EJMS

Abstract

Background: Acute myeloid leukemia (AML) is a clonal, malignant disease of hematopoietic tissues that is characterized by accumulation of abnormal blast cells, principally in the marrow, and impaired production of normal blood cells. MicroRNAs (miRNAs) are short non-coding RNAs of ~ 21 to 23 nucleotides in length that post-transcriptionally regulate mRNA expression. High-throughput methodologies have shown deregulated miRNA expression in an increasing number of human cancers including colon, breast, lung, thyroid, cervical, ovarian and pancreatic cancers. MiRNA expression patterns have been found to distinguish tumors of different developmental origin, better even than traditional mRNA expression profiling. MiR-92a is transcribed from miR-17-92 locus that encode the polycistronic precursor containing seven microRNAs:miR-17-5p, miR-17-3p, miR-18, miR-19a, miR-20, miR-19b andmiR-92a, and the human microRNA cluster miR-17-92 is amplified and/or overexpressed in cells of several cancer such as malignant lymphoma, lung cancer, thyroid cancer, and hepatocellular carcinoma. Aim: To assess plasma level of micro-RNA 92a in adult acute myeloid leukemia and to correlate it with prognostic factors and therapeutic response. Patients and Methods: This study was carried out on twenty five subjects with AML admitted to hematology unit in Alexandria University Hospital as patients group as well as twenty five healthy subjects as control group. Conventional cytogenetics and FLT3/ITD gene mutation using PCR were done to patients group while measurement of plasma level of miR-92a using TaqMan quantitative RT-PCR and miR-638 as standardization was done to both groups. Therapeutic response was assessed in patients group by doing bone marrow aspirate at day 28 of induction chemotherapy. Results: The ratio or relative quantitation (RQ) of plasma miR-92a to miR-638 in patient group had a mean of 0.239±0.286 while in control group it had a mean of 0.969±0.490 that confirmed statistical significance (p =0.000*). Also there was significant negative correlation between RQ of miR-92a and white blood count in patient group (p = 0.001*). Patients who achieved response (complete or partial remission) after induction chemotherapy had a mean RQ of miR-92a higher than non-responder (0.28 ± 0.30 versus 0.073± 0.077 respectively) with statistical significance (P=0.048). As regard to cytogenetic, favorable risk cytogenetic in 9cases had mean RQ of miR-92a = 0.233±0.393 that was comparable to intermediate risk cytogenetic in 15 cases, that had a mean RQ = 0.258± 0.217. While poor risk cytogenetic in one case {-5} had a mean RQ=0.001 which is significantly lower than both favourable and intermediate risk cytogenetic (P=0.050). There was no significant correlation between RQ of miR-92a and FLT3/ITD and bone marrow blasts on admission. Summary/ Conclusions: plasma level of miR-92a is decreased in newly diagnosed AML patients than normal subjects, and it was related to high white blood count. If we correlate these findings with other studies that suggest that microRNAs are packaged inside exosomes that are secreted from cells to be delivered to other cells and function in a new location. Thus, it might be possible that blast cells specifically take in the exosomes that contain miR-92a and, as a result, miR-92a decreases from the plasma. This may justify the possibility of its usage in the prognosis of AML. Our data suggest the potential importance of the microRNA92a as non-invasive cancer biomarkers helping in diagnosis, clinical prediction and therapeutic response.