The CD31 antigen is expressed by a variety of cells including B lymphocytes from patients with B-CLL. The CD31 gene is polymorphic and CD31 gene polymorphisms involving single nucleotide substitutions (SNPs) such as C+373G (Leu125Val) and G+1688A (Ser563Asn) have been implicated in the pathogenesis of a number of diseases. CD31 is the physiological ligand for the CD38, a powerfull and independent prognostic marker for patients with B-CLL. A recent published study reports that the percentage of CD31 expression does not predict for poor prognosis in B-CLL (

Ibrahim S, et al. Cancer. 2003;97:1914–1918
). A previous study showed that quantification of CD38 expression by flow cytometry significantly improves its prognostic value (
Mainou-Fowler T, et al. Br J Haematol. 2002;118:755–761
). To re-assess the predictive power of CD31 in B-CLL, we quantified its expression and correlated its intensity with clinical outcome in a cohort of 120 patients (70M, 50F, age 47–91). The role in B-CLL of CD31 SNPs was also examined.

We report that Binet stage A patients had a significantly higher density of CD31 compared with stage B/C patients. A low CD31 predicted for poor disease outcome and identified those Binet stage A patients, and patients with low CD38, who followed a more aggressive clinical course. Disease-specific survival of patients with both low CD31 and high CD38 was significantly shorter than all other groups. Low CD31 expression significantly related with the homozygous GG and AA genotypes of the Leu125Val and Ser563Asn polymorphisms, respectively. The alleles found to be in strong disequilibrium but this was not 100%. There was no significant difference between observed and expected allele frequencies and no significant association was observed between patient genotype and clinical outcome.

Statistical comparisons are as follows: All patients:

  • survival:

    1. high CD31 vs low CD31: P=0.0087,

    2. high CD31, low CD38 vs low CD31, low CD38: P=0.0425,

    3. low CD31, low CD38 vs low CD31, high CD38: P=0.0013,

  • time to treatment: high CD31 vs low CD31: P=0.0064.

In stage A patients:

    1. P=0.0353,

    2. P=0.0721,

    3. P=0.0214,

  • P=0.0716.

Distribution of CD31 expression within the genotypes: Leu/Leu vs Leu/Val, P=0.1442; Leu/Leu vs Val/Val, P=0.0466; Leu/Val vs Val/Val, P=0.0466; Asn/Asn vs Asn/Ser, P=0.1850; Asn/Asn vs Ser/Ser, P=0.0251; Asn/Ser vs Ser/Ser, P=0.0439.

In conclusion, low level of CD31 expression is an adverse prognostic indicator in B-CLL. The role of CD31 SNPs in B-CLL requires further investigation.

Topics:
cd31 antigens, chronic b-cell leukemias, chronic lymphocytic leukemia, genes, polymorphism, balance impairment, cancer, flow cytometry, ligands, nucleotides

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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