Serum Tumor Markers in Non-Hodgkin's Lymphomas and Chronic Lymphocytic Leukemia

1993 ◽  
Vol 8 (1) ◽  
pp. 14-20 ◽  
Author(s):  
A.N. Pavlidis ◽  
J. Kalef-Ezra ◽  
L.C. Bourantas ◽  
A. Lambrou ◽  
A. Mavridis
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tumor Markers ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Interleukin 2 ◽  
Serum Levels ◽  
Lymphocytic Leukemia ◽  
Mean Values ◽  
Hodgkin's Lymphomas ◽  
Normal Controls

The levels of soluble interleukin-2 receptors (sIL-2R), beta-2 microglobulin (β-2M), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured in the serum of 50 previously untreated patients with non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL) as well as in 25 age and sex-matched normal controls. Compared to normal controls, mean serum levels of sIL-2R and β-2M were significantly increased in both NHL and CLL (p < 0.001) while the increase in ESR and CRP was less marked (p < 0.01 and p < 0.05, respectively). Comparison of these tumor markers with histologic grading showed statistically significant differences only for CRP between low, intermediate and high-grade lymphomas (p < 0.001 and p < 0.05). More advanced stages exhibited higher mean values of all serum markers than early stages (p < 0.001 for sIL-2R, β-2M and ESR and p < 0.05 for CRP). An association with the presence of b-symptoms was observed only for sIL-2R (p < 0.05). In addition, sIL-2R as well as β-2M were able to predict time to progression in patients with diffuse large-cell lymphomas. We conclude that of the four tumor markers tested sIL-2R and β-2M more frequently showed increased serum levels and were associated with clinical stage and/or presence of b-symptoms. Both sIL-2R and β-2M were also found to have prognostic significance for survival.

BAFF and APRIL in Chronic Lymphocytic Leukemia: Clinico-Biological Correlates and Prognostic Significance.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1235-1235 ◽  
Author(s):  
Gerardo Ferrer ◽  
Kate E Hodgson ◽  
Pau Abrisqueta ◽  
Aina Pons ◽  
Sonia Jansa ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lymphocyte Count ◽  
Blood Lymphocyte ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Serum Levels ◽  
Lymphocytic Leukemia ◽  
Advanced Clinical Stage

Abstract Abstract 1235 Poster Board I-257 BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand) are TNF family proteins that upregulate anti-apoptotic genes through the NF-kB pathway. Studies in vitro suggest that BAFF and APRIL protect neoplastic B cells from apoptosis in chronic lymphoproliferative disorders (CLPD) including chronic lymphocytic leukemia (CLL). Serum BAFF levels have been previously shown to be lower in CLL than in other CLPD or normal subjects. To contribute to a better understanding of their role in CLL, we analyzed BAFF and APRIL at mRNA and protein serum levels and their receptors [transmembrane activator and CAML interactor (TACI), B-cell maturation antigen (BCMA) and BAFF receptor (BAFF-R)] by flow cytometry, in 82 patients with CLL, 36 with other CLPD and 35 age- and sex-matched controls. mRNA BAFF and APRIL levels were calculated as a the percentage of expression referred to an internal control and the receptor expression as the ratio between the mean fluorescence intensity (MFI) of the receptor antibody and the MFI of the isotype control. Patients with CLL showed significantly lower median BAFF and APRIL levels (0.63 μg/ml and 3.18 μg/ml) than those with other CLPD (1.27 μg/ml and 5.51 μg/ml) (p<0.05). Moreover, BAFF but not APRIL was lower in CLL than in healthy subjects (0.63 μg/ml vs. 0.77 μg/ml; p<0.0001). Serum BAFF levels and blood lymphocyte counts were inversely correlated. Likewise, in follicular lymphoma patients who had circulating neoplastic B cells, median BAFF levels was 0.84 μg/ml vs. 1.46 μg/ml in those without detectable neoplastic cells in blood (p<0.05). We also examined the expression of BAFF and APRIL in purified CD19+ cells from 19 CLL patients and 10 healthy controls. All CLL and normal B cells expressed BAFF and APRIL although heterogeneously. Nevertheless, BAFF and APRIL were lower in CLL than in normal B cells (median: 6.24% and 12.73% in CLL vs. 11.54% and 42.26% in controls). In CLL, mRNA BAFF expression inversely correlated with BAFF serum levels. As far as BAFF and APRIL receptors are concerned, BAFF-R was the one most highly expressed in CLL and normal B cells (MFI ratios of 167.3 and 157.2, respectively). TACI and BCMA were also expressed in all CLL cells and normal B cells (MFI ratios TACI: 1.70 and 2.41; BCMA: 9.51 and 4.72, respectively), but at a significantly lower level than BAFF-R (p<0.001). Furthermore, whereas BCMA MFI ratio was significantly higher in CLL than in normal B cells (p<0.05), no differences were observed in the expression of TACI and BAFF-R. TACI expression was heterogenous in CLL cells. BAFF-R inversely correlated with BAFF and APRIL serum levels. From a clinical standpoint, there is some indication that BAFF and APRIL serum levels as well as their expression in CLL cells may correlate with clinical and biological characteristics of the disease. No significant relationship was observed between BAFF and APRIL and IGVH mutational status, ZAP-70, CD38 or cytogenetics. However, an inverse correlation was observed between BAFF serum levels and blood lymphocyte counts as well as advanced clinical stage (p<0.05). In contrast, APRIL serum levels were only correlated with CD38 expression, the higher the expression of CD38 the higher the APRIL. Although blood lymphocyte counts and BAFF serum levels are correlated, a multivariate analysis showed that these two variables along with poor risk cytogenetics were independent predictors of progression (poor risk cytogenetics RR=11.699, p<0.05; high blood lymphocyte count RR=9.780, p<0.05 and low serum BAFF RR= 6.098, p<0.05). In summary this study confirms that BAFF and APRIL serum levels are lower in CLL than in other CLPD. In patients with CLL, BAFF serum and mRNA levels correlate with blood lymphocyte count and advanced clinical stage but not with other well known prognostic factors. Finally, although BAFF correlates with blood lymphocyte counts, our results suggest that BAFF serum levels have independent prognostic significance. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic significance of immunoglobulin phenotype in B cell chronic lymphocytic leukemia

