Publication:

Prognostic significance of micro RNA 150 marker in BCR-ABL positive chronic myeloid leukaemia patients on imatinib mesylate

Background Micro-RNAs control gene expression by destabilizing targeted transcripts and inhibiting their translation. In chronic myeloid leukaemia (CML), abnormal expressions of miRNAs have been described. The current treatment for newly diagnosed cases of CML is imatinib mesylate which produces rapid haematological responses. It is currently impossible to predict whether a patient will develop resistance to imatinib mesylate. This makes identification of predictors of resistance to imatinib an important goal in management of patients with CML. MicroRNA expression patterns can be used to predict outcome which can be remission or relapse. This study therefore, was set to assess the possible use of microRNA 150 for prognostication.

Methods Fifty peripheral blood samples previously collected from CML patients who were being treated with imatinib mesylate and stored in the refrigerator at +4°C were analyzed for the expression of microRNAs 150. Total RNA was extracted from guanidium isothiocynate (GITC) lysate of the blood samples using RNeasy mini spin column. The total RNA was converted to complimentary DNA by random hexamer priming using Murine Moloney Leukaemia Virus Reverse Transcriptase. Real time Multiplex PCR was used for detecting Breakpoint Cluster Region-Abelson Murine Leukaemia (BCR-ABL) transcript type.

Results The patients’ samples showed an expression of miRNA-150. Correlation of BCR-ABL ratio with miRNA-150 was done and the Spearman correlation coefficient (Rho) between BCR-ABL1 and miRNA-150 was 0.442 (p = 0.001; CI = 0.18-0.65) showing that there was a positive correlation between BCR-ABL1 and miRNA-150. The coefficient of determination was 20% (CI = 3-42%), which implies that about 20% of BCR-ABL1 ratio could be accounted for by the miRNA-150 values.

Conclusions Therefore, once patients who are on imatinib achieve molecular remission of the CML, the miRNA-150 can be useful in predicting outcome which could be relapse or complete molecular remission but is weak at diagnosis in predicting such outcome.