scholarly journals Analysis of CD38 and ZAP70 mRNA expression among cytogenetic subgroups of Iranian chronic-lymphocytic-leukemia patients

2011 ◽  
Vol 10 (4) ◽  
pp. 2415-2423 ◽  
Author(s):  
H. Teimori ◽  
M.T. Akbari ◽  
M. Hamid ◽  
M. Forouzandeh ◽  
E. Bibordi
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Mrna Expression ◽  
Lymphocytic Leukemia

High CD49d protein and mRNA expression predicts poor outcome in chronic lymphocytic leukemia

2009 ◽  
Vol 131 (3) ◽  
pp. 472-480 ◽  
Author(s):  
Holger Nückel ◽  
Magdalena Switala ◽  
Crista H. Collins ◽  
Ludger Sellmann ◽  
Hans Grosse-Wilde ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Mrna Expression ◽  
Lymphocytic Leukemia ◽  
Poor Outcome

scholarly journals Low MCL-1 mRNA expression correlates with prolonged survival in B-cell chronic lymphocytic leukemia

Leukemia ◽  
2007 ◽  
Vol 22 (6) ◽  
pp. 1291-1293 ◽  
Author(s):  
L Véronèse ◽  
O Tournilhac ◽  
P Verrelle ◽  
F Davi ◽  
G Dighiero ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Mrna Expression ◽  
Lymphocytic Leukemia ◽  
Prolonged Survival ◽  
Cell Chronic Lymphocytic Leukemia

scholarly journals A Study of Ribonucleotide Reductase mRNA Expression and Its Prognostic Role in Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4678-4678
Author(s):  
Sevastianos Chatzidavid ◽  
Christina-Nefeli Kontandreopoulou ◽  
Panagiotis T Diamantopoulos ◽  
Nefeli Giannakopoulou ◽  
Panagiota Katsiampoura ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Mrna Expression ◽  
Board Of Directors ◽  
Ribonucleotide Reductase ◽  
Research Funding ◽  
Lymphocytic Leukemia ◽  
Line Treatment ◽  
Prognostic Role ◽  
Advisory Committees ◽  
Trisomy 12