Blood ◽  
1985 ◽  
Vol 65 (2) ◽  
pp. 340-344 ◽  
Author(s):  
L Baldini ◽  
R Mozzana ◽  
A Cortelezzi ◽  
A Neri ◽  
F Radaelli ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Clinical Prognosis ◽  
Delta Type ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Seventy-six consecutive untreated patients with B cell chronic lymphocytic leukemia (B-CLL) and classified according to Binet's staging system were studied at the clinical presentation. Several immunologic parameters (number of total and T circulating lymphocytes and their surface membrane immunoglobulin [Smlg] phenotypes and levels of serum Ig) were evaluated with the aim of identifying a biologic marker of prognostic relevance. In this series of persons, Binet staging confirmed its usefulness as a prognostic index (P less than .001). With regard to Smlg, they were mu-type in 41 cases (53.9%), mu- type plus delta-type in 29 cases (38.2%), alpha-type in one case, and not detectable in five cases. No correlations were found between clinical stage and immunoglobulin phenotype, although all but one patient in stage C showed mu-type Smlg alone. On analyzing the survival curves of our patients according to different Smlg phenotypes, we found that patients with only mu-type Smlg had a poorer prognosis (P less than .05) than those with mu-type plus delta-type; this difference was even more significant (P less than .01) in patients in stage A, whereas there were no statistical differences in those in stages B and C. Because the appearance of surface heavy chain of delta-type could be an expression of cell maturation, these results suggest that in B-CLL the presence of phenotypically more mature leukemic cells may correlate with better clinical prognosis, particularly in the early phase of the disease.

Abdominal Computed Tomography Predicts Progression in Patients With Rai Stage 0 Chronic Lymphocytic Leukemia

2007 ◽  
Vol 25 (12) ◽  
pp. 1576-1580 ◽  
Author(s):  
Ana Muntañola ◽  
Francesc Bosch ◽  
Pedro Arguis ◽  
Eduardo Arellano-Rodrigo ◽  
Carmen Ayuso ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Chronic Lymphocytic Leukemia ◽  
Early Stage ◽  
Strong Predictor ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Clinical Information ◽  
Lymphocytic Leukemia ◽  
Abdominal Ct ◽  
Work Up

