Contribution of Protein Tyrosine Phosphateses to the Ontogeny and Progression of Chronic Myeloid Leukemia

摘要

The JAK and STAT families of signal transduction molecules play a critical role in the pathogenesis of chronic myeloid leukemias (CML). Inappropriate STAT1 and STAT5 activation have been observed in the Philadelphia chromosome-positive CML cell lines K562 and BV17, yet low levels of JAK1 tyrosine phosphorylation were observed suggesting that BCR/Abl directly tyrosine phosphorylates and activates STATs. The protein tyrosine phosphatases TC-PTP and PTP1B are negative regulators of JAK/STAT signaling molecules and it is possible that these two PTPs could impede the ability of CML cells to survive and proliferate in response to p210 BCR-Abl. We examined the role of TC- PTP and PTP1b in contributing to the CML phenotype and found that in some CML cell lines the levels of TC-PTP and PTP1b is increased suggesting that they may be the potential caused of the reduced phosphorylation of the JAK kinases in CML.