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Additional file 5. pathway_components. Abstract of the WNT and BCR signaling pathway and the components.

Additional file 3. supplement figures. Heatmaps of the top-100 up- and downregulated genes of the biological triplicates.

Additional file 1. FACS plots. Plots of apoptotic (Annexin V FITC+ and Propidium iodide-) and necrotic cells (Annexin V FITC+ and Propidium iodide+) detected by flow cytometry analysis at 72h of pro-B ALL cell lines RS4;11 and SEM exposed with AraC, DEX and IDEL and two drugs combined (AraC+IDEL, DEX+IDEL).

Additional file 2. supplement tables. Comparison of the differential expression analysis of RS4;11 and SEM exposed with AraC, DEX and IDEL and two drugs combined (AraC+IDEL, DEX+IDEL) for 72 h.

Additional file 6. pw_ranking_Idel. Pathway ranking of pathways with components mTOR, BTK, AKT, and PI3K.

Background The introduction of combined conventional cytostatics and pathway-specific inhibitors has opened new treatment options for several cancer types including hematologic neoplasia such as leukaemias. As the detailed understanding of the combination-induced molecular effects is often lacking, the identification of combination-induced molecular mechanisms bears significant value for the further development of interventional approaches. Methods Combined application of conventional cytostatic agents (cytarabine and dexamethasone) with the PI3K-inhibitor Idelalisib was analysed on cell-biologic parameters in two acute pro-B lymphoblastic leukaemia (B-ALL) cell lines. In particular, for comparative characterisation of the molecular signatures induced by the combined and mono application, whole transcriptome sequencing was performed. Emphasis was placed on pathways and genes exclusively regulated by drug combinations. Results Idelalisib + cytostatics combinations changed pathway activation for, e.g., “Retinoblastoma in cancer”, “TGF-b signalling”, “Cell cycle” and “DNA-damage response” to a greater extent than the two cytostatics alone. Analyses of the top-20 regulated genes revealed that both combinations induce characteristic gene expression changes. Conclusion A specific set of genes was exclusively deregulated by the drug combinations, matching the combination-specific anti-proliferative cell-biologic effects. The addition of Idelalisib suggests minor synergistic effects which are rather to be classified as additive.