Purpose Whether computed tomography (CT) should be routinely included in the diagnostic work-up in patients with chronic lymphocytic leukemia (CLL) has not yet been determined. The aim of this study was to analyze the prognostic significance of abdominal CT in patients with CLL in Rai clinical stage 0. Patients and Methods Abdominal CT was performed at diagnosis in 140 patients consecutively diagnosed with CLL in Rai stage 0 disease. Results An abnormal abdominal CT was found in 38 patients (27%). Abnormal CT correlated with increased bone marrow infiltration (P = .024), high lymphocyte count (P = .001), increased ZAP-70 expression (P = .003), and short lymphocyte doubling time (LDT; P = .007). Patients with abnormal CT progressed more frequently and had a shorter time to progression than those with normal CT (median, 3.5 years v not reached, respectively; P < .001) and required earlier treatment intervention. In a multivariate analysis, only high ZAP-70 expression (relative risk = 3.60) and an abnormal abdominal CT (RR = 2.71) correlated with disease progression. Conclusion In this series, an abnormal abdominal CT was a strong predictor of progression in patients with early-stage CLL. The inclusion of CT scans in the initial work-up of patients with early clinical stage on clinical grounds can, therefore, provide relevant clinical information.

Characteristics and Outcome of B-Cell Chronic Lymphocytic Leukemia in HCV-Positive Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4986-4986
Author(s):  
Stefano Molica ◽  
Rosanna Mirabelli ◽  
Demetrio Misuraca ◽  
Caterina Battaglia
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Absolute Lymphocyte Count ◽  
Serum Levels ◽  
Autoimmune Disorders ◽  
Lymphocytic Leukemia ◽  
Severe Infections ◽  
Hodgkin's Lymphomas ◽  
Cell Chronic Lymphocytic Leukemia

Abstract HCV-associated B-cell non-Hodgkin’s lymphomas (NHL) show distinctive clinico-pathological features such as older age, liver damage, presence of monoclonal gammopathy, increased incidence of autoimmune disorders, extranodal localizations and restricted histological subtypes. As far as B-cell chronic lymphocytic leukemia (CLL) is concerned, information dealing with either characteristics or outcome of HCV-associated CLL are limited. With this background we compared clinico-hematological features and outcome of 34 HCV-positive patients diagnosed at our institution as having immunologically typical B-cell CLL (i.e., CD5+/CD23+/CD79b-/SmIg dim) with 161 unselected CLL HCV-negative patients followed-up in the last 10 years. The two groups were alike with respect to main clinico-hematological features such as age (P=0.780), sex (P=0.650), absolute lymphocyte count (P=0.788), platelet count (P=0.362), haemoglobin level (P=0.704), β2-microglobulin (P=0.192), Binet stage distribution (P=0.224) and lymphocyte doubling time (LDT)(P= 0.620). As expected either ALT or AST serum levels at the time of CLL diagnosis were significantly higher in HCV-positive patients in comparison to HCV-negative ones (P&lt;0.0001 for both). In contrast, no difference was found in the incidence of monoclonal gammopathy between HCV-positive and HCV-negative patients (10.3% versus 7.7%; P=0.708). The same applied for autoimmune disorders which were homogeneously distributed in the two subgroups (P=0.711) and accounted, more frequently, for autoimmune emolytic anemia (AEA)(HCV-negative subgroup, 5.5%; HCV-positive subgroup, 9.0%). The proportion of severe infections registered did not reflect the HCV-status (HCV-negative subgroup, 9.6%; HCV-positive subgroup 6.4%; P= 0.510). Also second tumours were equally distributed among HCV-positive and HCV-negative subgroups (10% versus 6.8%; P=0.655). Survival curves projected at 10 years did not show any statistical in terms overall survival (Hazard Risk, 0.690; 95% CI: 0.216–1.304; P=0.167). Finally, the short term hepatic toxicity of chemotherapy did not increase among HCV-positive patients (P=0.671). In conclusion, HCV-positive patients with B-cell CLL do not differ from other patients both for presentation and clinical outcome. The need to activate specific protocols of antiviral therapy appears less urgent in comparison to NHL, however, younger CLL patients HCV-positive who are eligible for therapies at higher immunosuppressive potential (i.e., chemo-immunotherapy) should be taken in special consideration.

