B-cell chronic lymphocytic leukemia (B-CLL) is a heterogenous disease with a highly variable clinical course. Recent studies have shown that CD38 surface expression on the malignant cell clone may serve as a prognostic marker in that CD38 ؉ patients with B-CLL are characterized by advanced disease stage, lesser responsiveness to chemotherapy, and shorter survival than CD38 ؊ patients. To further investigate the molecular phenotype of these 2 clinical subgroups, we compared the gene expression profiles of CD38 ؉ (n ‫؍‬ 25) with CD38 ؊ (n ‫؍‬ 45) B-CLL patients using oligonucleotide-based DNA chip microarrays representative of approximately 5600 genes. The results showed that B-CLLs display a common gene expression profile that is largely independent of CD38 expression. Nonetheless, the expression of 14 genes differed significantly between the 2 groups, including genes that are involved in the regulation of cell survival. Furthermore, unsupervised hierarchical cluster analysis of 76 B-CLL samples led to the separation of 2 major subgroups, comprising 20 and 56 patients. Clustering to the smaller group was due in part to the coordinate high expression of a large number of ribosomal and other translation-associated genes, including elongation factors. Importantly, we found that patients with high expression of translation factors were characterized by a more favorable clinical course with significantly longer progression-free survival and reduced chemotherapy requirements than the remaining patients (P < .05). Our data show that gene expression profiling can help identify B-CLL subtypes with different clinical characteristics. Furthermore, our results suggest a role of translationassociated genes in the pathogenesis of

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Serum Free Light Chains (FLC) have prognostic significance in diverse plasma cell dyscrasias. Although monoclonal protein secretion is a typical feature of these diseases, it can also be detected in other B cell malignancies including chronic lymphocytic leukemia. Recent data suggests a significant correlation between abnormal ratio of FLC and outcome. Therefore, we investigated the role of FLC in a large cohort of 135 patients and the correlation to immunofixation (IF) and flow cytometry. Abnormal FLC ratios were found in 78 patients (58%) whereas the IF was positive in only 32 cases (24%). In 55 cases the FLC ratio was positive while IF was negative and in only 9 cases IF was positive while the FLC ratio was normal. In 52 of 98 patients (53%) light chain restriction determined by flow cytometry was concordant with the monoclonal FLC whereas in 5 patients they did not agree. In 41 of 98 patients (42%) a normal ratio of FLC was observed while the immunophenotype was positive for lambda or kappa. Patients with an abnormal FLC ratio for lambda had a significantly shorter time to first therapy (TFT) than patients with an abnormal ratio for kappa FLC or with a normal FLC ratio (median TFT: 34 versus 76 versus 88 months, p for trend=0.039). Additionally, monoclonal FLC had a significantly shorter time to first treatment compared to polyclonal normal and abnormal FLC ratios (p for trend=0.0489). As expected, polyclonal sFLC correlated significantly with normal and abnormal serum-creatinine (p<0.0001). Future studies are warranted to elucidate the role of FLC as biomarkers of disease and as a prognostic factor for response. Patients and Methods Study population and CLL patients Between 1999 and 2011, 135 patients with B-CLL were enrolled in this retrospective analysis and analyzed with regard to several biological and clinical characteristics: Binet stage, age, gender, CD38 and ZAP-70 status, IGHV status, β2-microglobulin, time from diagnosis to first treatment and overall survival. The diagnosis of B-CLL required a persistent B cell lymphocytosis of more than 5.0×10 9 /l and a typical CD19+, CD20+ CD5+, CD23+, Ig light chain (κ or λ light chain) restricted immunophenotype as revealed by flow cytometry of peripheral blood cells. Comprehensive clinical information including treatment histories was available for all patients. Patient selection was based on the availability of cryopreserved plasma samples in our CLL cell bank collected at the time before the initiation of therapy or six months after finishing therapy. Standard clinical criteria were used for the initiation of chemotherapy [13]. CD38 and ZAP-70 expression were determined by flow cytometry as recently described [14,15]. In Table 1 the clinical and laboratory data are shown.