International Journal of Medical Laboratory

Background and Aims: Chronic lymphocytic leukemia (CLL) is the most common adult human leukemia. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Research has shown that in CLL, microRNAs can have function as oncogenes or tumor suppressors. Some studies demonstrated that the expression of microRNA-93 (miR-93) and microRNA-330 (miR-330) have been changed in several cancers, including lung, prostate, and colon cancer. We aimed to elucidate the changes in miR-93 and miR-330 expression in CLL patients in comparison with controls.
Materials and Methods: In this case-control study, the expression levels of miR-93 and miR-330 was evaluated in 30 CLL patients who had referred to Omid Hospital, Isfahan, Iran, and 30 controls in peripheral blood mononuclear cells using reverse transcription quantitative PCR (RT-qPCR).
Results: The expression of miR-93 and miR-330 were found to significantly increase in CLL patients compared with controls (p<0.0001).
Conclusions: The findings indicated that miR-93 and miR-330 are probably the novel potential biomarker for early diagnosis of CLL, at least in Iranian patients. However, for a decisive result, further investigations are warranted. 

Epigenetic changes play an essential role in cancer pathogenesis. It has been established by next-generation sequencing that more than 50% of the human cancers carry mutations in mechanisms involved in the organization of the chromatin and epigenetic regulations. DNA methylation is among the most common epigenetic changes in leukemia. In contrast to DNA mutations which are passively inherited from DNA replication, epimutations, for example, the hypermethylation and epigenetic silencing of tumor suppressor genes, must be actively maintained because of being reversible. Actually, the reversibility of epimutations by small-molecule inhibitors provides the basis for the use of such inhibitors in new cancer therapy strategies. However, DNA methylation mechanism and its role in leukemia are not fully understood; there are some serious concerns about the use of these drugs. In this study, we will review the mechanisms of DNA methylation and the genes that are methylated in leukemia. Moreover, new interesting findings of the epigenetic changes causeed by adult T-cell leukemia/lymphoma have been fully discussed.

Background and Aims: Previous investigations have revealed that microRNAs (miRNAs) can function as oncogenes or tumor suppressors in chronic lymphocytic leukemia (CLL) and that the expression of miRNAs, such as miR-485-3p changes in several illnesses. This study was designed to determine the expression level of miR-485-3p and its target FOXD3 in CLL patients and controls to identify if this miRNA has the potential to be considered as a biomarker in CLL.
Materials and Methods: A total of 35 CLL patients and the same number of controls were recruited. Following total RNA extraction and cDNA synthesis, quantitative analysis was performed by real-time polymerase chain reaction (PCR) using the SYBR Green PCR Master Mix to determine the expression level of miR-485-3p and its target. Moreover, in silico molecular enrichment analysis was conducted on targetome of miR-485-3p.
Results: It was observed that the expression level of miR-485-3p was upregulated in CLL patients compared with controls (p<0.009). However, the expression profile of miR-485-3p’s target (FOXD3) was significantly downregulated in patients in comparison with the control group (p<0.02).
Conclusions: Based on the results, miR-485-3p could be a novel biomarker to diagnose CLL and to design novel CLL control strategies by targeting FOXD3.

Background and Aims: DNA methyltransferase3A (DNMT3A) is necessary for the adjustment of gene expression, and the mutations in the DNMT3A gene are reported in a variety of leukemia cases. DNMT3A mutations are during cancer progression and cause poor prognosis in many leukemias. Thus, this gene can be a target for new treatments. This study aimed to examine the distribution of DNMT3A mutations in Iranian acute leukemia patients.
Materials and Methods: In this study, diagnostic samples from 45 patients with de novo acute leukemia, including 22 acute myeloid leukemia (AML) patients, and 23 acute leukemia lymphoblastic (ALL) patients were screened, from April 2017 to March 2018 for the incidence of DNMT3A mutations by polymerase chain reaction and direct sequencing.
Results: A total of 2 (9.1%) AML cases and 1 (4.34%) ALL cases were found to have the DNMT3A R882H mutation. It was found that a total of 22.7% and 21.7% of patients with AML and ALL had polymorphism rs368516543, respectively. DNMT3A mutations were considerably associated with higher age in AML patients.
Conclusions: The findings suggest that the DNMT3A mutations are probably a new biomarker in the early examination and treatment of acute leukemia, even though further studies are needed.