AI Article Synopsis
- The study investigates the role of a receptor tyrosine kinase called RON in acute myeloid leukemia (AML), finding that it is expressed in over half of the patient samples analyzed.
- The short form of RON (sfRON) is particularly significant as it is absent in normal blood cells and interacts with other proteins that contribute to cancer cell survival and proliferation, suggesting unique oncogenic signaling pathways.
- The drug 5-azacytidine can modulate sfRON expression in leukemic cells, and inhibitors targeting cMET/RON have shown potential anti-leukemic effects, indicating they could be a viable treatment option for patients with sfRON-positive AML.
Article Abstract
Several receptor tyrosine kinases (TKs) are involved in the pathogenesis of acute myeloid leukemia (AML). Here, we have assessed the expression of the Recepteur d'Origine Nantais (RON) in leukemic cell lines and samples from AML patients. In a series of 86 AML patients, we show that both the full length and/or the short form (sf) of RON are expressed in 51% and 43% of cases, respectively. Interestingly, sfRON is not expressed in normal CD34+ hematopoietic cells and induces part of its oncogenic signaling through interaction with the Src kinase Lyn. sfRON-mediated signaling in leukemic cells also involves mTORC1, the proapoptotic bcl2-family member, BAD, but not the phosphatidylinositol 3-kinase/Akt pathway. Furthermore, the expression of sfRON was specifically downregulated by 5-azacytidine (AZA). Conversely, AZA could induce the expression of sfRON in sfRON-negative leukemic cells suggesting that the activity of this drug in AML and myelodysplastic syndromes could involve modulation of TKs. cMET/RON inhibitors exhibited an antileukemic activity exclusively in AML samples and cell lines expressing sfRON. These results might support clinical trials evaluating cMET/RON inhibitors in AML patients expressing sfRON.
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| http://dx.doi.org/10.1038/leu.2012.240 | DOI Listing |
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