Abstract Background Ribonucleotide Reductase (RNR) is responsible for converting ribonucleotides to deoxyribonucleotides required for DNA replication and repair. RNR consists of two subunits, termed subunit 1 (RRM1) and 2 (RRM2). Imbalance in the regulation of RNR activity and control of dNTPs' pool leads to genomic instability and increases mutation rate. RNR expression has been associated with prognosis in pancreatic, non-small-cell lung, breast, and biliary tract cancer. However, RNR expression in chronic lymphocytic leukemia (CLL) and its possible prognostic role have not been investigated yet. Aim In this study we evaluate the possible prognostic role of RNR expression in CLL. Method The study comprised patients with immunophenotypically confirmed disease at the time of sample collection. Peripheral whole blood samples were collected from 84, 27, 15, and 9 patients before treatment, after one, two, and three lines of treatment respectively. RNA extraction and reverse transcription were carried out using standard protocols. A Taqman based real-time PCR was performed on a CFX96 RT-PCR system (Bio-Rad Laboratories, Hercules, CA, USA). For both the housekeeping and target genes, a Taqman primer/probe mix was used according to the manufacturer's instructions (Applied Biosystems, Foster City, CA, USA). RRM1 and RRM2 mRNA levels were expressed as an RRM1-2/GAPDH ratio. Western blot analysis was performed to quantify the RRM1 protein levels in a random sample of 41 patients. Antibodies used were: RRM1 #3388, β-actin #4967 and anti-rabbit IgG HRP-conjugated #7074 (Cell Signaling Technology, Danvers, MA, USA). Detection was done using the ECL western blotting reagents. Statistical analysis was conducted to study the possible correlations between the variables. All reported p values are two-tailed. Statistical significance was set at p<0.05 and analyses were conducted using SPSS statistical software (version 22.0). Results From 135 CLL patients included in the study 56.3% were female and the median age at diagnosis was 64 years. Peripheral blood was collected in 84 treatment-naïve patients (62.2%). Median follow up was 6.66 years (3.47 ─ 11.13) and median time from diagnosis until 1st line treatment was 23.1 months (IQR: 5.8 - 56.5 months). Out of 135 patients, 69 (51,1%) received 1 st line treatment and 35 patients (25,9%) 2 nd line treatment with median time between the two treatment lines being 26.5 months (IQR: 7.8 - 40.8 months). Furthermore, 48.5%, 33.8%, 12.3%, 3.1% and 2.3% of the patients had Rai score 0, I, II, III, IV respectively. The median mRNA expression of RRM1 was 0.04 (IQR: 0 - 0.09) and of RRM2 was 0.01 (IQR: 0 - 0.1). RRM1 mRNA expression was significantly higher in patients without anemia (p=.025) and without lymphadenopathy (p=.002). Higher values of ESR (r=-.30; p=.028), LDH (r=-.20; p=.026) and Rai score (r=-.18; p=.037) were associated with lower expression of RRM1 mRNA. In addition, TP53 gene deletion detected by FISH was associated with higher RRM1 mRNA expression (p=.036). Significantly higher RRM2 mRNA expression was reported in patients without lymphadenopathy (p=.021) and Rai score 0 (p=.003). Moreover, higher was the expression of RRM2 mRNA in cases with Trisomy 12 (p=.050). In samples collected before treatment, higher values of RRM1 mRNA expression were statistically significantly associated with lower RAI score (r=-.30; p=.005) and longer time periods between the first two lines of treatment (r=.95; p=.050). Western blot analysis confirmed detection of RRM1 protein but statistical correlation was not carried out due to lack of material from the whole group of patients. Conclusion For the first time, mRNA expression of RRM1 and RRM2 is studied in patients with CLL. These results show RNR involvement in the pathophysiology of CLL. RRM1 and RRM2 mRNA higher expression found in 17p deletion and trisomy 12 cases respectively may be consistent with the existence of a methylation-depended mechanism proposed by other studies. Therefore, these results demonstrate RNR's potential role as a prognostic factor, and make it a probable therapeutic target. A study including a larger number of cases could further confirm our results. Figure 1 Figure 1. Disclosures Kyrtsonis: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene/Genesis Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria; Sanofi: Membership on an entity's Board of Directors or advisory committees. Panagiotidis: Abbvie: Research Funding; Pfizer: Research Funding; Janssen: Research Funding; Sanofi: Research Funding; Novartis: Research Funding; Takeda: Research Funding; Sandoz: Research Funding; Bristol-Myers Squibb: Research Funding; Roche: Research Funding; Astellas: Research Funding. Viniou: Sandoz: Research Funding; Takeda: Research Funding; Novartis: Honoraria, Research Funding; Sanofi: Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Research Funding; Abbvie: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Roche: Research Funding; Astellas: Research Funding; Celgene: Research Funding.

scholarly journals Cytokine gene expression in B-cell chronic lymphocytic leukemia: evidence of constitutive interleukin-8 (IL-8) mRNA expression and secretion of biologically active IL-8 protein

Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 220-228 ◽  
Author(s):  
PF di Celle ◽  
A Carbone ◽  
D Marchis ◽  
D Zhou ◽  
S Sozzani ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Mrna Expression ◽  
Interleukin 1 ◽  
Constitutive Expression ◽  
Lymphocytic Leukemia ◽  
Biologically Active ◽  
Leukemic Cells ◽  
Cytokine Gene Expression ◽  
Cell Chronic Lymphocytic Leukemia

