Expression Profiles of miR-93 and miR-330 in Iranian Patients with Chronic Lymphocytic Leukemia

2019 ◽  
Author(s):  
Behnaz Nateghi ◽  
Elahe Shams ◽  
Parisa Behshood ◽  
Sima Fathullahzadeh ◽  
Mansoor Salehi
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Lymphocytic Leukemia ◽  
Human Leukemia ◽  
The Novel ◽  
Peripheral Blood Mononuclear ◽  
Potential Biomarker ◽  
Reverse Transcription Quantitative Pcr ◽  
Iranian Patients

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

scholarly journals Circulating miR-95 Is a Potential Biomarker of Chronic Lymphocytic Leukemia

2019 ◽  
Author(s):  
Behnaz Nateghi ◽  
Parisa Behshood ◽  
Sima Fathullahzadeh ◽  
Omid Mardanshah
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Real Time ◽  
Real Time Pcr ◽  
Mononuclear Cells ◽  
Lymphocytic Leukemia ◽  
Pathway Enrichment Analysis ◽  
Healthy Controls ◽  
Quantitative Real Time Pcr ◽  
Peripheral Blood Mononuclear ◽  
Potential Biomarker

Background: MicroRNAs (miRNAs) have crucial roles in cellular and molecular processes related to different malignancies including chronic lymphocytic leukemia (CLL). Studies revealed altered miR-95 expression in several diseases. Long non-coding RNAs (lncRNAs) are a heterogeneous group of non-coding and regulatory RNAs. Aim: The present study was conducted to investigate the association of miR-95 expression with CLL by quantitative real-time PCR. Materials and Methods: Sixty samples, including 30 CLL and 30 healthy controls, were sampled during a period of 4 months. The expression of miR-95 was evaluated by quantitative real-time PCR in peripheral blood mononuclear cells from patients with CLL and in healthy subjects. Additionally, in silico pathway enrichment analysis was performed on validated and predicted targets of miR-95 in several databases, including miRecords and miRTarBase, while the interactions between predicted putative lncRNAs and genes and miRNA expression were examined with miRWalk. Results: The expression of miR-95 was found to be significantly reduced in patients with CLL compared to that in healthy controls (P < 0.005). Conclusion: miR-95 showed potential as a biomarker for the early diagnosis of patients with CLL. LncRNAs play a significant role in regulating cellular evolution, differentiation, and other processes and may be important regulators in tumorigenesis.

scholarly journals Down-regulation of miR-193b-3p and miR-376a-3p in Chronic Lymphocytic Leukemia

2019 ◽  
Author(s):  
Faezeh Namazi ◽  
Nasrin Hadi ◽  
Mansour Moghimi ◽  
Amir Eshaghiyan ◽  
Behnaz Nateghi
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tumor Suppressors ◽  
Mononuclear Cells ◽  
Control Strategies ◽  
Enrichment Analysis ◽  
Lymphocytic Leukemia ◽  
Human Leukemia ◽  
Peripheral Blood Mononuclear ◽  
Diagnostic Biomarkers ◽  
Novel Biomarkers

Background: Chronic lymphocytic leukemia (CLL) is the most common adult human leukemia. Studies revealed that microRNAs (miRNAs) can function as oncogenes or tumor suppressors in CLL and that the expression of miRNAs, such as miR-193b-3p and miR-376a-3p change in several diseases. We aimed to elucidate the changes in miR- 193b-3p and miR-376a-3p expression in CLL and determine their potential as diagnostic biomarkers for this disease. Materials and Methods: We investigated miR-193b-3p and miR-376a-3p expression by quantitative real-time PCR in peripheral blood mononuclear cells of 30 patients with CLL and 30 healthy individuals. Moreover, in silico molecular enrichment analysis was conducted on predicted and validated targets of miR-193b-3p and miR-376a-3p from the miRecords and miRTarBase databases. Results: The expression of miR-193b-3p and miR-376a-3p was significantly different between the two groups (P<0.0001 and P < 0.0001, respectively). Conclusion: Based on these findings, miR-193b-3p and miR-376a-3p could be novel biomarkers for the early diagnosis of CLL and could be used to design new CLL control strategies.

scholarly journals Cytokine influence on killing of fresh chronic lymphocytic leukemia cells by human leukocytes

