الفهرس 
ACUTE MYELOID LEUKEMIAOnly 14 pages are availabe for public view
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Abstract
Acute myeloid leukemia is the most frequent hematological malignancy in adults. Specific molecular markers have been identified as having significant prognostic value, and are currently used to tailor the therapeutic strategies.
microRNAs are small non-coding RNAs of 19–24 nucleotides in length that regulate gene expression by post-transcriptional mechanism. miR-181b deregulation has been associated with leukemogenesis and may have a prognostic value in detection of the therapeutic response of AML.
This study was carried out on 40 newly diagnosed AML patients attending Hematology Oncology Unit of Ain -Shams University Hospitals. Their mean age was 40.2 ± 17.7 years with male to female ratio of 1.3:1. Twenty healthy volunteers were taken as control group. Their mean age was 38.8 ± 15.2 years, with male to female ratio of 1:1.
Diagnosis of AML was based on full history, clinical examination, complete blood picture, the presence of >20% blast cells in the BM film together with myelperoxidase positive staining, immunophenotyping by FCM, and FISH analysis.
Detection and relative quantification of miR-181b expression levels, was performed on 60 PB (or BM) samples using stem loop RT- PCR. Regarding miR-181b expression level, a statistically significant difference was found between AML patients and control group denoting significantly higher miR-181b expression levels in AML patients compared to controls (P = 0.013).
Follow up of the AML patients for 28 days was done to identify their therapeutic response. Out of the 40 patients, 27/40 (67.5%) achieved CR, while 13/40 (32.5%) failed to achieve remission. Patients were subsequently subdivided into two groups; CR and IR/NR, both of which were compared, as regards the standard prognostic factors in AML. A highly significant statistical difference was revealed regarding FISH analysis (P=0.001), as 12/13 (92.3%) of the patients who had favorable cytogenetics achieved CR and only 1/13 (7.7%) failed to achieve CR. However, no statistically significant association was detected as regards demographic data or other standard prognostic factors with therapeutic response.
The AML patients were further subdivided into two groups according to the cut-off of miR-181b determined by ROC curve; a group of patients with miRNA ³ 6.86 and a group of patients with miRNA <6.86. The two groups were compared as regards standard prognostic factors and therapeutic response of AML patients. A statistically significant difference was detected between both groups as regards cytogenetics (FISH analysis) (P= 0.027). All patients with unfavorable cytogenetics 5/5 (100%) expressed miR-181 b levels < 6.86.Whereas patients with favorable cytogenetics, 12/13 (92.3%) of them showed miR-181b levels ³ 6.86 and only 1/13 (7.6 %) showed a level < 6.86. However, no statistically significant difference was observed between both groups as regards other demographic, clinical, and laboratory data.
Regarding relation of miR-181b to therapeutic response, all of the patients with miR-181b expression level ³ 6.86 succeeded to achieve CR, while all of the patients with miR-181b expression level < 6.86 failed to achieve CR. A highly significant statistical association was detected between therapeutic response and miR-181b (p= 0.000), denoting the prognostic value of miR-181b.