The LPL/ADAM29 expression ratio is a novel prognosis indicator in chronic lymphocytic leukemia

Although the zeta-associated protein of 70 kDa (ZAP-70) is overexpressed in patients with chronic lymphocytic leukemia (CLL) displaying unmutated IGVH genes and poor prognosis, a previous microarray study from our group identified overexpression of LPL and ADAM29 genes among unmutated and mutated CLL, respectively. To assess the prognostic value of these genes, we quantified their expression by real-time quantitative polymerase chain reaction (PCR) in a cohort of 127 patients with CLL and correlated this with clinical outcome, IGVH mutational status, and ZAP-70 protein expression. IGVH mutational status, ZAP-70, and the LPL and ADAM29 mRNA ratios (L/A ratio) were predictive of event-free survival for the whole cohort and for patients with stage A disease. in patients in stage B and C, the L/A ratio was an independent prognostic factor, whereas ZAP-70 did not predict survival. Simultaneous usage of the L/A ratio and ZAP-70 expression allowed an almost perfect (99%) assessment of the IGVH status in the 80% of patients with concordant results (L/A(+), ZAP-70(+) or L/A(-), ZAP-70(-)). LPL and ADAM29 gene expression could also be determined by a simple competitive multiplex reverse transcription PCR assay. Overall, quantification of LPL and ADAM29 gene expression is a strong prognostic indicator in CLL, providing better prognostic assessment than ZAP-70 in advanced stages of the disease.Hop La Pitie Salpetriere, Serv Hematol Biol, F-75013 Paris, FranceInst Pasteur, Unite Immunohematol & Immunopathol, F-75724 Paris, FranceUniversidade Federal de São Paulo, Disciplina Hematol & Hemoterapia, São Paulo, BrazilInst Pasteur, Dept Ecosyst & Epidemiol Malad Infect, Paris, FranceHop La Pitie Salpetriere, Serv Immunol, Paris, FranceInst Pasteur, Ctr Rech Vaccinale & Biomed, Paris, FranceUniversidade Federal de São Paulo, Disciplina Hematol & Hemoterapia, São Paulo, BrazilWeb of Scienc

Molecular Biomarkers for the Diagnosis of Primary Vitreoretinal Lymphoma

Primary vitreoretinal lymphoma (PVRL) or primary intraocular lymphoma, a subtype of primary central nervous system lymphoma, often masquerades as uveitis. The diagnosis of PVRL requires identification of lymphoma cells inside the eye, which is often challenging due to the frequent necrosis and admixing of PVRL cells with reactive lymphocytes. Therefore, detection of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements provide molecular diagnosis of B- and T-cell lymphoma, respectively. We retrospectively evaluated 208 cases with a clinical diagnosis of masquerade syndrome from 1998 to 2010. In 200 cases with molecular analyses using microdissection and polymerase chain reaction, we found that 110 cases had IgH gene rearrangement, 5 cases had TCR gene rearrangement, and 85 cases were negative for these two gene arrangements. The molecular data corroborated the cytopathological diagnoses of PVRL and uveitis in the majority of cases. Cytokine above the detected levels in the specimens were also measured in 80 of the 208 cases. A ratio of vitreous IL-10 to IL-6 greater than 1, suggesting PVRL, was found in 56/80 cases; 53/56 had the correct diagnosis. A ratio less than 1, suggesting uveitis, was found in 24/80 cases; 17/24 correctly confirmed the diagnosis. Moreover, the molecular data corresponded well with the clinical course of the diseases. The sensitivity and specificity of these molecular biomarkers for the diagnosis of PVRL are higher than 95%

Prognostic importance of serum soluble CD23 level in chronic lymphocytic leukemia

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