Blood ◽  
1991 ◽  
Vol 77 (12) ◽  
pp. 2707-2715 ◽  
Author(s):  
D Cemerlic ◽  
B Dadey ◽  
T Han ◽  
L Vaickus
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Mononuclear Cells ◽  
Protein A ◽  
Human Leukocyte ◽  
Lymphocytic Leukemia ◽  
Target Antigen ◽  
Peripheral Blood Mononuclear ◽  
Ifn Gamma ◽  
Hla Dr

Abstract The feasibility of combining the Lym-1 monoclonal antibody (MoAb) with interferon-gamma (IFN-gamma) in the treatment of chronic lymphocytic leukemia (CLL) was evaluated. We used an in vitro tumor lysis model that incorporated fresh CLL cells from 21 different patients as targets for two distinct normal human leukocyte effector subsets, neutrophils, and peripheral blood mononuclear cells (PBMCs). Lym-1 antigen (Lym-1- Ag) expression varied greatly and did not correlate with the expression of other CLL-associated antigens such as CD5, CD19, or HLA-DR. CLL cells were not lysed by neutrophils alone or with IFN-gamma in the absence of Lym-1. Neutrophil Lym-1-dependent cytotoxicity (ADCC) in the absence of IFN-gamma was weak and inconsistent. IFN-gamma exposure induced MoAb-dependent lysis of 80% of 21 CLL targets and resulted in an eightfold augmentation of neutrophil ADCC against the remainder. Cytotoxicity correlated directly and positively with Lym-1-Ag expression. Confirmation of the need for interaction between neutrophil IgG Fc receptors (Fc gamma Rs) and the Fc portion of the Lym-1 MoAb was obtained by demonstrating that purified Staphylococcus aureus Protein A (SpA) inhibited ADCC. IFN-gamma exposure caused no consistent alternations in Lym-1-Ag expression on CLL cells so that target antigen upregulation was unlikely to account for augmentation of neutrophil ADCC. PBMCs alone, exposed to interkeukin-2 (IL-2) or IFN-gamma, or with Lym-1 in the presence or absence of IL-2 or IFN-gamma were unable to lyse CLL targets. PBMCs were able to kill Raji Burkitt lymphoma cells in conjunction with Lym-1, so their ability to interact with Lym- 1-coated targets and their lytic functions appeared intact. These results emphasize the importance of examining fresh tumor cells with different leukocyte effector subsets before designing a clinical trial that combines a therapeutic MoAb with a cytokine.

scholarly journals Evidence for progenitors of chronic lymphocytic leukemia B cells that undergo intraclonal differentiation and diversification

Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1586-1594 ◽  
Author(s):  
M Dono ◽  
S Hashimoto ◽  
F Fais ◽  
V Trejo ◽  
SL Allen ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Dna Sequences ◽  
Mononuclear Cells ◽  
Lymphocytic Leukemia ◽  
Specific Primers ◽  
Region Gene ◽  
Peripheral Blood Mononuclear ◽  
Ancestral Gene

Peripheral blood mononuclear cells from five patients with IgG+ B-type chronic lymphocytic leukemia (B-CLL) were analyzed for the presence of clone-specific Ig H chain variable region gene mRNA transcripts linked to C mu and/or C alpha. This was assessed by (1) comparing the lengths of portions of the VHDJH of the IgG+ CLL clones with those of the mu and alpha isotype-expressing B cells, (2) performing clone-specific endonuclease digestion studies, and (3) determining the DNA sequences of the mu and alpha isotype-expressing cDNA. Thus, when B-cell mRNA from these five patients were reverse transcribed with C gamma-specific primers and then amplified by polymerase chain reaction, dominant cDNA were found with lengths corresponding to those of the IgG+ CLL B cell. In addition, in four cases, cDNA of lengths identical to those of the CLL B cell were detected when mRNA was reverse transcribed and amplified using c mu- and/or C alpha-specific primers, strongly suggesting clonal relatedness. These CLL-related mu- and alpha- expressing cDNA were present in greater amounts that unrelated (non- CLL) mu- and alpha-expressing cDNA from normal B cells that used genes of the same VH family. When the sequences of these CLL-related C mu- and C alpha-expressing cDNA were compared with those of the IgG+ CLL clones, it was clear that they were derived from the same ancestral gene as the IgG-expressing CLL B cell, thus documenting their common origin. Finally, nucleotide point mutations were observed in the mu- and alpha-expressing cDNA of certain patients, indicating divergence with the CLL. These data suggest that IgM+ B cells, which are precursors of the leukemic B cells, exist in increased numbers in the blood of most patients with IgG+ B-CELL and that these cells may differentiate, accumulate V genes mutations, and undergo isotype switching in vivo. In addition, the data are consistent with a sequential-hit model for the evolution of CLL.

