Activation of signaling pathways in models of t(6;9)-acute myeloid leukemia

• DOI: 10.1007/s00277-022-04905-9
• Publication Date: 2022-08-08T18:02:43Z
• Authors: Claudia Chiriches; Dilawar Khan; Maria Wieske; Nathalie Guillen; Michal Rokicki; Carol Guy; Marieangela Wilson; Kate J. Heesom; Oliver Gerhard Ot...; Martin Ruthardt
• Keywords: ETV6; Hematology; ABL

Patients within the WHO-subgroup of t(6;9)-positive acute myeloid leukemia (AML) differ from other AML subgroups as they are characterised by younger age and a grim prognosis. Leukemic transformation can often be attributed to single chromosomal aberrations encoding oncogenes, in case t(6;9)-AML fusion protein DEK-CAN (also called DEK-NUP214). As being rare disease there is urgent need for models t(6;9)-AML. The only cell line derived patient currently available FKH1. By using phospho-proteomics on FKH1 cells, we found strongly activated ABL1 kinase. Further investigation revealed presence ETV6-ABL1. This finding renders necessary determine DEK-CAN- ETV6-ABL1-related features when done ETV6-ABL1 activity responsive imatinib. Nevertheless, provided evidence that both SFK mTOR activation DEK-CAN-related were also t(6;9) DEK-CAN-positive models. STAT5 previously shown strong regulated In conclusion, cells still represent model could serve ETV6-ABL1-positive if these leukemia-inducing oncogenes adequately considered.Taken together, all our results provide clear novel specific interdependencies between cancer signaling pathways which will influence design therapeutic strategies better address complexity signaling.