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Abstract: Automated morphological assessment of peripheral blood slides has become an important modality facilitating characterization and quantification of cells in a uniform, fast and robust manner. In this study, we evaluated the morphological diversity in peripheral blood films of 94 chronic lymphocytic leukemia (CLL) patients using the DM1200 CellaVision automated microscopy system. Aberrant lymphocytes and smudge cells were enumerated and correlated with CLL immunophenotype, chromosomal aberrations and prognostic parameters. Herein, we show that the percentages of aberrant and smudge cells was highly variable between patients and did not correlate with each other. Increased aberrant lymphocytes and fewer smudge cells were associated with an atypical immunophenotype including low expression of CD23, higher levels of FMC7 and bright surface levels of CD20. High fraction of aberrant lymphocytes also was associated with trisomy 12. These cells were predominantly of small/medium size, sometimes with cleft nuclei. No correlation was noted between aberrant or smudge cells and clinical stage, CD38, ZA70 or time to first treatment. Taken together, automated morphological analysis of peripheral blood leukocytes emerged as a powerful and robust tool for the quantitative morphological stratification of CLL. Integration of the automated morphological features discriminates between different CLL phenotypes and distinct chromosomal aberrations. [Copyright &y& Elsevier]

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, CD4CD39 lymphocytes were increased in the peripheral blood of patients with CLL and correlated with the advanced stage of disease. CD4CD39 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 CD4CD39 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. [ABSTRACT FROM AUTHOR]