Differential gene expression analysis by RNA-seq reveals the importance of actin cytoskeletal proteins in leukemia cells
- Published
- Accepted
- Subject Areas
- Molecular Biology, Hematology
- Keywords
- leukemia cells, RNA-seq, cell differentiation, HMBA-resistant, Wiskott-Aldrich syndrome, Bruton's tyrosine kinase
- Copyright
- © 2017 Fernández-Calleja et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2017. Differential gene expression analysis by RNA-seq reveals the importance of actin cytoskeletal proteins in leukemia cells. PeerJ Preprints 5:e2731v1 https://doi.org/10.7287/peerj.preprints.2731v1
Abstract
Development of drug resistance limits the effectiveness of anticancer treatments. Understanding the molecular mechanisms triggering this event in tumor cells may lead to improved therapeutic strategies. Here we used RNA-seq to compare the transcriptomes of an erythroleukemia progenitor cell line (MEL-DS19) and a derived cell line with induced resistance to differentiation (MEL-R). RNA-seq analysis identified a total of 596 genes that were differentially expressed by more than two-fold, of which 486 genes were up-regulated in MEL-DS19 cells and 110 up-regulated in MEL-R cells. These observations revealed that the number of genes expressed in the parental cell line decreased as the cells acquired the resistant phenotype. Clustering analysis of a group of genes showing the highest differential expression allowed identification of a sub-group among genes up-regulated in MEL cells. These genes are related with the organization of the actin cytoskeleton network. Moreover, the majority of these genes are preferentially expressed in the hematopoietic lineage and at least three of them, Was (Wiskott Aldrich syndrome), Btk (Bruton tyrosine kinase) and Rac2, when mutated in humans, give rise to severe hematopoietic deficiencies. Among the group of genes that were up-regulated in MEL-R cells, a significant percentage (16%) corresponded to genes coding for histone proteins, both canonical and variants. A potential implication of these results on the blockade of differentiation in resistant cells is discussed.
Author Comment
This is a submission to PeerJ for review.
Supplemental Information
Actin expression in MEL and MEL-R
Raw data for Figure 8
Control for sample loading with tubulin
Raw data for Figure 8
