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


  • Obumneme B. Ezeanosike Departments of Paediatrics and Pharmacology Federal Teaching Hospital Abakaliki/Ebonyi State University Abakaliki
  • Onyenmechi J. Afonne Department of Pharmacology, Nnamdi Azikiwe University, Nnewi, Anambra State, Nigeria



Chronic myeloid leukaemia, Imatinib mesylate, Micro RNA, Prognostic markers


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. 

Author Biography

Obumneme B. Ezeanosike, Departments of Paediatrics and Pharmacology Federal Teaching Hospital Abakaliki/Ebonyi State University Abakaliki




Ostendorf BN. BCR-ABL Mutation-Guided Therapy for CML Blast Crisis: A Case Report. Biomark Insights. 2015;10(3):25-8.

Jamieson CH. Chronic myeloid leukemia stem cells. ASH Education Program Book. 2008;2008(1):436-42.

Jemal A. Cancer statistics. CA Cancer J Clin. 2010;60(5):277-300.

Rowley JD. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973;243(5405):290-3.

Mandanas RA. Role of p21 RAS in p210 bcr-abl transformation of murine myeloid cells. Blood. 1993;82(6):1838-47.

Raitano AB. The Bcr-Abl leukemia oncogene activates Jun kinase and requires Jun for transformation. Proc Natl Acad Sci USA. 1995;92(25):11746-50.

Shuai K. Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia. Oncogene. 1996;13(2):247-54.

Saglio G, Baccarani M. First-line therapy for chronic myeloid leukemia: new horizons and an update. Clin Lymphoma Myeloma Leuk. 2010;10(3):169-76.

Apperley JF. Part I: mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol. 2007;8(11):1018-29.

Apperley JF. Part II: management of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol. 2007;8(12):1116-28.

Ramkissoon SH. Hematopoietic-specific microRNA expression in human cells. Leuk Res. 2006;30(5):643-7.

Agirre X. Down-regulation of hsa-miR-10a in chronic myeloid leukemia CD34+ cells increases USF2-mediated cell growth. Mol Cancer Res. 2008;6(12):1830-40.

La Rosee P and Hochhaus A, Resistance to imatinib in chronic myelogenous leukemia: mechanisms and clinical implications. Curr Hematol Malig Rep. 2008;3(2):72-9.

San Jose-Eneriz E. MicroRNA expression profiling in Imatinib-resistant Chronic Myeloid Leukemia patients without clinically significant ABL1-mutations. Mol Cancer. 2009;8:69.

Lu J. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834-8.

Yu Y. Targeting microRNA-30a-mediated autophagy enhances imatinib activity against human chronic myeloid leukemia cells. Leukemia. 2012;26(8):1752-60.

Marcucci G, Maharry K, Radmacher MD, Mrózek K, Vukosavljevic T, Paschka P, et al. Prognostic significance of, and gene and microRNA expression signatures associated with, CEBPA mutations in cytogenetically normal acute myeloid leukemia with high-risk molecular features: a Cancer and Leukemia Group B Study. J Clinic Oncol. 2008;26(31):5078-87.

Nashed AL, Rao KW and Gulley ML. Clinical applications of BCR-ABL molecular testing in acute leukemia. J Mol Diagn. 2003;5(2):63-72.

Chomczynski P and Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: twenty-something years on. Nat Protoc. 2006;1(2):581-5.

Chomczynski P and Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162(1):156-9.

Benes V and Castoldi M. Expression profiling of microRNA using real-time quantitative PCR, how to use it and what is available. Methods. 2010;50(4):244-9.

Baccarani M. Chronic myeloid leukemia: an update of concepts and management recommendations of European Leukemia Net J Clin Oncol. 2009;27(35):6041-51.

Jennings LJ. Detection and Quantification of BCR-ABL1 Fusion Transcripts by Droplet Digital PCR. J Molec Diagnost. 2014;16(2):174-9.

Balasubramanian P. International reporting scale of BCR-ABL1 fusion transcript in chronic myeloid leukemia: first report from India. Acta Haematol. 2012;127(3):135-42.

Asuragen Inc. BCR-ABL Testing, BCR-ABL Test, BCR-ABL International Scale. 2016. Available from:

Zhang Y and Rowley JD. Chronic myeloid leukemia: current perspectives. Clin Lab Med. 2011;31(4):687-98.

Flamant S. Micro-RNA response to imatinib mesylate in patients with chronic myeloid leukemia. Haematologica. 2010;95(8):1325-33.

Machova Polakova K. Expression patterns of microRNAs associated with CML phases and their disease related targets. Mol Cancer. 2011;10:41.






Original Research Articles