Functional characterization of the cells in chronic neutrophilic leukemia

Abstract

Light and electron microscopy of neutrophils from chronic neutrophilic leukemia (CNL) did not reveal differences from normal mature neutrophils. However, functional characterization of CNL cells showed marked differences when compared to normal cells. CNL neutrophils were much less viable in suboptimal conditions. Their survival was further reduced by autologous serum and was corrected by normal human serm. CNL cells showed very active phagocytosis, but their bactericidal activity was reduced in suboptimal conditions. The total content of lysozyme and beta-glucuronidase was lower in CNL cells compared to normal neutrophils, but the release of these enzymes from stimulated cells was much higher than normal. This observation is compatible with a marked lysosomal lability. Cells from the patients' peripheral blood and bone marrow showed excessive growth in CFU-C assays. Marked susceptibility of CNL cells to cytotoxic activity of cold agglutinins, SLE sera, and CSFs was observed and may signify qualitative and/or quantitative differences in the membrane structure of CNL neutrophils, as compared to normal cells.

Neutrophil Function in Chronic Neutrophilic Leukemia: Defective Respiratory Burst in Response to Phorbol Esters

“…Published studies of neutrophil function in CNL have been limited to one or two cases each. Dotten et al [3] reported normal phagocytosis, slightly decreased bacterial killing and increased granule release in response to immune complexes. Kaplan and Chervenick [7] also ob served slightly decreased bacterial killing but found the metabolic burst to be normal to a phagocytic stimulus, confirming earlier results [4].…”

Cellular Abnormalities and Reduced Colony-Forming Cells in Chronic Neutrophilic Leukaemia

“…Patients with other MPD often have haemor rhagic complications and since the majority of these patients are middle-aged or older, they may require medication for back pain and joint problems, which could interfere with the platelet function and aggra vate the bleeding tendency. 5 of the 17 CNL patients reported previously have died due to a bacterial infection [1,3,14], Although our patient has never had an infective process, the neutrophils showed active phagocytosis, but intracel lular killing was reduced. Abnormalities of neutrophil granules described which predispose patients to in fections include lactoferrin deficiency due to absence of specific granules [15] and peroxidase deficiency with absence of or abnormal depletion of azurophil granules [16], It could be speculated that this may be the cause of serious infections in CNL.…”

“…In 1 case the attempt was made so close to the onset of blast transformation that failure might be due to the development of the acute phase [4], In another case three attempts to culture bone marrow during a 16-month period, prior to the development of blast crises, was unsuccessful [5] but in a further case CNL cells grew easily [3]. In our patient peripheral blood tested twice at a 6-month interval and bone marrow tested once all showed reduced numbers of CFU-C.…”

“…The functional characteristics of CNL cells have been studied in 1 case [3] and attempts to grow these cells in culture have been unsuccessful in 2 cases [4,5], while excessive growth was reported in 1 case [3]. There is a significant haemorrhagic tendency [1,6] and bleeding has been the cause of death in 2 pa tients.…”

A Case of Chronic Neutrophilic Leukemia with Multiple Myeloma and an Increased Function of Her Neutrophils

“…4) In this case, phagocytosis, chemotaxis and respiratory burst activity (superoxide production) were increased, especially in the absence of stimulation (spontaneous respiratory burst activity), whereas microbial killing activity was similar to that of normal control neutrophils. Normal or elevated phagocytosis and respiratory burst activity [5][6][7][8] and decreased bactericidal activity of neutrophils 4,6,7) have been reported in patients with CNL. Differences in neutrophil function may be due to differences in the pathophysiology of each patient or to technical differences in the assessment of neutrophil function.…”