,Departments at LTH,Faculty of Engineering, LTH

Lassen, Carin (author): Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine

Heldrup, Jesper (author): Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine

Fontes, Magnus (author): Lund University,Lunds universitet,Matematik LTH,Matematikcentrum,Institutioner vid LTH,Lunds Tekniska Högskola,Mathematics (Faculty of Engineering),Centre for Mathematical Sciences,Departments at LTH,Faculty of Engineering, LTH

Borg, Åke (author): Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine

Mitelman, Felix (author): Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine

Johansson, Bertil (author): Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine

Höglund, Mattias (author): Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Division of Clinical Genetics,Department of Laboratory Medicine

Fioretos, Thoas (author): Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine

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2005-04-21
2005
English.
In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 19:6, s. 1042-1050

Related links:: http://dx.doi.org/10...; show more...; https://www.nature.c...; https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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.

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By the author/editor: Andersson, Anna; Edén, Patrik; Lindgren, David; Nilsson, Jens; Lassen, Carin; Heldrup, Jesper; show more...; Fontes, Magnus; Borg, Åke; Mitelman, Felix; Johansson, Berti ...; Höglund, Mattias; Fioretos, Thoas; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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

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