Altered expression pattern of SLAM family receptors on pathological B cells of patients with chronic lymphocytic leukemia

2016 ◽  
Vol 58 (7) ◽  
pp. 1726-1729 ◽  
Author(s):  
Matus Coma ◽  
Elena Tothova ◽  
Tomas Guman ◽  
Martina Hajikova ◽  
Maria Giertlova ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Expression Pattern ◽  
Lymphocytic Leukemia ◽  
Altered Expression ◽  
Altered Expression Pattern ◽  
Slam Family

Changes in the expression of telomere maintenance genes suggest global telomere dysfunction in B-chronic lymphocytic leukemia

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 2388-2391 ◽  
Author(s):  
Delphine Poncet ◽  
Aurélie Belleville ◽  
Claire t'Kint de Roodenbeke ◽  
Aude Roborel de Climens ◽  
Elsa Ben Simon ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Telomere Length ◽  
Expression Pattern ◽  
Prognostic Marker ◽  
Lymphocytic Leukemia ◽  
Telomere Maintenance ◽  
Telomere Dysfunction ◽  
Healthy Donors ◽  
Differential Expression Pattern

In this study, we explored the telomeric changes that occur in B-chronic lymphocytic leukemia (B-CLL), in which telomere length has recently been demonstrated to be a powerful prognostic marker. We carried out a transcriptomic analysis of telomerase components (hTERT and DYSKERIN), shelterin proteins (TRF1, TRF2, hRAP1, TIN2, POT1, and TPP1), and a set of multifunctional proteins involved in telomere maintenance (hEST1A, MRE11, RAD50, Ku80, and RPA1) in peripheral B cells from 42 B-CLL patients and 20 healthy donors. We found that, in B-CLL cells, the expressions of hTERT, DYSKERIN, TRF1, hRAP1, POT1, hEST1A, MRE11, RAD50, and KU80 were more than 2-fold reduced (P < .001), contrasting with the higher expression of TPP1 and RPA1 (P < .001). This differential expression pattern suggests that both telomerase down-regulation and changes in telomeric proteins composition are involved in the pathogenesis of B-CLL.

THE ROLE OF THE GENETIC ABNORMALITIES, EPIGENETIC AND microRNA IN THE PROGNOSIS OF CHRONIC LYMPHOCYTIC LEUKEMIA

2018 ◽  
Vol 40 (4) ◽  
pp. 261-267 ◽  
Author(s):  
K Tari ◽  
Z Shamsi ◽  
H Reza Ghafari ◽  
A Atashi ◽  
M Shahjahani ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Kinase Inhibitors ◽  
Bone Marrow Involvement ◽  
P53 Mutation ◽  
Lymphocytic Leukemia ◽  
Gene Promoters ◽  
Epigenetic Changes ◽  
Genetic Changes ◽  
Trisomy 12

Chronic lymphocytic leukemia (CLL) is increased proliferation of B-cells with peripheral blood and bone marrow involvement, which is usually observed in older people. Genetic mutations, epigenetic changes and miRs play a role in CLL pathogenesis. Del 11q, del l17q, del 6q, trisomy 12, p53 and IgVH mutations are the most important genetic changes in CLL. Deletion of miR-15a and miR-16a can increase bcl2 gene expression, miR-29 and miR-181 deletions decrease the expression of TCL1, and miR-146a deletion prevents tumor metastasis. Epigenetic changes such as hypo- and hypermethylation, ubiquitination, hypo- and hyperacetylation of gene promoters involved in CLL pathogenesis can also play a role in CLL. Expression of CD38 and ZAP70, presence or absence of mutation in IgVH and P53 mutation are among the factors involved in CLL prognosis. Use of monoclonal antibodies against surface markers of B-cells like anti-CD20 as well as tyrosine kinase inhibitors are the most important therapeutic approaches for CLL.

scholarly journals Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ana Colado ◽  
Esteban Enrique Elías ◽  
Valeria Judith Sarapura Martínez ◽  
Gregorio Cordini ◽  
Pablo Morande ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphocytic Leukemia ◽  
Immunomodulatory Effects ◽  
Immunoglobulin Preparations

