MicroRNA expression profiling in Imatinib-resistant Chronic Myeloid Leukemia patients without clinically significant ABL1-mutations

Edurne San José-Enériz,María José Calasanz,Xabier Agirre,Amaia Vilas-Zornoza,Vanesa Martin,Lucia Cordeu,José Román-Gómez,Felipe Prósper,Antonio Jiménez-Velasco,Leire Garate,Paula Rodríguez-Otero

doi:10.1186/1476-4598-8-69

Abstract

The development of Imatinib Mesylate (IM), the first specific inhibitor of BCR-ABL1, has had a major impact in patients with Chronic Myeloid Leukemia (CML), establishing IM as the standard therapy for CML. Despite the clinical success obtained with the use of IM, primary resistance to IM and molecular evidence of persistent disease has been observed in 20-25% of IM treated patients. The existence of second generation TK inhibitors, which are effective in patients with IM resistance, makes identification of predictors of resistance to IM an important goal in CML. In this study, we have identified a group of 19 miRNAs that may predict clinical resistance to IM in patients with newly diagnosed CML.

Highlights

The development of Imatinib Mesylate (IM), the first specific inhibitor of BCR-ABL1, has had a major impact in patients with Chronic Myeloid Leukemia (CML) [1]
The existence of second generation TK inhibitors, which are effective in patients with IM resistance, makes identification of predictors of resistance to IM an important goal in CML
With the objective of deciphering a potential miRNA expression signature associated with IM resistance, we analyzed the expression profile of 250 miRNAs by Q-RTPCR using TaqMan methodology (PE Applied Biosystems, Foster City, CA) using bone marrow mononuclear cells from patients with Ph+ CML at diagnoses (n = 8)

Summary

Introduction

The development of Imatinib Mesylate (IM), the first specific inhibitor of BCR-ABL1, has had a major impact in patients with Chronic Myeloid Leukemia (CML) [1]. With the objective of deciphering a potential miRNA expression signature associated with IM resistance, we analyzed the expression profile of 250 miRNAs by Q-RTPCR using TaqMan methodology (PE Applied Biosystems, Foster City, CA) using bone marrow mononuclear cells from patients with Ph+ CML at diagnoses (n = 8). Expression of 250 miRNAs was analyzed using specific primers and TaqMan probe for each miRNA according to the TaqMan MicroRNA Assay Protocol (Applied Biosystems, Foster City, CA).

Results

Conclusion