Adhesion molecule expression in CD5-negative/CD10-negative chronic B-cell leukemias: Comparison with non-Hodgkin's lymphomas and CD5-positive B-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<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.

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Serum Insulinlike Growth Factor Is Not Elevated in Patients with Early B-Cell Chronic Lymphocytic Leukemia but Is Still a Prognostic Factor for Disease-Progression.

Blood ◽

10.1182/blood.v104.11.4786.4786 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4786-4786

Author(s):

Stefano Molica ◽

Gaetano Vitelli ◽

Rosanna Mirabelli ◽

Giovanna Digiesu ◽

Diana Giannarelli ◽

...

Keyword(s):

Cell Adhesion ◽

Growth Factor ◽

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Disease Progression ◽

Adhesion Molecule ◽

Serum Levels ◽

Lymphocytic Leukemia ◽

Cell Chronic Lymphocytic Leukemia ◽

Igfbp 3

Abstract Insulin like growth factor 1 (IGF-1) is an important growth and antiapoptotic factor for the cancer cells in several malignancies and in multiple myeloma recent studies support the hypotesis of a role for IGF-1 in disease progression. Clinico-biological relevance of IGF-1 was never studied in B-cell chronic lymphocytic leukemia (CLL). Using a quantitative sandwich immunoassay technique (ELISA)(QUANTIKINE®, Human IGF-1 and IGFBP-3, R & D Systems), we measured the concentration of IGF-1 and its major binding protein IGF-binding protein 3 (IGFBP-3) in serum drawn at the time of diagnosis from 77 Binet stage A CLL patients. Either IGF-1 or IGFBP-3 were significantly decreased compared to healthy age- and sex-matched controls (P<0.0001 for both; Mann-Whitney test). Serum levels of IGF-1 and IGFBP-3 paralleled each other (P=0.002); in contrast, no significant correlation was found between serum levels of IGF-1 and clinico-hematological variables including age (P=0.253), sex (P=0.270), Rai clinical substages (P=0.140), LDH (P=0.956), β2-microglobulin (P=0.368), lymphocyte count (P=0.703) and lymphocyte doubling time [LDT](P=0.233). When correlation were attempted with circulating levels of angiogenic cytokines such as vascular endothelial growth factor (VEGF)(P=0.971), basic fibroblastic growth factor (FGF-2)(P=0.695), angiogenin (P=0.282) or adhesion molecules such as vascular cell adhesion molecule-1 [VCAM-1] (P=0.318), intercellular adhesion molecule-1 [ICAM-1] (P=0.883) and platelet endothelial cell adhesion-1 [PECAM-1] (P=0.772) similar results were found. Serum levels of IGF-1 were further evaluated as a dichotomous variable with respect to progression-free survival (PFS), an endpoint surrogate for overall survival in early B-cell CLL. The best separation of curves was seen with the cutoff point at the 75th percentile of IGF-1 levels (i.e., 93 pg/ml). Median PFS was 63 months in the patient group with low IGF-1, compared to a median PFS of 40 months in the remaining patients (P=0.002; HR, 0.311, 95% C.I, 0.085–0.630). In the multivariate analysis performed including variables significant at univariate analysis [i.e., Rai substage (P=0.002); LDT (P=0.004), IGF-1 (P=0.01)], only Rai substage retained prognostic significance (P=0.006). However, after removing from analysis LDT (only 6 out of 77 had an LDT< 12 months), either IGF-1 or Rai substage entered the model at a significant level ((P=0.03 and P=0.01, respectively). In conclusion, IGF-1 did not correlate with markers of tumor burden or clinical status in CLL thus suggesting that levels of this cytokine do not reflect the intrinsic malignancy of disease. Results of the present study highlight, however, its involvement in mechanisms of disease-progression in early CLL.

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Soluble intercellular adhesion molecule-1 correlates with markers of disease activity in B-cell chronic lymphocytic leukemia [letter; comment]

Blood ◽

10.1182/blood.v85.8.2280.bloodjournal8582280 ◽

1995 ◽

Vol 85 (8) ◽

pp. 2280-2281

Author(s):

S Molica ◽

A Dattilo ◽

A Mannella ◽

D Levato ◽

P Musto ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Disease Activity ◽

B Cell ◽

Adhesion Molecule ◽

Lymphocytic Leukemia ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Letter Comment ◽

Soluble Intercellular Adhesion Molecule ◽

Cell Chronic Lymphocytic Leukemia

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Expression on leukemic cells and serum circulating levels of intercellular adhesion molecule-1 (ICAM-1) in B-cell chronic lymphocytic leukemia: Implications for prognosis

Leukemia Research ◽

10.1016/0145-2126(95)00017-i ◽

1995 ◽

Vol 19 (8) ◽

pp. 573-580 ◽

Cited By ~ 9

Author(s):