Global Methylation Provides Independent Prognostic Information in Chronic Lymphocytic Leukemia and Is Associated with a Microrna Signature

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3873-3873
Author(s):  
Alfons Navarro ◽  
Gerardo Ferrer ◽  
Marina Díaz-Beyá ◽  
Carmen Muñoz ◽  
Rut Tejero ◽  
...  
Keyword(s):  
Dna Methylation ◽  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Mirna Expression ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Surrogate Marker ◽  
Lymphocytic Leukemia ◽  
Prognostic Impact ◽  
Global Methylation

Abstract Abstract 3873 Introduction: Disruption of normal DNA methylation, including both gene specific hypermethylation and genome-wide hypomethylation, is found in most malignant tumors. Most epigenetic studies in chronic lymphocytic leukemia (CLL) have been focused in CpG islands and gene promoter regions, and have identified hypomethylated genes, such as BCL2 or TCL1, and hypermethylated genes, such as GRM7. However, the quantification of overall methylation measured as levels of 5-methylCytosine (5mC) has been poorly explored. As compared to their normal counterparts (CD19+ B cells), overall hypomethylation has been observed in CLL neoplastic cells. Importantly, the overall methylation varies among patients but its clinical significance has not been widely investigated. In addition, it is known that microRNA (miRNA) expression is altered in CLL, and that and epigenetic mechanisms, such as methylation, can affect miRNA expression. Aim: To investigate the prognostic impact of overall methylation in patients with CLL and to analyze the correlation of 5mC levels with miRNAs expression. Methods: We analyzed 73 CLL patients (median age, 69 [range, 34–86]; 43% males) diagnosed in our institution between 1992 and 2007. The median follow up was 10.5 years. The level of global methylation in total DNA was estimated after determination of percentage of 5mC using anti-5mC monoclonal antibodies (MethylFlash Methylated DNA Quantification Kit, Epigentek). The expression of 377 mature miRNAs was analyzed using TaqMan Array Human MicroRNA A Card v2.0 (Applied Biosystems). Statistical analysis was performed with SPSS version 15.0.1 and R software version 2.9.0. MaxStat package of R were used to determine the optimal cutoffs and Quantitative trail function in BRB array tools to correlate miRNA expression and methylation levels. Results: The analysis of methylation levels showed a wide distribution of methylation degree among patients (median: 3.02%, range: 0.58–6.14%). From the clinical standpoint, methylation levels were only correlated with Binet clinical stage, patients with C stage showing a higher degree of methylation (p=0.015). Using MaxStat, we identified two cutoffs which classified patients as having low, medium or high degree of methylation. Mean progression-free survival (PFS) was 8.4 years (95% CI: 6.4–10.4), 6.2 years (95% CI: 4.7–7.7) and 3.2 years (95% CI: 2.4–4.8) for patients with low, medium, and high methylation levels, respectively (p=0.013). In the multivariate analysis for PFS (including ZAP70, IGHV, Age≤65, cytogenetics and global methylation), high ZAP70 expression (HR: 3; 95%CI: 1.1–7.9; p=0.026) and high global methylation (HR: 5.4 95%CI: 1.7–17.1; p=0.004) were independent unfavorable prognostic factors, while a significant trend was observed for high-risk cytogenetics (17p-, 11q-, +12) (p=0.054). Interestingly, methylation levels retained its prognostic significance in subgroup analysis: clinical stage A (p=0.06) and B/C (p=0.009); mutated (p=0.008) and unmutated IGHV (p=0.028); low (p=0.028) and high ZAP70 (p=0.001); and low-risk (normal karyotype, 13q-)(p=0.008) and high-risk (17p-, 11q-, +12) cytogenetics (p=0.001). Finally, we identified a 4-miRNA signature associated with global methylation levels: miR-103 (Spearman correlation [SC]: −0.821;p=0.03), miR-132 (SC: 0.786;p=0.05), miR-494 (SC: −0.786; p=0.02), and miR-193a-5p (SC: 0.786; p=0.05). Interestingly, miR-103, miR-132 and miR-494 are located in subtelomeric regions, which are known to be more susceptible to overall methylation changes. Conclusions: In this study, the degree of global DNA methylation was an independent prognostic factor for PFS in patients with CLL. The analysis of overall methylation could be useful not only for the prognosis of patients with CLL but also in the monitoring of clinical trials in which hypomethylating agents (e.g., decitabine) are being investigated as CLL therapy. The correlation between overall methylation levels and certain miRNAs may be a surrogate marker of epigenetic lesions and deserves further investigation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals High serum levels of soluble interleukin 2 receptor in patients with B chronic lymphocytic leukemia

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 396-400 ◽  
Author(s):  
G Semenzato ◽  
R Foa ◽  
C Agostini ◽  
R Zambello ◽  
L Trentin ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Interleukin 2 ◽  
Serum Levels ◽  
High Serum ◽  
Lymphocytic Leukemia ◽  
Soluble Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interleukin 2 Receptor

