Peripheral blood lymphocytes from patients with chronic lymphocytic leukemia (CLL) had diminished and/or delayed in vitro responses to both phytohemagglutinin (PHA) and concanavalin A (Con A) as determined by thymidine incorporation into DNA, over a 9-day incubation period. The cytoarchitectural features of CLL lymphocytes stimulated by each of the mitogens were similar to those observed in transformed normal cells. However, as shown by planimetric measurements, the mean cell area and the nuclear, cytoplasmic, and mitochondrial areas were diminished in comparison to PHA-stimulated normal cells. The data suggest that some CLL lymphocytes which transform with PHA or Con A are residual normal thymus-dependent (T) lymphocytes, and others may be derived from the metabolically defective leukemic cell population

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