Expression of Programmed Death 1 Ligand in Different Compartments of Chronic Lymphocytic Leukemia

2015 ◽  
Vol 134 (4) ◽  
pp. 255-262 ◽  
Author(s):  
Maciej Grzywnowicz ◽  
Agnieszka Karczmarczyk ◽  
Katarzyna Skorka ◽  
Malgorzata Zajac ◽  
Joanna Zaleska ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Lymphocytic Leukemia ◽  
Strongly Correlated ◽  
Peripheral Blood Mononuclear ◽  
Programmed Death ◽  
Distinct Disease ◽  
Programmed Death 1

Background: The programmed death 1 (PD-1) receptor pathway is responsible for the negative regulation of both T and B lymphocytes upon activation of these cells. There is growing evidence that chronic lymphocytic leukemia (CLL) cells exploit the PD-1 ligand (PD-L1) to resist antitumor immune reactions and maintain their survival by shaping their own microenvironment. Methods: We used a quantitative RT-PCR method to analyze PD-L1 gene expression in bone marrow and peripheral blood mononuclear cells, representing the proliferation and accumulation compartments of CLL. Results: PD-L1 expression was found to be significantly higher in 112 CLL patients than in controls. Levels of PD-L1 expression in bone marrow and peripheral blood were comparable and showed a positive correlation. Furthermore, expression of PD-L1 strongly correlated with expression of PD-1 receptor in mononuclear cells from the same compartment, and was not affected by incubation with immunomodulatory drug thalidomide. Conclusion: PD-L1 expression is shared between CLL cells localized in distinct disease compartments, demonstrating that PD-1/PD-L1 a universal target for therapy.

Methylation Profile of B-Chronic Lymphocytic Leukemia Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2951-2951
Author(s):  
Jun Fan ◽  
Asou Norio ◽  
Masao Matsuoka
Keyword(s):  
Dna Methylation ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Lines ◽  
Mammalian Cells ◽  
Mononuclear Cells ◽  
Cpg Island ◽  
Methylation Status ◽  
Lymphocytic Leukemia ◽  
Dna Hypomethylation ◽  
Peripheral Blood Mononuclear

Abstract DNA methylation plays an important role in the development and aging of mammalian cells, and its dysregulation has been frequently observed in cancer cells. The purpose of this study is to investigate the involvement of aberrant DNA methylation in B chronic lymphocytic leukemia (B-CLL) cells. We compared methylation status of B-CLL cells isolated from patients with that of normal CD19+ cells isolated from health donors by methylated CpG island amplification/representative difference analysis method. 5 hypermethylated and 27 hypomethylated DNA regions were identified in B-CLL sample. Among the 27 hypomethylated regions, 5 located on chromosome 9q34, 3 on 10q25-26 and 4 on 19q13. Methylation status was confirmed by sequencing using sodium bisulfite-treated DNA samples. By comparing DNA samples from same patients at different clinical stages, we found that lower methylation density in these regions is linked with disease progression. Expression of 15 genes surrounding hypomethylated regions was studied by RT-PCR. Expression of laminin beta3 gene and melanotransferrin gene was found to be upregulated in all B-CLL cell lines as well as lymphoma cell lines comparing with normal CD19+ peripheral blood mononuclear cells. B-cell CLL/lymphoma 11b gene showed increased expression in only 2 B-CLL cell lines. For other genes, no transcriptional change was found regardless of changed DNA methylation. This study showed the predominance of DNA hypomethylation in B-CLL cells compared with hypermethylation. Hypomethylated regions clustered in a limited number of chromosomes and methylation density appeared to be inversely correlated with disease progress. Figure Figure

