الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
CLL is an indolent B cell lymphoproliferative disease characterized by clonal proliferation and the build-up of mature CD5+CD23+ B cells in the bone marrow, lymph nodes, spleen, and blood. The initial and most frequent laboratory abnormality associated with CLL is lymphocytosis. The primary investigation in CLL diagnosis is a peripheral blood smear that reveal an absolute clonal B lymphocyte count of more than 5000/mcL maintained for at least three months. MicroRNAs (miRs) are a group of small, non-coding RNAs that control target messenger RNA expression at the post-transcriptional level. The molecular effects of dysregulated expression of microRNA in CLL have drawn attention recently. Important transcription factors, such as signal transducer and activator of transcription 3 (STAT3) and hypoxia inducible factor 1 alpha subunit (HIF1A), are regulated by both miR-20b-5p and miR-92a-3p.
The present study aimed at evaluating the expression levels of MicroRNA- 20b-5p and MicroRNA- 92a-3p in patients with chronic lymphocytic leukemia and their relation to disease characteristics and other prognostic factors.
The current work was conducted on 50 subjects divided on to two groups. Patients group which includes 40 adult chronic lymphocytic leukemia patients and 10 healthy age and sex matched candidates as a control group.
All subjects enrolled in the study signed an informed written consent before enrollment in the study.
Full history taking, thorough clinical examination, CBC, immunophenotyping , liver and renal functions, β2 microglobulin, uric acid and LDH level measurement were done to all cases.
Quantitative Real time PCR was performed for detection of miR- 20b-5p and miR- 92a-3p expression using mercury LNATM SYBER Green PCR kit, RNA was extracted from peripheral blood mononuclear cells, Reverse transcribed then amplified by real-time PCR amplification with LNA-enhanced primers.
The data collected were statistically analyzed and used to formulate equations from different variables.
The results of the current study revealed the following:
miR20b-5p and miR92a-3p expression in patients were statistically significant higher than in control groups. According to the ROC curve, the expression of miR-20b-5p and miR-92a-3p may be employed as a substitute screening biomarker for CLL diagnosis.
Summary, Conclusion and Recommendations
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A negative correlation was detected between the miR-20b-5p and miR-92a-3p expression and serum β2microglobulin values of patients with p values of 0.014 and <0.001 respectively.
A statistically significant positive correlation was found between the miR-20b-5p and miR-92a-3p expression and percentage of smudge cells of patients with p values of 0.027 and 0.001 respectively.
There was a statistically significant higher miR-92a-3p expression in patients showing no expression of CD38 when compared to patients who express CD38 with p value of 0.030.
There was a statistically significant higher miR-92a-3p expression in patient without deletion 17p when compared to patients with 17p deletion. (p=0.028).
6.2. Conclusions
The present study highlighted the role of miR-20b-5p & miR-92a-3p in CLL patients:
Low miR-20b-5p & miR-92a-3p expression are associated with some other bad prognostic markers in CLL including advanced Modified-Rai stage at diagnosis, higher β2 microglobulin levels, 17p deletion as well as positive CD38 and ZAP-70 expression.
High miR-20b-5p & miR-92a-3p expression are associated with increased smudge cell percentage.
High miR-20b-5p & miR-92a-3p expression represent a novel molecular biomarker of favorable prognosis in CLL.
miR-20b-5p & miR-92a-3p are highly expressed in CLL patients than the control group which may suggest that expression of miR-20b-5p and miR-92a-3p may be utilized as a stand-in screening biomarker for CLL diagnosis.
6.3. Recommendations
Variable degree of miR-20b-5p & miR-92a-3p expression in CLL patients vs. control should be an area of study in a larger cohort of patients to assess its sensitivity & specificity as a disease diagnostic modality.
miR-20b-5p & miR-92a-3p expression should be further studied as a potential diagnostic marker with clinically applicable cut off values with an acceptable test specificity & sensitivity for both microRNAs in a disease of variation and more diverse courses and wide range of treatment options and different survival rates.
Further larger prospective studies are recommended to determine the effect of miR-20b-5p & miR-92a-3p positivity on overall survival as well as progression free survival in order to gain a wider perspective of the miR-20b-5p & miR-92a-3p prognostic role of CLL.