Stefano Molica ◽

Angela Dattilo ◽

Ada Mannella ◽

Domenico Levato ◽

Luciano Levato

Keyword(s):

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Adhesion Molecule ◽

Intercellular Adhesion ◽

Lymphocytic Leukemia ◽

Leukemic Cells ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Circulating Levels ◽

Cell Chronic Lymphocytic Leukemia

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Adhesion molecule expression on B-cell chronic lymphocytic leukemia cells: malignant cell phenotypes define distinct disease subsets

Blood ◽

10.1182/blood.v81.10.2679.2679 ◽

1993 ◽

Vol 81 (10) ◽

pp. 2679-2687 ◽

Cited By ~ 57

Author(s):

G De Rossi ◽

D Zarcone ◽

F Mauro ◽

G Cerruti ◽

C Tenca ◽

...

Keyword(s):

Bone Marrow ◽

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Adhesion Molecules ◽

Adhesion Molecule ◽

Lymphocytic Leukemia ◽

Leukemic Cells ◽

Distinct Disease ◽

Beta 2 ◽

Cell Chronic Lymphocytic Leukemia

Abstract Expression of surface adhesion molecules of the Ig superfamily (CD54 and CD58), of the integrin family (beta 1, beta 2, and beta 3 chains), of the selectin family (L-selectin), and of the lymphocyte homing receptor (CD44) was analyzed on B-cell chronic lymphocytic leukemia (B- CLL) cells from 74 patients. The aim of the study was the definition of phenotypically distinct disease subsets and the correlation of adhesion molecule phenotypes with clinical parameters. Expression of CD58 on B- CLL cells defined more advanced disease stages. In comparison with beta chain-positive cases, patients whose cells did not express beta 1, beta 2, and beta 3 integrin chains fell into the most favorable prognostic group, with lower lymphocytosis and the absence of splenomegaly, diffuse bone marrow infiltration, and therapy requirement. A novel finding was the expression of beta 3 chains on cells from a minority (12 of 74) of B-CLL cases. beta 3 chains were always coexpressed with beta 1 and beta 2 chains. Two-color immunofluorescence analyses of adhesion molecules such as alpha x beta 2 integrin (LeuM5) and L- selectin (Leu8) showed that these markers were detectable on variable proportions of leukemic cells, thus confirming the intraclonal phenotypic heterogeneity of B-CLL. Differences in the intensity of CD44 expression were also shown among the various B-CLL clones. Finally, no major variations were shown by comparison of adhesion molecule phenotypes of leukemic cells simultaneously obtained from blood and bone marrow, and of CD5+ versus CD5- clones.

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Adhesion molecule expression on B-cell chronic lymphocytic leukemia cells: malignant cell phenotypes define distinct disease subsets

Blood ◽

10.1182/blood.v81.10.2679.bloodjournal81102679 ◽

1993 ◽

Vol 81 (10) ◽

pp. 2679-2687 ◽

Cited By ~ 1

Author(s):

G De Rossi ◽

D Zarcone ◽

F Mauro ◽

G Cerruti ◽

C Tenca ◽

...

Keyword(s):

Bone Marrow ◽

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Adhesion Molecules ◽

Adhesion Molecule ◽

Lymphocytic Leukemia ◽

Leukemic Cells ◽

Distinct Disease ◽

Beta 2 ◽

Cell Chronic Lymphocytic Leukemia

Expression of surface adhesion molecules of the Ig superfamily (CD54 and CD58), of the integrin family (beta 1, beta 2, and beta 3 chains), of the selectin family (L-selectin), and of the lymphocyte homing receptor (CD44) was analyzed on B-cell chronic lymphocytic leukemia (B- CLL) cells from 74 patients. The aim of the study was the definition of phenotypically distinct disease subsets and the correlation of adhesion molecule phenotypes with clinical parameters. Expression of CD58 on B- CLL cells defined more advanced disease stages. In comparison with beta chain-positive cases, patients whose cells did not express beta 1, beta 2, and beta 3 integrin chains fell into the most favorable prognostic group, with lower lymphocytosis and the absence of splenomegaly, diffuse bone marrow infiltration, and therapy requirement. A novel finding was the expression of beta 3 chains on cells from a minority (12 of 74) of B-CLL cases. beta 3 chains were always coexpressed with beta 1 and beta 2 chains. Two-color immunofluorescence analyses of adhesion molecules such as alpha x beta 2 integrin (LeuM5) and L- selectin (Leu8) showed that these markers were detectable on variable proportions of leukemic cells, thus confirming the intraclonal phenotypic heterogeneity of B-CLL. Differences in the intensity of CD44 expression were also shown among the various B-CLL clones. Finally, no major variations were shown by comparison of adhesion molecule phenotypes of leukemic cells simultaneously obtained from blood and bone marrow, and of CD5+ versus CD5- clones.

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