Details

Autor(en) / Beteiligte

• Wilhelm, Brian T.
• Briau, Mathieu
• Austin, Pamela
• Faubert, Amélie
• Boucher, Geneviève
• Chagnon, Pierre
• Hope, Kristin
• Girard, Simon
• Mayotte, Nadine
• Landry, Josette-Renee
• Hébert, Josée
• Sauvageau, Guy

Titel

RNA-seq analysis of 2 closely related leukemia clones that differ in their self-renewal capacity

Ist Teil von

• Blood, 2011-01, Vol.117 (2), p.e27-e38

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2011

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• The molecular mechanisms regulating self-renewal of leukemia stem cells remain poorly understood. Here we report the generation of 2 closely related leukemias created through the retroviral overexpression of Meis1 and Hoxa9. Despite their apparent common origin, these clonal leukemias exhibit enormous differences in stem cell frequency (from 1 in 1.4, FLA2; to 1 in 347, FLB1), suggesting that one of these leukemias undergoes nearly unlimited self-renewal divisions. Using next-generation RNA-sequencing, we characterized the transcriptomes of these phenotypically similar, but biologically distinct, leukemias, identifying hundreds of differentially expressed genes and a large number of structural differences (eg, alternative splicing and promoter usage). Focusing on ligand-receptor pairs, we observed high expression levels of Sdf1-Cxcr4; Jagged2-Notch2/1; Osm-Gp130; Scf-cKit; and Bmp15-Tgfb1/2. Interestingly, the integrin beta 2-like gene (Itgb2l) is both highly expressed and differentially expressed between our 2 leukemias (∼ 14-fold higher in FLA2 than FLB1). In addition, gene ontology analysis indicated G-protein-coupled receptor had a much higher proportion of differential expression (22%) compared with other classes (∼ 5%), suggesting a potential role regulating subtle changes in cellular behavior. These results provide the first comprehensive transcriptome analysis of a leukemia stem cell and document an unexpected level of transcriptome variation between phenotypically similar leukemic cells.