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Gene Expression Profiling and Microarrays

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

Leukemia volume 19, pages 1042–1050 (2005)Cite this article

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.

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Acknowledgements

We thank the Swegene DNA microarray resource center in Lund, supported by the Knut and Alice Wallenberg Foundation through the Swegene consortium, Eva Pålsson for cytogenetic analysis, and Srinivas Veerla for useful computational program construction. PE was supported by the Swedish Foundation for Strategic Research through the Lund Center for Stem Cell Biology and Cell Therapy. JN was supported by the Knowledge Foundation and AstraZeneca R&D Lund. This study was supported by the Swedish Cancer Society, The Swedish Children's Cancer Foundation, the Medical Faculty of Lund University, and the IngaBritt and Arne Lundberg foundation.

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Authors and Affiliations

  1. Department of Clinical Genetics, Lund University Hospital, Sweden

    A Andersson, D Lindgren, C Lassen, F Mitelman, B Johansson, M Höglund & T Fioretos

  2. Department of Complex Systems, Theoretical Physics, Lund University, Sweden

    P Edén

  3. Center for Mathematical Sciences, Lund University, Sweden

    J Nilsson & M Fontes

  4. Department of Pediatrics, Lund University Hospital, Sweden

    J Heldrup

  5. Department of Oncology, Lund University Hospital, Sweden

    Å Borg

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  1. A Andersson
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Correspondence to A Andersson.

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Andersson, A., Edén, P., Lindgren, D. et al. Gene expression profiling of leukemic cell lines reveals conserved molecular signatures among subtypes with specific genetic aberrations. Leukemia 19, 1042–1050 (2005). https://doi.org/10.1038/sj.leu.2403749

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