| First Author | Demirel Ö | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 7 | Pages | e0180401 |
| PubMed ID | 28753604 | Mgi Jnum | J:245164 |
| Mgi Id | MGI:5915400 | Doi | 10.1371/journal.pone.0180401 |
| Citation | Demirel O, et al. (2017) SOCS1 function in BCR-ABL mediated myeloproliferative disease is dependent on the cytokine environment. PLoS One 12(7):e0180401 |
| abstractText | Treatment with tyrosine kinase inhibitors is the standard of care for Philadelphia chromosome positive leukemias. However the eradication of leukemia initiating cells remains a challenge. Circumstantial evidence suggests that the cytokine microenvironment may play a role in BCR-ABL mediated leukemogenesis and in imatinib resistance. Gene expression analyses of BCR-ABL positive ALL long-term cultured cells revealed strong reduction of SOCS mRNA expression after imatinib treatment, thereby demonstrating a strong inhibition of cytokine signaling. In this study we employed SOCS1-a strong inhibitor of cytokine signaling-as a tool to terminate external cytokine signals in BCR-ABL transformed cells in vitro and in vivo. In colony formation assays with primary bone marrow cells, expression of SOCS1 decreased colony numbers under pro-proliferative cytokines, while it conferred growth resistance to anti-proliferative cytokines. Importantly, co-expression of SOCS1 with BCR-ABL led to the development of a MPD phenotype with a prolonged disease latency compared to BCR-ABL alone in a murine bone marrow transplantation model. Interestingly, SOCS1 co-expression protected 20% of mice from MPD development. In summary, we conclude that under pro-proliferative cytokine stimulation at the onset of myeloproliferative diseases SOCS1 acts as a tumor suppressor, while under anti-proliferative conditions it exerts oncogenic function. Therefore SOCS1 can promote opposing functions depending on the cytokine environment. |
