Null Cell Type Research Articles

Chromosome abnormalities in Japanese Burkitt lymphoma cell lines.

Six established Japanese Burkitt lymphoma (BL) cell lines including one case with null cell type were studied by chromosomal banding techniques. The modal chromosome number was diploid or nearly diploid in five cases and hyperdiploid in one case. The marker chromosome 14q+ was observed in four of the six cases; the origin of the extra band was a chromosome 8 in three including the null cell case but could not be identified in the other. The two cases lacking the 14q+ marker had variant translocations involving the long arm of chromosome 8, one of which carried a translocation, t(8;22) (q24;q13) and the other a translocation, t(2;8) (p12;q24). Although structural and/or numerical aberrations were found in all six cell lines, chromosome 8 was the one most consistently involved. This frequent involvement of chromosome 8 in aberrations; therefore, may be an important event in the development of BL rather than the presence of a 14q+ marker chromosome.

886 PERINATAL LEUKAEMIA

Perinatal leukaemia is a rare disorder and extensive cytochemical, morphological and immunological studies have not been carried out in most of the earlier cases. We report four cases of perinatal leukaemia with clinical, morphological, cytochemical, immunological and cytogenetic correlations. Two had acute lymphoblastic leukaemia (ALL) and the other two had acute myeloblastic leukaemia (AML). The age at diagnosis was 5 hours, 9, 34 and 64 days. Initial hemoglobin values ranged from 5.5 gm/dl to 14 gm/dl. WBC counts varied from 60,000/mm3 to 666,000/mm3. In the two with ALL the lymphoblasts were B antigen positive null cell type (Blood 49:371, 1977). Three had normal karyotypes in the marrow cells before treatment. In the fourth a 46XX, 18 P-karyotype was noted with the father showing 46XY t (18p; 10p). Three patients died at 5, 47 and 223 days after diagnosis. One, who had AML, and who is the male member of a dizygotic pair of twins, is alive and disease free 14 years after diagnosis. Our observations indicate that the reported higher incidence of AML in neonates should be more carefully verified. Similar to ALL in somewhat older age groups of children, null cell B antigen +ve ALL appears to be the common phenotypic expression of ALL in neonates. Exchange transfusion was found to be useful in reducing the immediate risk of metabolic and leukostatic complications. In addition, the disease free survivor indicates that long term remission is possible in perinatal leukaemia.

Prolymphocytic Leukemia

A 69-year-old woman previously diagnosed as having chronic lymphocytic leukemia had a lymphocyte count of 1,500 X 10(9)/L develop. Bone marrow and peripheral blood lymphocyte morphology and lymphocyte surface markers were consistent with the diagnosis of prolymphocytic leukemia of the null cell type. The leukemia was resistant to management with alkylating agents, combination chemotherapy including doxorubicin hydrochloride, or leukapheresis. The addition of asparaginase to the previously ineffective prednisone and vincristine sulfate therapy produced a dramatic response during a two-week period with a decrease in the peripheral lymphocyte count from 980 X 10(9) to 20 X 10(9)/L and a return toward normal of the concentration of polymorphonuclear leukocytes. Previously, there has been only infrequent or transient benefit from treatment provided these patients from regimens including chemotherapy, splenectomy, irradiation, and leukopheresis. It is suggested that asparaginase be considered as initial induction therapy for this disease process.

Shifts in Expression of Cell Membrane Phenotypes in Childhood Lymphoid Malignancies at Relapse

AbstractTo determine if cell membrane phenotypes change under the selective pressures of therapy we have conducted a prospective study of 54 children with lymphoid malignancies of T-like, B-like, common, and null cell types. Membrane phenotypes were determined at diagnosis in all patients and again 1-24 mo later in 18 children who either failed induction therapy or had one or more relapses. In 7 patients the cells tested were from relapse sites different than those of the original diagnoses. The data indicate that at relapse most children with lymphoid neoplasias had the same cell membrane phenotype as established at diagnosis, and suggest that the site of relapse did not affect the expression of cell surface markers. However, there were three exceptions: (1) a child initially diagnosed as having null cell acute lymphocytic leukemia had 90% T-antigen-positive blasts in her second-relapse bone marrow; (2) only membrane IgM was present on relapse blasts from a B-cell lymphoma that had both membrane IgM and IgD before initiation of treatment; (3) at diagnosis, bone marrow blasts from a child with T-like leukemia expressed both T antigen and E receptors, but at relapse, bone marrow and pleural fluid cells expressed only T antigens. We postulate that these phenotype shifts may be due to selective effects of therapy on cells at different stages of differentiation.