AbstractHypogammaglobulinemia is the most frequently observed immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of all isotypes (IgG, IgM and IgA), standard immunoglobulin (Ig) preparations for replacement therapy administrated to these patients contain more than 95% of IgG. Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM and IgA (IVIgGMA), with the potential benefit to restore the Ig levels of all isotypes. Because IVIg preparations at high doses have well-documented anti-inflammatory and immunomodulatory effects, we aimed to evaluate the capacity of Pentaglobin and a standard IVIg preparation to affect leukemic and T cells from CLL patients. In contrast to standard IVIg, we found that IVIgGMA did not modify T cell activation and had a lower inhibitory effect on T cell proliferation. Regarding the activation of leukemic B cells through BCR, it was similarly reduced by both IVIgGMA and IVIgG. None of these IVIg preparations modified spontaneous apoptosis of T or leukemic B cells. However, the addition of IVIgGMA on in vitro cultures decreased the apoptosis of T cells induced by the BCL-2 inhibitor, venetoclax. Importantly, IVIgGMA did not impair venetoclax-induced apoptosis of leukemic B cells. Overall, our results add new data on the effects of different preparations of IVIg in CLL, and show that the IgM/IgA enriched preparation not only affects relevant mechanisms involved in CLL pathogenesis but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation.

scholarly journals Analysis with antiidiotype antibody of a patient with chronic lymphocytic leukemia and a large cell lymphoma (Richter's syndrome)

Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 45-50 ◽  
Author(s):  
LF Bertoli ◽  
H Kubagawa ◽  
GV Borzillo ◽  
M Mayumi ◽  
JT Prchal ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Plasma Cells ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Lymphocytic Leukemia ◽  
Immunoglobulin Gene ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma ◽  
Richter’S Syndrome

Abstract A murine monoclonal antibody made against an idiotypic determinant (Id) of surface IgM/IgD lambda molecules on chronic lymphocytic leukemia (CLL) cells of a 71-year-old woman was used for clonal analysis by two- color immunofluorescence. The anti-Id antibody identified IgM+/IgD+/lambda+ B cells as the predominant cell type of her CLL clone. In addition, substantial proportions of the IgG and IgA B cells and most of the IgM plasma cells in her bone marrow and blood were Id+. Six years after diagnosis, the patient died of respiratory failure due to infiltration of lungs by malignant cells. Autopsy revealed a dramatic change in the tumor cell morphology. The lungs, hilar nodes, and liver were infiltrated by a diffuse large cell lymphoma admixed with the leukemic cells. By immunohistologic staining these anaplastic lymphoma cells were IgM+/IgD-/lambda+ B cells expressing the same Id noted earlier on the CLL cells. The immunoglobulin gene rearrangement pattern on Southern blot analysis was also the same in leukemic blood cells and in the tissues involved by the lymphoma. Thus, the combination of antiidiotype and immunoglobulin gene analyses in this patient with Richter's syndrome revealed that a CLL clone, seemingly “frozen” in differentiation, was actually undergoing isotype switching, differentiation into plasma cells, and evolution into a rapidly growing and fetal lymphoma.

Altered Expression Pattern of Acid-Sensing Ion Channel Isoforms in Piriform Cortex After Seizures

2015 ◽  
Vol 53 (3) ◽  
pp. 1782-1793 ◽  
Author(s):  
Hao Wu ◽  
Chao Wang ◽  
Bei Liu ◽  
Huanfa Li ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Ion Channel ◽  
Expression Pattern ◽  
Piriform Cortex ◽  
Altered Expression ◽  
Altered Expression Pattern

scholarly journals Targeted inhibition of eIF4A suppresses B-cell receptor-induced translation and expression of MYC and MCL1 in chronic lymphocytic leukemia cells

2021 ◽  
Author(s):  
Sarah Wilmore ◽  
Karly-Rai Rogers-Broadway ◽  
Joe Taylor ◽  
Elizabeth Lemm ◽  
Rachel Fell ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Mrna Translation ◽  
Cell Receptor ◽  
Memory B Cells ◽  
B Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Mrna Levels ◽  
Mrna Stabilization