Abstract To extent our knowledge on the cytokines possibly involved in the pathophysiology of B-cell chronic lymphocytic leukemia (B-CLL), the mRNA expression of a panel of 10 cytokines was investigated on purified B-CLL cells using a reverse-transcriptase polymerase chain reaction method. Whereas negative RT-PCR signals were recorded for interleukin-1 alpha (IL-1 alpha), IL-2, IL-3, IL-4, IL-5, IL-7, tumor necrosis factor beta (TNF beta), and granulocyte-macrophage colony-stimulating factor, we detected the expression of IL-1 beta, IL-6 and TNF alpha. Furthermore, the constitutive expression of IL-8 mRNA was observed in all 17 B-CLL samples analyzed. mRNA expression was associated with the capacity of the leukemic cells to release IL-8 both constitutively (4.6 +/- 8.1 SD ng/mL) and, to a further extent, after stimulation (14.5 +/- 19.4 ng/mL). The circulating levels of IL-8 were also evaluated in 12 untreated B-CLL sera samples and the overall mean level was significantly higher (P <.01) than in normal sera. In addition, supernatants of purified B-CLL cells cultured in the presence of 12-O- tetradecanoylphorbol-13-acetate showed chemotactic activity towards neutrophils; this activity was neutralized in the presence of an anti- IL-8 antiserum. The mRNA for IL-8 was absent in five B-cell preparations from hairy cell leukemia cases and in four B-cell lines. Normal tonsil CD5+ B cells showed a low expression of IL-8 mRNA only in two of the nine preparations tested and the overall quantity of IL-8 released by these cells after 3 days' incubation was significantly lower compared with that released by B-CLL cells (0.4 +/- 0.3 and 1.6 +/- 0.9 ng/mL under basal and stimulated conditions, respectively). These findings point to an involvement of a member of the proinflammatory chemokine supergene family in human CD5+ B lymphocytes. The different IL-8 behavior observed between B-CLL cells and their normal counterpart is likely to reflect an activation state of the leukemic population.

scholarly journals Lipoprotein Lipase mRNA Expression in Whole Blood Is a Prognostic Marker in B Cell Chronic Lymphocytic Leukemia

2007 ◽  
Vol 53 (2) ◽  
pp. 204-212 ◽  
Author(s):  
Femke Van Bockstaele ◽  
Valerie Pede ◽  
Ann Janssens ◽  
Filip Callewaert ◽  
Fritz Offner ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Mrna Expression ◽  
Lipoprotein Lipase ◽  
Prognostic Marker ◽  
Whole Blood ◽  
Predictive Value ◽  
Variable Region ◽  
Individual Variability ◽  
Lymphocytic Leukemia ◽  
Mutation Status

Abstract Background: Chronic lymphocytic leukemia (CLL) is characterized by high individual variability in clinical course and the need for therapy. Differentiation of prognostic subgroups is based primarily on the mutation status of the genes for the variable region of the immunoglobulin heavy chain (IGHV). The time- and labor-intensive nature of this analysis necessitates the use of easily applicable surrogate markers. Methods: We developed a quantitative PCR (qPCR) method for determining lipoprotein lipase (LPL) mRNA expression and analyzed samples of lysed whole blood and CD19-selected cells from 50 CLL patients. Associations of LPL and ZAP70 [ζ-chain (TCR) associated protein kinase 70 kDa] expression with IGHV mutation status, overall survival (OS), and treatment-free survival (TFS) were investigated. Results: Lysed samples of whole blood and CD19-selected cells were similar with respect to LPL expression (R = 0.88; P &lt;0.0001). LPL expression was significantly associated with IGHV mutation status [χ2(1) = 15.3; P &lt;0.0001] and showed an 89.3% specificity, a 68.2% sensitivity, an 83.3% positive predictive value, and a 78.1% negative predictive value for IGHV mutation status. LPL expression was significantly associated with both OS and TFS in log-rank tests (both P values = 0.002). LPL-positive patients had a significantly shorter median TFS time (23 months) than LPL-negative patients (88 months) (P = 0.002). Conclusions: LPL mRNA expression is a valuable prognostic marker in CLL. The method does not require cell purification, and its applicability with archived samples facilitates its use in the clinical routine and other studies.

