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

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.

Download Full-text

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.

Download Full-text

Metformin Sensitizes Leukemic Cells to Cytotoxic Lymphocytes by Increasing Expression of Intercellular Adhesion Molecule-1 (ICAM-1)

10.21203/rs.3.rs-830815/v2 ◽

2021 ◽

Author(s):

Nerea Allende-Vega ◽

Joaquin Marco Brualla ◽

Paolo Falvo ◽

Catherine Alexia ◽

Michael Constantinides ◽

...

Keyword(s):

Tumor Cells ◽

Adhesion Molecule ◽

Tumor Antigens ◽

Intercellular Adhesion ◽

Leukemic Cells ◽

Intercellular Adhesion Molecule ◽

Cytotoxic Lymphocytes ◽

Lymphocyte Function ◽

Intercellular Adhesion Molecule 1 ◽

Cytotoxic Lymphocyte

Abstract Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

Download Full-text

Prognostic significance of immunoglobulin phenotype in B cell chronic lymphocytic leukemia

Blood ◽

10.1182/blood.v65.2.340.340 ◽

1985 ◽

Vol 65 (2) ◽

pp. 340-344 ◽

Cited By ~ 33

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.

Download Full-text

House Dust Mite Induces Expression of Intercellular Adhesion Molecule-1 in EoL-1 Human Eosinophilic Leukemic Cells

Journal of Korean Medical Science ◽

10.3346/jkms.2007.22.5.815 ◽

2007 ◽

Vol 22 (5) ◽

pp. 815 ◽

Cited By ~ 4

Author(s):

Byoung Chul Kwon ◽

Myung Hyun Sohn ◽

Kyung Won Kim ◽

Eun Soo Kim ◽

Kyu-Earn Kim ◽

...

Keyword(s):

Adhesion Molecule ◽

House Dust ◽

House Dust Mite ◽

Intercellular Adhesion ◽

Leukemic Cells ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Dust Mite

Download Full-text

Pro-apoptotic properties of hyperforin in leukemic cells from patients with B-cell chronic lymphocytic leukemia

Leukemia ◽

10.1038/sj.leu.2404098 ◽

2006 ◽

Vol 20 (3) ◽

pp. 491-497 ◽

Cited By ~ 33

Author(s):

C Quiney ◽

C Billard ◽

A M Faussat ◽

C Salanoubat ◽

A Ensaf ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Lymphocytic Leukemia ◽

Leukemic Cells ◽

Cell Chronic Lymphocytic Leukemia

Download Full-text

Superagonistic Anti-CD28 Antibody TGN1412 as a Potential Immunotherapeutic for the Treatment of B Cell Chronic Lymphocytic Leukemia.

Blood ◽

10.1182/blood.v104.11.2519.2519 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2519-2519 ◽

Cited By ~ 1

Author(s):

Chia-Huey Lin ◽

Thomas Kerkau ◽

Christine Guntermann ◽

Martin Trischler ◽

Niklas Beyersdorf ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Mhc Class Ii ◽

T Cell Activation ◽

Lymphocytic Leukemia ◽

Leukemic Cells ◽

Activation Markers ◽

Cell Chronic Lymphocytic Leukemia

Abstract B cell chronic lymphocytic leukemia (B-CLL) is characterised by an accumulation of malignant B cells, and impaired humoral and cellular immune responses. Evasion strategies of leukemic cells appear to involve down-regulation of co-stimulatory molecules as well as increased resistance to apoptosis. Here we provide data supporting a novel concept to treat B-CLL with a humanized, superagonistic monoclonal antibody specific for CD28 (TGN1412). Superagonistic anti-CD28 antibodies have been shown to activate human T cells in vitro without requirement for engagement of the T cell antigen receptor (Luhder et al., J. Exp. Med. 2003. 197(8):955–66). Indicative of their activation, TGN1412-triggered T cells from healthy donors upregulate, among other activation markers, CD40L, that has been reported to promote anti-leukemic effects when ectopically expressed on B-CLL cells (Wierda et al., Blood. 2000. 96 (9): 2917–2924). In this report, the responses of PBMCs from B-CLL patients to soluble TGN1412 were examined. We show that in a dose-dependent fashion, polyclonal T cell activation was induced by TGN1412 including proliferation, cytokine production and induction of activation markers such as CD25, CD71, CD134 (Ox40), CTLA-4 (CD152) and CD154 (CD40L). Significantly, modulation of malignant B-CLL cells was also observed. MHC class II molecules (HLA-DR), CD95 and the co-stimulatory molecules CD80 and CD86, but not the proliferation marker Ki-67, were strongly up-regulated upon TGN1412 stimulation. These data suggested that improved antigen-presenting functions of B-CLL cells were induced by TGN1412. Accordingly, preliminary data indicate that B-CLL cells isolated from TGN1412 stimulated cultures induced enhanced proliferation of both allogeneic and autologous T cells, and importantly, TGN1412 activated T cells exhibited enhanced CTL-activity against B-CLL cells. In conclusion, our data suggest that TGN1412 induces polyclonal T cell expansion and activation as well as increased APC function of B-CLL cells. They imply that TGN1412 may have future therapeutic benefit for B-CLL patients.

Download Full-text