Clinical significance of LAIR1 (CD305) as assessed by flow cytometry in a prospective series of patients with chronic lymphocytic leukemia

Most patients affected by chronic lymphocytic leukemia are diagnosed by flow cytometry. Severalimmunophenotypic markers have been identified as significant and independent prognosticvariables, especially from retrospective cohorts. However, while attractive because inexpensiveand feasible in most laboratories, only few were validated by independent series.The expression of LAIR1 (also known as LAIR-1 or CD305), an inhibitor of B-cell receptor -mediated signaling, has been reported to lack in high-risk chronic lymphocytic leukemia. However,its correlation with biological variables and its prognostic significance remain unknown.We investigated 311 consecutive patients, prospectively enrolled since 2007. Methods for studyingpatients were standardized and included clinical assessment, immunophenotype, fluorescence insitu hybridization, and immunoglobulin heavy chain variable region genes status. Overall, 22.1% ofpatients had Binet B or C stage, 38.5% were unmutated, 15.1% had high risk cytogeneticabnormalities, 23.4% were CD38+, 37.8% CD49d+, and 59.8% LAIR1+. Expression of LAIR1 wasinversely related to CD38 (p=0.0005), but was not associated to CD49d expression (p=0.96). Asignificantly lower expression of LAIR1 was observed in patients with B or C Binet stage (p=0.023),and in the presence of high risk cytogenetic abnormalities (p=0.048) or unmutated immunoglobulinheavy chain variable region (p<0.0001). At univariate analysis LAIR1+ was significantly associatedwith longer time to first treatment (p=0.0002). This favorable effect of LAIR1+ was confirmed bymultivariate analysis (Hazard Ratio=2.1, p=0.03 for LAIR1).Our results support LAIR1 expression as a reliable and inexpensive marker to independentlypredict time to first treatment in newly diagnosed unselected patients with chronic lymphocyticleukemia.