Shifts in expression of cell membrane phenotypes in childhood lymphoid malignancies at relapse

To determine if cell membrane phenotypes change under the selective pressures of therapy we have conducted a prospective study of 54 children with lymphoid malignancies of T-like, B-like, common, and null cell types. Membrane phenotypes were determined at diagnosis in all patients and again 1-24 mo later in 18 children who either failed induction therapy or had one or more relapses. In 7 patients the cells tested were from relapse sites different than those of the original diagnoses. The data indicate that at relapse most children with lymphoid neoplasias had the same cell membrane phenotype as established at diagnosis, and suggest that the site of relapse did not affect the expression of cell surface markers. However, there were three exceptions: (1) a child initially diagnosed as having null cell acute lymphocytic leukemia had 90% T-antigen-positive blasts in her second-relapse bone marrow; (2) only membrane IgM was present on relapse blasts from a B-cell lymphoma that had both membrane IgM and IgD before initiation of treatment; (3) at diagnosis, bone marrow blasts from a child with T-like leukemia expressed both T antigen and E receptors, but at relapse, bone marrow and pleural fluid cells expressed only T antigens. We postulate that these phenotype shifts may be due to selective effects of therapy on cells at different stages of differentiattion.

Chronic Myelocytic Leukemia Terminating in Blast Cell Crisis with Lymphoblastic Characteristics

A child with chronic myelocytic leukemia (CML), Philadelphia chromosome positive, developed a non-T cell, non-B cell, acute lymphocytic leukemia (ALL) during her blast cell crisis. The diagnosis was suggested by light microscopy and supported by histochemical stains and transmission electron microscopy. Immunologic studies showed the presence of a non-T, non-B leukemic blast population--indistinguishable from the most common form of ALL (null cell type). Markedly elevated terminal deoxynucleotidyl transferase (TdT) activity was found. The findings support the hypothesis that the primary cell involved in CML is a stem cell with pluripotential characteristics; frequently the blast cell proliferative phase terminates in acute myeloblastic leukemia, but it may also terminate in ALL. The TdT activity may be evidence of leukemic transformation and not necessarily related to the thymic origin of the lymphocytes.

Biology of the human malignant lymphomas. IV. Functional characterization of ten diffuse histiocytic lymphoma cell lines

Ten consecutive diffuse histiocytic lymphoma (DHL) cell lines established in our laboratory were studied for the presence of Epstein-Barr virus (EBV) genomes, lysozyme, nonspecific esterase and other cytochemical reactions, phagocytic activity, cytoplasmic immunoglobulin light and heavy chains, and surface receptors to sheep erythrocytes, complement, and the Fc fragment of immunoglobulin. In agreement with previous studies performed on biopsy specimens, our results indicate that the diffuse histiocytic lymphomas, as a histopathologic entity, represent a heterogeneous group of neoplasms, the majority of which are B-lymphocyte in origin. The cell lines appear to fall into three categories based on the following criteria: 1) presence of monoclonal cytoplasmic immunoglobulins (B-lymphocytic type, 6/10 cell lines); 2) presence of non-specific esterase, phagocytic activity, and/or lysozyme (histiocytic type, 2/10 cell lines); and 3) absence of all lymphoid and histiocytic cell characteristics (null cell type, 2/10 cell lines). Despite the fact that many of the lymphoma patients had positive serologies to EBV antigens, all of the DHL cell lines were negative for the presence of EBV genomes. Both of the two B-lymphocytic type and one of the two histiocytic type lines tested were susceptible to infection with EBV, as indicated by synthesis of early antigen and also, in a small proportion of the infected cells, of viral capsid antigen. These prototypic DHL cell lines may permit the development of new criteria for the differential diagnosis and treatment of this highly malignant and diverse group of lymphomas.

MEMREANE MARKERS IN ALL: A STUDY OFF 21 CASES

Twenty one cases of ALL (13 males, 8 females) were analysed for the presence of T and B membrane markers in blood or bone marrow prior to treatment. Their ages were between 2 and 16 years. E rosettes with SRECs(at 48 and 37° C) and with autologous RBCs, HEA and HEAC rosettes were performed. The surface imnunoglobulins(with monospecific antisera to μ, γ and α chains) were detected by using a direct immunofluorescence technique. Seven(33%) were T cell;l (4%) was B cell; and 13(62%) were considered to be null cell type. The male:female ratio was 5:8 in null cell; 7:0 in T cell type. Two cases of T cell type had mediastinal lymphadenopathy. There was no significant difference for the WBC counts between the T and null cell groups. During the first 6 weeks of treatment, 50% of the patients with T cell type and 10% of the patiants with null cell type did not go into remission with classical induction therapy. Forty-two percent of bhe patients with T cell type and 7% of the patients with null cell type had CMS infiltration. Forty-two percent of the patients with T cell type and 12% of the patients with null cell type lied during the observation period of this study.

