CAMKIIg, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease.

GONZALEZ MS; DE BRASI CD; FERRI CA; BENGIÓ R; BIANCHINI M; LARRIPA IB

LEUKEMIA AND LYMPHOMA

TAYLOR & FRANCIS LTD

Lugar: Londres; Año: 2014 vol. 55 p. 2101 - 2108

1042-8194

Chronic Myeloid Leukemia (CML) patients can develop resistance to tirosin kinase inhibitors (TKI) therapy, which is mainly attributable to the presence of point mutations in the tirosine kinase domain of BCR-ABL1. In order to examine suitable markers to monitor treatment efficacy, we investigated transcript expression profiles of genes known to be involved in myeloid cell proliferation, such as CAMKIIγ and KI67, and in protein stability and ultimately for cell survival under physiological and stress conditions, such as heat shock proteins HSP70 and HSP90. We studied 101 CML patients in different stages of disease and responses to TKI treatment. The results of qPCR analyses showed that the expression level of CAMKIIγ, KI67, HSP70 and HSP90 genes were upregulated in patients at diagnosis and in cases with signs of treatment resistance both in chronic phase and advanced phases (accelerated and blastic phase) respect to chronic phase in remission and healthy donors.When only 56 resistant cases divided in 31 with mutations (MT) and 25 without mutations (WT) in the BCR-ABL1 tirosine kinase domain were considered, the transcript expression profile showed an unexpected significant increase in CAMKIIγ and HSP70, and a significant decrease in HSP90 in MT versus WT cases. This differential transcript expression prompt us to design an expression score LOG(CAMKIIγ x HSP70 / HSP90), which can be used to provide a rapid screening to discriminate the presence or absence of mutations in resistant patients and to monitor TKI treatment efficacy in CML patients.