Abstract By using an enzyme-linked immunosorbent assay, the presence of the soluble form of the interleukin-2 receptor (sIL-2R) was evaluated in the peripheral blood of 54 patients with B cell chronic lymphocytic leukemia (B-CLL). Serum levels of sIL-2R were correlated with clinical features, relevant hematologic and immunological data, and in some cases, with in vitro functional studies. In 51 patients (94.4%), the levels of sIL-2R were increased as compared with normal age-matched controls (1,781 U/mL +/- 231 v 276 U/mL +/- 26, respectively; P less than .001). Although this increase was observed in all stages of the disease and independently of several hematologic and immunologic parameters, a trend toward lower levels of sIL-2R was documented in patients with a less-invasive disease. When the values were correlated with the functional status of the residual T cell population, it was found that patients with the lowest levels of sIL-2R showed the best mitogenic response and helper capacity. It is suggested that in B-CLL patients the high levels of serum sIL-2R, capable of binding to its ligand, may block the T cell-produced IL-2, thus contributing toward a defective physiological action by this lymphokine. In turn, this defective availability of IL-2 may play a part in the abnormal immunoregulation that is implicated in the hypogammaglobulinemia, susceptibility to infections, and incidence of second neoplasias often observed in this disease.

Angiopoietin-2 mRNA Expression Is Elevated in Chronic Lymphocytic Leukemia Patients with Poor Prognostic Features

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4182-4182
Author(s):  
Filip Vrbacky ◽  
Lukas Smolej ◽  
Vladimira Vroblova ◽  
Sona Pekova ◽  
Monika Hrudkova ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Mononuclear Cells ◽  
Statistical Significance ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Mrna Levels ◽  
Prognostic Features ◽  
Angiopoietin 2

Abstract Several studies have demonstrated potential prognostic importance of angiogenesis in chronic lymphocytic leukemia (CLL). Elevated expression of angiogenic activator angiopoietin-2 (Ang-2) was recently reported in CLL but data regarding prognostic significance of Ang-2 in CLL is limited. Therefore, we evaluated potential relationship between Ang-2 expression and other prognostic factors in patients with CLL. Ang-2 mRNA was quantified by real-time quantitative PCR in purified mononuclear cells of 33 untreated CLL patients. Ang-2 transcript levels were further analyzed with regard to clinical stage, disease course, IgVH mutation status, CD38 and ZAP-70 expression. Elevated Ang-2 mRNA was detected in 12 cases; twenty-one patients had very low or undetectable levels of Ang-2 transcript. High Ang-2 mRNA levels were significantly associated with unmutated IgVH genes (p=0.010) and high CD38 expression (p=0.011) but not with ZAP-70 expression (p=0.784), Rai stage (p=0.305) or stable vs. progressive clinical course (p=0.443). Interestingly, there was a trend towards shorter progression-free survival in patients with high Ang-2 expression, but it did not reach statistical significance (median 15 months vs. not reached; p=0.090). In conclusion, our data show that Ang-2 mRNA is differentially expressed in patients with CLL and its increased expression appears to be associated with poor prognostic features.

scholarly journals The malignant B cells from B-chronic lymphocytic leukemia patients release TAC-soluble interleukin-2 receptors

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 447-450 ◽  
Author(s):  
NE Kay ◽  
J Burton ◽  
D Wagner ◽  
DL Nelson
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Interleukin 2 ◽  
Elevated Serum ◽  
Serum Levels ◽  
Mean Value ◽  
Lymphocytic Leukemia ◽  
Membrane Expression

Abstract Both membrane (p55) and soluble (p45) forms of TAC-reactive interleukin- 2 receptor (IL-2R) are expressed and/or released by activated lymphocytes or monocytes. Previous work has detected increased levels of circulating, TAC-soluble IL-2R (soluble TAC antigen) in the serum of most B-cell chronic lymphocytic leukemia (B-CLL) patients. We detected soluble TAC antigen in B-CLL patients (mean of 3,332 U/mL v 410 for controls). Serum soluble TAC antigen levels increased with stage (mean value of 1,187 U/mL for stage 0 v 2,527 for stage 2 and 5,410 for stages 3 and 4). We next attempted to determine whether the elevated serum levels of soluble TAC antigen in B-CLL patients might result from shedding or secretion of the receptor from the circulating, malignant B cells. Purified, malignant B cells from B-CLL patients were capable of producing easily detectable soluble TAC antigen after 48 hours of in vitro culture (range of 60 to 1,563 U/mL). IL-2R production by CLL B cells was dose dependent in most patients over a concentration of 10 x 10(6) to 60 x 10(6)/mL. In contrast, there was little or no detectable soluble TAC antigen when highly purified T cells from the same patients were cultured. Finally, despite elaboration of soluble IL-2R by CLL B cells, membrane expression of B-cell IL-2R was detected in only six of 11 patients. Thus, the cellular source of the elevated serum IL-2R levels is the malignant CLL B cell. Taken together these data suggest that (a) the malignant CLL B cell is “activated” in terms of release of soluble IL-2R and may serve as a tumor marker in this disease and (b) the elevated levels of circulating IL-2R may be an associated factor in the cellular immunodeficiency noted in B-CLL patients.

