Combination therapy using TGF-β1 and STI-571 can induce apoptosis in BCR-ABL oncogene-expressing cells

The BCR-ABL oncogene is a tyrosine kinase gene that is over-expressed in CML. It inhibits the TGF-β1 signaling pathway. Due to resistance of cells to the tyrosine kinase inhibitor, STI-571, the combined effect of STI-571 and TGF-β1 on K562 cells was studied in the present research. Results revealed that the TGF-β1 cell signaling pathway, which is activated in K562 cells treated with TGF-β1, activates collective cell signaling pathways involved in survival and apoptosis. It is noteworthy that treating K562 cells with STI-571 triggered apoptotic pathways, accompanied by a reduction in proteins such as Bcl-xL, Bcl-2, p-AKT, p-Stat5, p-FOXO3, and Mcl-1 and an increase in the pro-apoptotic proteins PARP cleavage, and p27, leading to an increase in sub-G1 phase-arrested and Annexin-positive cells. Interestingly, the proliferation behavior of TGF-β1-induced cells was changed with the combination therapy, and STI-571-induced apoptosis was also prompted by this combination. Thus, combination treatment appears to promote sub-G1 cell cycle arrest compared to individually treated cells. Furthermore, it strongly triggered apoptotic signaling. In conclusion, TGF-β1 did not negatively impact the effect of STI-571, based on positive annexin cells, and AKT protein phosphorylation remains effective in apoptosis.

Study of patients diagnosed with Chronic Myelogenous Leukemia treated with STI 571 (Gleevec) in Ecuador

Se considera como principal marcador de la Leucemia Mieloide Crónica (LMC) la translocación t(9;22) o cromosoma Ph que ocurre en un 90 -95% de pacientes con LMC. Uno de los tratamientos más efectivos es el Gleevec cuyo blanco son las células Ph positivo. Una ventaja de esta nueva droga es la discriminación entre células normales y anormales, y la inducción de apoptosis. Se estudiaron 31 pacientes: 13 en fase crónica, 12 en fase acelerada y 6 en crisis blástica a lo largo de 1 año. Se obtuvo remisión hematológica en todos los casos de fase crónica, pero en los pacientes en fase acelerada y crisis blástica respondieron aproximadamente el 50%. La remisión cito genética ocurrió en un 79% de fase crónica y varía de un 17 a 32 % en fase acelerada y crisis blástica. No existió remisión molecular en ningún paciente. El análisis genético es una buena herramienta para determinar la efectividad del tratamiento y seguimiento de los casos de leucemia.