The Receptor for Hyaluronic Acid Mediated Motility (RHAMM/CD168) Is a Potential Target for Immunotherapy of Patients with B-Cell Chronic Lymphocytic Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 53-53 ◽  
Author(s):  
Krzysztof Giannopoulos ◽  
Iwona Hus ◽  
Li Li ◽  
Agnieszka Bojarska-Junak ◽  
Jochen Greiner ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Mononuclear Cells ◽  
Tissue Expression ◽  
T Cell Response ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Peripheral Blood Mononuclear ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Definition of appropriate target antigens might open new avenues to antigen targeted immunotherapies for patients with B-cell chronic lymphocytic leukemia (B-CLL). We screened the mRNA expression of tumor associated antigens (TAAs), from the literature (fibromodulin, survivin, OFA-iLRP, BAGE, G250, MAGE1, PRAME, proteinase, Syntaxin, hTERT, WT-1), and TAAs defined earlier by serological analysis of cDNA expression libraries from leukemic cells (PINCH, HSJ2, MAZ, MPP11, RHAMM/CD168, NY-Ren60). Peripheral blood mononuclear cells from 43 B-CLL patients and 20 healthy volunteers (HVs) were examined by conventional and quantitative RT-PCR. mRNA of RHAMM/CD168, fibromodulin, syntaxin and NY-Ren60 was expressed in 55–90%, mRNA of HSJ2, MAZ and OFA-iLRP in 90–100% of the patients. No expression of WT-1, h-TERT, BAGE, G250, MAGE1 and survivin was observed. Low (2–20%) expression frequencies of MPP11, PINCH, PRAME and proteinase were detected. RHAMM/CD168, fibromodulin, PRAME and MPP11 showed expression in B-CLL patients, but not in HVs. Because of the exquisite tissue expression of RHAMM/CD168 and its high expression frequency in B-CLL patients even in early stages of disease, mixed lymphocyte peptide culture (MLPC), enzyme-linked immunosorbent spot (ELISPOT) and flow cytometry were performed for antigen specific T cells. In MLPC, RHAMM specific responses by CD8+HLA-A2/R3tetramer+CCR7-CD45RAhigh effector T cells were detected. Moreover, we observed an enhanced RHAMM/CD168 specific CD8+ T cell response after vaccination in one from four HLA-A2 positive B-CLL patients vaccinated with tumor cell lysate pulsed dendritic cells. Therefore, RHAMM/CD168 is an interesting candidate antigen for future immunotherapies in both ZAP-70 (+) and ZAP-70 (−) B-CLL patients.

scholarly journals Impact of Berberine on the Expression of Apollon Gene in Chronic Lymphocytic Leukemia

2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Niloofar Ghanizade ◽  
Maral Hemati ◽  
Habib Jaafarinejad ◽  
Mehrnoosh Pashaei ◽  
Parviz Kokhaei
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Blood Mononuclear Cells ◽  
The Impact

Background: The incidence of B-chronic lymphocytic leukemia (B-CLL) resulting from the clonal accumulation of apoptosis-resistant malignant B lymphocytes is growing in the adult population of Iran. Inhibitors of apoptosis proteins (IAPs) are considered as factors that can delay the onset of CLL cell apoptosis. Berberine is an isoquinoline alkaloid isolated from Cotridis rhizoma that exhibits anti-tumor activities through various mechanisms. Objectives: In this study, we investigated the impact of berberine on the level of Apollon expression in peripheral blood mononuclear cells (PBMCs) of 12 cases newly diagnosed with CLL and 6 healthy donors. Methods: At first, the level of Apollon expression was assessed in PBMCs of CLL patients compared to the healthy donors. Peripheral blood mononuclear cells were cultured in RPMI-1640 medium with 5% fetal bovine serum (FBS) and 1% penicillin/streptomycin for 48 hours, and the effect of berberine (25 µM) on the level of Apollon expression in CLL patients was assessed and compared to that of healthy donors. Results: We found that the expression level of Apollon was not significantly different between CLL patients and healthy donors (P = 0.640). Moreover, berberine induced no significant differences in Apollon expression as compared to the untreated (control) group (P = 0.545 and P = 0.267 in CLL patients and healthy donors, respectively). Conclusions: Overall, our results suggest that berberine has no direct effect on the expression of Apollon gene in CLL patients, and pro-apoptotic impacts of berberine may be exerted through other mechanisms.

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