The expression of CD73 on pathological B-cells is associated with shorter overall survival of patients with CLL.

CD73 is a membrane-bound enzyme that catalyzes the extracellular conversion of adenosine monophosphate to adenosine. Adenosine is thought to play a role in promoting tumor growth and survival together with suppressing the host immune responses, which contribute to the multistep process of tumorigenesis. Here, we studied the expression of this antigen in chronic lymphocytic leukemia (CLL). The expression of CD73 was analyzed by multiparametric flow cytometry on normal and pathological B-cells from peripheral blood and bone marrow samples from 71 patients with CLL. Pathological B-cells expressed significantly lower levels of CD73 than normal B-cells (p<0.01). Patients with splenomegaly showed a higher expression of CD73 on pathological B-cells than patients without splenomegaly (p<0.05). The expression of CD73 also correlated with beta-2-microglobulin levels (p<0.05). Clinically, patients with higher levels of CD73 versus those with lower expression presented with shorter overall survival (median OS of 65 vs. 113 months, p<0.05). Our data indicate that CD73 may play a role in CLL pathophysiology, is correlated with poor clinical and biological prognostic factors and may be of potential value as a prognostic marker and therapeutic target.

Cytogenetic abnormalities predict treatment-free interval and response to therapy in previously untreated chronic lymphocytic leukemia patients.

We evaluated the prognostic impact of chromosomal abnormalities as detected by interphase fluorescence in situ hybridization (iFISH) in 86 chronic lymphocytic leukemia (CLL) patients. Overall, 39 of 86 (45%) patients displayed one (35%) or more (10%) chromosomal abnormalities, del13q (31%) being more frequently detected than trisomy 12 (19%) followed by del11q (17%), del17p (6%) and del6q (5%). Significant differences in the treatment free intervals (TFIs) were observed among individual cytogenetic subgroups (p=0.027) with the shortest mean TFIs in subgroups with del17p, del11q and trisomy 12 (10, 12 and 14 months, respectively) as compared to subgroups with normal cytogenetics (38 months) and del13q (68 months). Poor response to therapy was observed in subgroups with del11q (p=0.044) and trisomy 12 (p=0.047) while patients with normal cytogenetics had good response (p=0.003). Furthermore, del17p and del11q were associated with highest tumor burden and disease activity as reflected by corresponding laboratory data.