engleski

Signaling pathways in human acute myeloid leukemia

The aim of our research was to determine phosphorylation status of leukemic blasts by flow cytometry. In this study, we stained cells with anti-AKT (pT308), anti-ERK1/2 (pT202/pY204), and anti-p38 MAPK (pT180/pY182) monoclonal antibodies. In addition, we stained cells with anti-CD45 and/or anti-CD34 to gate only blasts in our samples. Kolmogorov-Smirnov statistical test was used to compare expression of phosphorylated molecules to negative isotype control staining. D value greater than 0.2 (D > 0.2) was considered positive. We found Akt phosphorylation/ activation in 30/48 (62.5%), ERK1/2 in 25/48 (52.1%), and p38 MAPK in 18/48 (37.5%) AML samples (in concordance with results of other AML phosphorylation studies). Interestingly, of these 18 p38 MAPK positive cases, 16 (88.8%) were also Akt positive. Statistical analysis revealed significant correlation (P ¼ 0.0001 ; r ¼ 0.55) between Akt and p38 phosphorylation, and chi-square test showed significantly higher frequency of AKT activation in p38 phosphorylated samples (P ¼ 0.009). In conclusion, signal transduction pathways PI3K/Akt and MAPK are dysregulated in human AML. Activation of p38 accompanied by Akt activation could indicate possible interactions and crosstalk between two signaling cascades. However, this hypothesis remains to be elucidated by further experiments.

acute myeloid leukemia; signaling pathways

nije evidentirano