Gonzalo Careaga Barja
Introduction. Chronic Myeloid Leukemia (CML) is type of blood cancer that affect the myeloid lineage of leukopoiesis. Most of the cases of CML have the Philadelphia chromosome which is a translocation between chromosome 9 and 22. This abnormal chromosome encodes for BCR-ABL fusion protein which has constitutive tyrosine kinase activity. The breakpoint cluster region-Abelson murine leukemia viral oncogene homolog (BCR-ABL) fusion protein activates many signaling pathway proteins. Among them are: myelocytomatosis (myc), Janus kinase/ signal transducers and activator of transcription (JAK/STAT), rat sarcoma (ras) and phosphoinositide 3-kinase/Akt (PI3K/Akt). In this paper, we will focus on the role of STAT5A and STAT5B in CML pathogenesis. Methods. In vitro experiments were conducted using K562 CML cell line and the accumulation of intracellular reactive oxygen species (ROS) was detected using 2,7-dichlorofluorescin-diacetate (DCFH-DA) probes. Immunoblot analysis of protein expression levels of STAT5 were obtained from K562 CML cells. In another study antisense oligodeoxynucleotides were applied to block STAT5A and STAT5B at the mRNA level, and pRT-PCR was used to determine STAT5 mRNA expressions levels in the cells after oligodeoxynucleotides treatment. Results. STAT5 promotes ROS production in Bcr-Abl+ leukemia cells4. In another study, it was shown that STAT5 promotes Reactive Oxygen Species (ROS) production by repressing expression of two antioxidants: glutaredoxin and catalase1. In addition, STAT5 knockdown was found to suppress CML cell growth and enhanced their apoptosis3. Studies have shown that IM-resistant CML cells show enhanced STAT5 dependence2. Conclusion. Studies have shown that STAT5 overexpression in Philadelphia positive CML cells results in accumulation of ROS. Drug resistant CML cells show enhanced STAT5 dependence.
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