AbstractSignaling via the B-cell receptor (BCR) is a key driver and therapeutic target in chronic lymphocytic leukemia (CLL). BCR stimulation of CLL cells induces expression of eIF4A, an initiation factor important for translation of multiple oncoproteins, and reduces expression of PDCD4, a natural inhibitor of eIF4A, suggesting that eIF4A may be a critical nexus controlling protein expression downstream of the BCR in these cells. We, therefore, investigated the effect of eIF4A inhibitors (eIF4Ai) on BCR-induced responses. We demonstrated that eIF4Ai (silvestrol and rocaglamide A) reduced anti-IgM-induced global mRNA translation in CLL cells and also inhibited accumulation of MYC and MCL1, key drivers of proliferation and survival, respectively, without effects on upstream signaling responses (ERK1/2 and AKT phosphorylation). Analysis of normal naïve and non-switched memory B cells, likely counterparts of the two main subsets of CLL, demonstrated that basal RNA translation was higher in memory B cells, but was similarly increased and susceptible to eIF4Ai-mediated inhibition in both. We probed the fate of MYC mRNA in eIF4Ai-treated CLL cells and found that eIF4Ai caused a profound accumulation of MYC mRNA in anti-IgM treated cells. This was mediated by MYC mRNA stabilization and was not observed for MCL1 mRNA. Following drug wash-out, MYC mRNA levels declined but without substantial MYC protein accumulation, indicating that stabilized MYC mRNA remained blocked from translation. In conclusion, BCR-induced regulation of eIF4A may be a critical signal-dependent nexus for therapeutic attack in CLL and other B-cell malignancies, especially those dependent on MYC and/or MCL1.

scholarly journals Altered expression pattern of testican-1 mRNA after brain injury

2011 ◽  
Vol 32 (6) ◽  
pp. 373-378 ◽  
Author(s):  
Ken Iseki ◽  
Seita Hagino ◽  
Yuxiang Zhang ◽  
Tetsuji Mori ◽  
Nobuko Sato ◽  
...  
Keyword(s):  
Brain Injury ◽  
Expression Pattern ◽  
Altered Expression ◽  
Altered Expression Pattern

scholarly journals Aberrant splicing of the E-cadherin transcript is a novel mechanism of gene silencing in chronic lymphocytic leukemia cells

Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4179-4185 ◽  
Author(s):  
Sanjai Sharma ◽  
Alan Lichtenstein
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Premature Termination ◽  
Ectopic Expression ◽  
Premature Termination Codon ◽  
Lymphocytic Leukemia ◽  
Termination Codon ◽  
Nonsense Mediated Decay ◽  
Aberrant Transcript ◽  
E Cadherin

Abstract Premature termination codon (PTC) mutations are due to insertion or deletion of nucleotides causing a frameshift and premature termination codon in RNA. These transcripts are degraded by the nonsense-mediated decay pathway and have a very short half-life. We used a microarray technique to screen for genes that up-regulate their RNA signal upon nonsense-mediated decay pathway blockade in chronic lymphocytic leukemia (CLL) specimens and identified an E-cadherin transcript with PTC. Sequencing revealed an aberrant E-cadherin transcript lacking exon 11, resulting in a frameshift and PTC. The aberrant E-cadherin transcript was also identified in normal B cells, but occurred at a much lower level compared with CLL cells. In CLL specimens, E-cadherin expression was depressed more than 50% in 62% cases (relative to normal B cells). By real-time polymerase chain reaction analysis, the relative amounts of wild-type transcript inversely correlated with amounts of aberrant transcript (P = .018). Ectopic expression of E-cadherin in CLL specimens containing high amounts of aberrant transcript resulted in down-regulation of the wnt–β-catenin pathway reporter, a pathway known to be up-regulated in CLL. Our data point to a novel mechanism of E-cadherin gene inactivation, with CLL cells displaying a higher proportion of aberrant nonfunctional transcripts and resulting up-regulation of the wnt–β-catenin pathway.

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