Chava Perry

Chronic lymphocytic leukemia (CLL) cells depend on their microenvironment for proliferation and survival. Ectonucleotidase CD39 has anti-inflammatory properties as it hydrolyzes proinflammatory extracellular ATP, generates anti-inflammatory adenosine, and also protects regulatory T cells from ATP-induced cell death. In this study, we investigated the clinical significance of CD39 expression on CD4⁺ T cells in 62 patients with CLL as well as its compartmental regulation and explored the possible mechanisms for its induction. Compared to healthy individuals, CD4⁺CD39⁺ lymphocytes were increased in the peripheral blood of patients with CLL and correlated with the advanced stage of disease. CD4⁺CD39⁺ cells were also higher in patients with CLL, who needed therapeutic intervention, and in those who had unmutated immunoglobulin heavy chain variable region gene, were ZAP70⁺ or had β2-microglobulin levels of >3 g/L. There were more CD4⁺CD39⁺ lymphocytes in the bone marrow compartment than in the peripheral blood, and in vitro studies showed that CD39 can be induced on CD4⁺ cells by exposure to ATP or indirectly, following B cell receptor engagement. This may support the notion that the leukemic cells contribute to create an immune-subversive environment, and perhaps to a poorer prognosis. CD39⁺ may also serve as a future target for the development of novel therapies with immune-modulating antitumor agents in CLL.

Background:  ¹⁸Fluoro‐2‐deoxyglucose (¹⁸FDG) positron emission tomography (PET) is widely used for initial staging and follow‐up in patients with malignant lymphoma. While earlier studies suggested a limited role for PET in extranodal marginal zone mucosa‐associated lymphoid tissue (MALT) lymphoma patients due to their non‐FDG avidity, more recent reports have suggested that the issue is controversial. In the present study, we evaluated the diagnostic accuracy of PET integrated with CT (PETCT) in patients with MALT lymphoma and assessed its reliability in clinical staging and monitoring response.Methods:  Thirty‐three patients with biopsy proven MALT lymphoma in 37 sites, who underwent PET/CT at diagnosis, were enrolled. Medical records, PET/CT findings and data obtained by other diagnostic procedures were reviewed.Results:  Common sites of MALT lymphoma were the stomach (18), lung (5), orbit (4), and parotid gland (3). PET/CT detected active disease in 18 of 33 patients (54.5%) at diagnosis. Sensitivity in gastric MALT (38.9%) was lower when compared with non‐gastric MALT (75%). PET/CT detected active disease in 100% patients with advanced disease (stage III–IV) but only in 42.3% with early stage disease (I–II). The incidence of gastric FDG uptake was higher in patients showing gastric ulcer on gastroscopy than in subjects with minimal or no macroscopic findings. Of the 33 patients in the study cohort, 12 had a follow‐up PET/CT which detected relapse in three patients.Conclusions:  These data suggest that PET/CT is a useful tool for both, initial staging and follow‐up after therapy in patients with MALT lymphoma. Its sensitivity depends on disease location and stage at initial diagnosis.