Jagadish S. Nadkarni

Summary An exceptional Burkitt lymphoma patient, a 16-year-old boy, yielded tumor biopsy cells and derived tissue culture lines that displayed a strong surface accumulation of IgM heavy and kappa light chain specificities judged by direct membrane fluorescence and cytotoxicity tests. This property was maintained unchanged in the course of more than 5 months of serial passage in vitro . A fourth biopsy, obtained from the patient after massive necrosis had been induced in the tumor by cytosine arabinoside chemotherapy, did not show this property at either the biopsy stage or in the derived cell line. The possibility that the neoplastic transformation of lymphoid cells may have afflicted a cell specialized to carry immunoglobulin on its surface may be considered. The phenomenon has to be distinguished from immunoglobulin coating in vivo seen with certain biopsy samples from this and other patients. The latter type of coating can be of IgM, IgG, or IgA nature and disappears rapidly on cultivation in vitro .

Interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), primarily monocyte-derived cytokines, form a group of proinflammatory cytokines with related and overlapping spectra of activities. The role of these cytokines in chronic myeloid leukemia (CML) has been investigated. A distinctive pattern of cytokine secretion has been found in chronic myeloid leukemia in chronic phase (CML-CP), in blastic crisis (CML-BC) and in normal subjects. Serum IL-6 levels in CML-CP and CML-BC were significantly raised compared with normal controls (p = 0.0026 for CML-CP and p = 0.0011 for CML-BC). IL-6 was significantly elevated in blastic crisis of CML (103.5 +/- 20.77 pg ml-1) compared with CML-CP (37.35 +/- 10.88 pg ml-1; p = 0.014). IL-6 serum levels were found to correlate significantly with peripheral blood monocyte counts and bone marrow blast and basophil counts. We have analysed monocyte/macrophage function with respect to their ability to produce IL-1, IL-6 and TNF-alpha, spontaneously as well as in response to LPS, in comparison with normal controls. A direct correlation of IL-6 levels in unstimulated and stimulated cultures with bone marrow blast and basophil counts has been observed. From these results it is inferred that the monocyte function is impaired in CML patients, and the cytokine secretion is deficient. Our limited data suggest that serum IL-6 levels may play an important role as a prognostic marker for CML.

Although biopsies of Burkitt's tumors contained no detectable complement-fixing (CF) antigen or antigens, tumor cell lines contained CF antigen or antigens related to the presence of a herpes-like virus particle.

Interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), primarily monocyte-derived cytokines, form a group of proinflammatory cytokines with related and overlapping spectra of activities. The role of these cytokines in chronic myeloid leukemia (CML) has been investigated. A distinctive pattern of cytokine secretion has been found in chronic myeloid leukemia in chronic phase (CML-CP), in blastic crisis (CML-BC) and in normal subjects. Serum IL-6 levels in CML-CP and CML-BC were significantly raised compared with normal controls (p=0·0026 for CML-CP and p=0·0011 for CML-BC). IL-6 was significantly elevated in blastic crisis of CML (103·5±20·77 pg ml−1) compared with CML-CP (37·35±10·88 pg ml−1; p=0·014). IL-6 serum levels were found to correlate significantly with peripheral blood monocyte counts and bone marrow blast and basophil counts. We have analysed monocyte/macrophage function with respect to their ability to produce IL-1, IL-6 and TNF-α, spontaneously as well as in response to LPS, in comparison with normal controls. A direct correlation of IL-6 levels in unstimulated and stimulated cultures with bone marrow blast and basophil counts has been observed. From these results it is inferred that the monocyte function is impaired in CML patients, and the cytokine secretion is deficient. Our limited data suggest that serum IL-6 levels may play an important role as a prognostic marker for CML. Copyright © 1998 John Wiley & Sons, Ltd.

Two Burkitt lymphoma (BL)-derived cell lines, characterized by the accumulation of IgM-κ reactive material in their cell membrane, and one BL-line with no such reactivity were studied. Attempts were made to isolate and further characterize the reactive membrane material. Pepain digests of crude membrane preparations from the surface reactive cell lines were capable of blocking the direct membrane fluorescence reaction while the digest obtained from the non-reactive line demonstrated no blocking activity. Gel filtered and papain digested membrane material, from all three cell lines, produced similar elution curves when rechromatographed on a calibrated Sephadex G-150 column. The membrane fluorescence blocking activity of papain digests, derived from cells with μ and κ chain reactivity, appeared to be associated with material of a molecular weight less than 50,000. When this gel filtered material, and the corresponding fraction from the non-reactive cell line, were subjected to polyacrylamide gel electrophoresis a difference in electrophoretic mobility was noted. Electron microscopy revealed small protein fragments, some of linear dimensions compatible with a molecular weight of roughly 50,000 and the majority even smaller in all three preparations. μ and κ chain reactivity was demonstrable by indirect haemagglutination only in papain digested and gel filtered fractions from the two membrane reactive cell lines. Haemagglutation inhibition with Fc μ fragments indicated that these fragments inhibited the anti-IgM reactivity of red cells coated with the proteolytic products of the two membrane reactive cell lines.