scholarly journals CD200 Baseline Serum Levels Predict Prognosis of Chronic Lymphocytic Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4239
Author(s):  
Giovanni D’Arena ◽  
Candida Vitale ◽  
Marta Coscia ◽  
Daniela Lamorte ◽  
Giuseppe Pietrantuono ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Prognostic Significance ◽  
Serum Levels ◽  
Prognostic Indicator ◽  
Lymphocytic Leukemia ◽  
Prognostic Impact ◽  
Baseline Serum ◽  
Response To Chemotherapy ◽  
Relevant Role ◽  
Time To First Treatment

Membrane-bound CD200 is overexpressed in chronic lymphocytic leukemia (CLL), and there is some evidence that its soluble ectodomain (sCD200) could also be involved in the pathophysiology and the disease. However, very little is known about sCD200’s prognostic significance. sCD200 was tested at diagnosis in 272 patients with CLL and in 78 age- and sex-matched healthy subjects using a specific human CD200 (OX-2 membrane glycoprotein) ELISA kit. A significantly higher concentration of sCD200 was found in CLL patients compared to controls. In our cohort, sCD200 was significantly higher in patients who were older than 66 years, with Binet stage C, unmutated IgVH and unfavorable (del11q or del17p) FISH. Time-to-first treatment and overall survival were significantly shorter in patients with higher sCD200 concentration, using as a cut-off 1281 pg/mL, the median value for sCD200 concentration in the whole CLL cohort. However, the prognostic impact of sCD200 was not confirmed in multivariate analysis. Baseline sCD200 values appeared to have an impact on the response to chemotherapy or chemo-immunotherapy, but not to targeted agents. Collectively, our data show that sCD200 serum levels correlate with more aggressive clinical and biological features and are able to predict a worse prognosis. This work supports the relevant role of CD200 not only as a diagnostic tool but also as a prognostic indicator and a potential therapeutic target in CLL.

scholarly journals High serum levels of soluble interleukin 2 receptor in patients with B chronic lymphocytic leukemia

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 396-400 ◽  
Author(s):  
G Semenzato ◽  
R Foa ◽  
C Agostini ◽  
R Zambello ◽  
L Trentin ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Interleukin 2 ◽  
Serum Levels ◽  
High Serum ◽  
Lymphocytic Leukemia ◽  
Soluble Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interleukin 2 Receptor

By using an enzyme-linked immunosorbent assay, the presence of the soluble form of the interleukin-2 receptor (sIL-2R) was evaluated in the peripheral blood of 54 patients with B cell chronic lymphocytic leukemia (B-CLL). Serum levels of sIL-2R were correlated with clinical features, relevant hematologic and immunological data, and in some cases, with in vitro functional studies. In 51 patients (94.4%), the levels of sIL-2R were increased as compared with normal age-matched controls (1,781 U/mL +/- 231 v 276 U/mL +/- 26, respectively; P less than .001). Although this increase was observed in all stages of the disease and independently of several hematologic and immunologic parameters, a trend toward lower levels of sIL-2R was documented in patients with a less-invasive disease. When the values were correlated with the functional status of the residual T cell population, it was found that patients with the lowest levels of sIL-2R showed the best mitogenic response and helper capacity. It is suggested that in B-CLL patients the high levels of serum sIL-2R, capable of binding to its ligand, may block the T cell-produced IL-2, thus contributing toward a defective physiological action by this lymphokine. In turn, this defective availability of IL-2 may play a part in the abnormal immunoregulation that is implicated in the hypogammaglobulinemia, susceptibility to infections, and incidence of second neoplasias often observed in this disease.

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