Cytological Findings and Mitotic Index of Non-Hodgkin's Malignant Lymphoma

Twenty-three cases of non-Hodgkin's malignant lymphoma were studied with referrence to Lukes and Collinsclassification. These cytological pictures were investigated in detail by using a touch smear method. The densityof nuclear pore in some cases was measured with freezefracture method and the relationship between mitotic indexand nuclear pore density was studied and discussed.Surface marker analysis of our cases showed that mostcases of these lymphoma were B cell type. Some of thecases were T cell or Null cell type lymphoma and one casewas a mixture of T cell and B cell types Follicular centercell origin (FCC) was found in 74% of the total cases andthey had B cell surface marker in all cases examined.Most of them were large transformed type lymphoma. Allcases of convoluted type were T cell nature. Undefinedtypes decided in this series showed high degree of variationmorphologically and most of them were Null cell type.There were no difference of mitotic index in nodular typeand the control cases. The mitotic index of the lymphomaof follicular center cell origin among diffuse type showed anincreasing number in this order, small cleaved, largecleaved, small transformed, large transformed, and immunoblastic sarcoma.Our study using a freeze-fracture method showed goodcorrelationship between the density of nuclear pore andmitotic indices.

Immunofluorescent Method for Positive Identification of Null-Cell Type Acute Lymphocytic Leukemias: Use of Heterologous Antiserum

AbstractAcute lymphoblastic leukemia (ALL) patients could be subclassified into two groups depending on whether or not their leukemia cells expressed a B-lymphocyte antigen. The antigen was detected by an indirect immunofluorescence test using rabbit antisera. In the positive group, consisting of 26 of 32 patients, the leukemia cells were of the “null”-cell type, i.e., they did not appear to express currently recognized T- and B-cell markers. Absorption studies indicated that the positive null-cell group expressed a common antigen which was not expressed on the negative group. Of the 6 negative cases, 5 expressed complement receptors and 3 expressed T-cell markers. The negative group was also characterized by high white cell counts and the presence of a mediastinal mass.

Immunofluorescent method for positive identification of null-cell type acute lymphocytic leukemias: use of heterologous antiserum

Acute lymphoblastic leukemia (ALL) patients could be subclassified into two groups depending on whether or not their leukemia cells expressed a B-lymphocyte antigen. The antigen was detected by an indirect immunofluorescence test using rabbit antisera. In the positive group, consisting of 26 of 32 patients, the leukemia cells were of the “null”- cell type, i.e., they did not appear to express currently recognized T- and -b-cell markers. Absroption studies indicated that the positive null-cell group expressed a common antigen which was not expressed on the negative group. Of the 6 negative cases,, 5 expressed complement receptors and 3 expressed T-cell markers. The negative group was also characterized by high white cell counts and the pressence of a mediastinal mass.

IMMUNOHISTOLOGICAL STUDY OF MALIGNANT LYMPHOMA IN HEAD AND NECK

Enzyme cytochemistry, special histlogical staining and surface marker were investigated in 20 cases of untreated non-Hodgkin's lymphoma (17 Reticulum cell sarcomas and 3 lymphosarcamas).Histiocytes exhibit a relatively strong and and thus enzyme cytochemical activity of nonspecific esterase. Non-specific esterase activities were hardly observed in tumor cells. The tumor cells were arisen originally from lymphocytes. Immunoglobulin was identified on the surface of neoplastic lymphocytes in 11 of 20 patients. IgG heavy chain was observed in 5 cases, IgA was in 2 cases. IgG and A was in one, and IgM and G was in one case. Two B cell species could be recognized by cell surface marker study. One had C3 receptor and the other had not.E-rosette formation was oberved in neoplastic lymphocytes in 3 cases. In one case the lymphocytes were identified as B cells. The other two were identified as T cells.However, neoplastic lymphocytes of 7 cases were termed as Null cells since they showed neither of T or B cell markers.The Null cell type of neoplastic lymphocytes was thought to have two origins, one was arisen originally from the Null and the other was from T or B cells whose surface marker was lost.

Poor prognosis of children with acute lymphocytic leukemia and increased B cell markers

IN THE TREATMENT of childhood acute lymphocytic leukemia, the search continues for clinical and laboratory indicators to better predict good and poor prognosis. Age at diagnosis and initial leukocyte count have been shown to be valuable front end prognostic indicators. ~ Since greater than 50% of patients now remain in complete continuous remission longer than five years, attention must be focused on the poor responders? By examining surface markers on lymphoblasts, leukemias can be classified as T cell, B cell, or null cell types. Using this technique, we observed that the bone marrows from three of 37 children with ALL had markedly increased B cell markers. They presented with contrasting clinical and laboratory features but had very poor responses to treatment when compared to the non-B cell patients of similar age and initial leukocyte counts.