Down-regulation of miR-181c in imatinib-resistant chronic myeloid leukemia

Neda Mosakhani,Sakari Knuutila,Satu Mustjoki

doi:10.1186/1755-8166-6-27

Abstract

The association of microRNA alterations with progression and treatment outcome has been revealed in different types of cancers. To find miRNAs involved in imatinib response we performed miRNA microarray followed by RT-qPCR verification of 9 available diagnostic bone marrow core biopsies from 9 CML patients including 4 imatinib-resistant and 5 imatinib-responder patients. Only one differentially expressed miRNA, miR-181c, was found when the imatinib-resistant group was compared with imatinib-responders. Significant down-regulation of miR-181c in imatinib-resistant versus imatinib-responders was confirmed by qRT-PCR. Some miR-181c target genes such as PBX3, HSP90B1, NMT2 and RAD21 have been associated with drug response.

Highlights

The association of microRNA alterations with progression and treatment outcome has been revealed in different types of cancers
In most of the patients, the ABL tyrosine kinase of the fusion protein is effectively inhibited by the tyrosine kinase inhibitors (TKIs), but some patients are resistant to TKI therapy
To understand which miRNAs are associated with the TKI therapy response, we performed miRNA microarray in 9 bone marrow core biopsies derived from 9 Chronic myeloid leukemia (CML) patients at diagnosis including 5 imatinib-responder and 4 imatinib-resistant patients

Summary

Introduction

The association of microRNA alterations with progression and treatment outcome has been revealed in different types of cancers. Whereas the BCR-ABL fusion drives the initial chronic phase of the disease, the progression of CML involves additional genomic changes which make leukemia cells resistant to TKI therapy and independent of BCR-ABL. To understand which miRNAs are associated with the TKI therapy response, we performed miRNA microarray in 9 bone marrow core biopsies derived from 9 CML patients at diagnosis including 5 imatinib-responder and 4 imatinib-resistant patients.

Results

Conclusion