Strong correlation between VEGF and MCL-1 mRNA expression levels in B-cell chronic lymphocytic leukemia

2009 ◽  
Vol 33 (12) ◽  
pp. 1623-1626 ◽  
Author(s):  
Lauren Véronèse ◽  
Olivier Tournilhac ◽  
Pierre Verrelle ◽  
Frédéric Davi ◽  
Guillaume Dighiero ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Mrna Expression ◽  
Strong Correlation ◽  
Lymphocytic Leukemia ◽  
Expression Levels ◽  
Mrna Expression Levels ◽  
Cell Chronic Lymphocytic Leukemia

scholarly journals Cytokine gene expression in B-cell chronic lymphocytic leukemia: evidence of constitutive interleukin-8 (IL-8) mRNA expression and secretion of biologically active IL-8 protein

Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 220-228 ◽  
Author(s):  
PF di Celle ◽  
A Carbone ◽  
D Marchis ◽  
D Zhou ◽  
S Sozzani ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Mrna Expression ◽  
Interleukin 1 ◽  
Constitutive Expression ◽  
Lymphocytic Leukemia ◽  
Biologically Active ◽  
Leukemic Cells ◽  
Cytokine Gene Expression ◽  
Cell Chronic Lymphocytic Leukemia

To extent our knowledge on the cytokines possibly involved in the pathophysiology of B-cell chronic lymphocytic leukemia (B-CLL), the mRNA expression of a panel of 10 cytokines was investigated on purified B-CLL cells using a reverse-transcriptase polymerase chain reaction method. Whereas negative RT-PCR signals were recorded for interleukin-1 alpha (IL-1 alpha), IL-2, IL-3, IL-4, IL-5, IL-7, tumor necrosis factor beta (TNF beta), and granulocyte-macrophage colony-stimulating factor, we detected the expression of IL-1 beta, IL-6 and TNF alpha. Furthermore, the constitutive expression of IL-8 mRNA was observed in all 17 B-CLL samples analyzed. mRNA expression was associated with the capacity of the leukemic cells to release IL-8 both constitutively (4.6 +/- 8.1 SD ng/mL) and, to a further extent, after stimulation (14.5 +/- 19.4 ng/mL). The circulating levels of IL-8 were also evaluated in 12 untreated B-CLL sera samples and the overall mean level was significantly higher (P <.01) than in normal sera. In addition, supernatants of purified B-CLL cells cultured in the presence of 12-O- tetradecanoylphorbol-13-acetate showed chemotactic activity towards neutrophils; this activity was neutralized in the presence of an anti- IL-8 antiserum. The mRNA for IL-8 was absent in five B-cell preparations from hairy cell leukemia cases and in four B-cell lines. Normal tonsil CD5+ B cells showed a low expression of IL-8 mRNA only in two of the nine preparations tested and the overall quantity of IL-8 released by these cells after 3 days' incubation was significantly lower compared with that released by B-CLL cells (0.4 +/- 0.3 and 1.6 +/- 0.9 ng/mL under basal and stimulated conditions, respectively). These findings point to an involvement of a member of the proinflammatory chemokine supergene family in human CD5+ B lymphocytes. The different IL-8 behavior observed between B-CLL cells and their normal counterpart is likely to reflect an activation state of the leukemic population.

FCRL2 mRNA expression is inversely associated with clinical progression in chronic lymphocytic leukemia

2009 ◽  
Vol 83 (6) ◽  
pp. 541-549 ◽  
Author(s):  
Holger Nückel ◽  
Crista H. Collins ◽  
Ulrich H. Frey ◽  
Ludger Sellmann ◽  
Jan Dürig ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Mrna Expression ◽  
Lymphocytic Leukemia ◽  
Clinical Progression
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