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S L Melvin

Publications and source records attributed to S L Melvin.

28 records · Page 2Linked to original sources

Aneuploidy and percentage of S-phase cells determined by flow cytometry correlate with cell phenotype in childhood acute leukemia.

Cellular DNA content distributions of propidium-iodide-stained bone marrow blasts were determined by flow cytometry (FCM) for 225 untreated children with acute leukemia and were correlated with leukemia cell phenotype and karyotype. Aneuploidy of the primary malignant stem line was detected in 54 cases (24%): 51 hyperdiploid and 3 hypodiploid. A second stem line with approximately twice the DNA content of the primary stem line was recognized by FCM in 28 cases (23 ALL, 5 ANLL) and may be an important source of leukemia cell heterogeneity. The degree of DNA content abnormality detected by FCM was highly correlated (r = 0.98) with the number of whole chromosome gains or losses in the leukemia karyotype. Aneuploidy detectable by FCM was more frequent in acute lymphoblastic leukemia (ALL) (52 of 173, 30.1%) than in acute nonlymphoblastic leukemia (2 of 52, 3.8%) (p less than 0.001). In the ALL group, aneuploidy was significantly correlated with the cell surface expression of common ALL antigen: 46 of 127 antigen-positive cases were aneuploid compared to 6 of 46 antigen-negative cases (p less than 0.003). Only 2 of 21 cases of T-cell ALL without common ALL antigen had detectable aneuploidy, which was significantly less than in the common ALL group (p = 0.02). The median percentage of cells in S-phase was significantly greater for B-cell and erythrocyte rosette-positive T-cell ALL, than for the other phenotypic subgroups. We conclude that aneuploidy and S-phase cell percentage are correlated with the state of leukemia cell differentiation. The biologic basis for the correlation is not established, but may be linked to the process of malignant transformation.

Acute Disease↗

Immunological definition of leukemic cell surface phenotypes.

Immunological phenotyping of blasts from over 200 children with acute lymphocytic leukemia (ALL) reveals both interpatient differences and phenotypic heterogeneity in the blast population from individual patients. A battery of five independent lymphocyte differentiation markers, erythrocyte-forming rosettes. T-cell antigens, Ia-like antigens, the common ALL antigen, and surface immunoglobulin, permit classification of all ALL specimens into four major marker groups. These are common, T-cell, B-cell, and undifferentiated ALL. Heterogeneity in the marker phenotypes within each of the major groups is observed. Within individual erythrocyte receptor-positive ALL specimens, phenotypic heterogeneity in the blast population is demonstrated. Sequential determinations of the blast phenotype during periods of active disease reveal a second example of intrapatient blast cell heterogeneity. Differences in phenotype of the dominant blast populations present prior to treatment and at relapse are observed in sequential studies of individual patients. These shifts in phenotype are nonrandom. They result most frequently from losses in single differentiation markers. A unifying hypothesis which explains these observations of phenotypic heterogeneity is that ALL blasts manifest limited lymphoid-like differentiation.

Antigens, Neoplasm↗

A clinical perspective on cell markers in acute lymphocytic leukemia.

Two hundred consecutive new patients, with acute lymphocytic leukemia (ALL) have been studied with a battery of five cell marker assays to determine if a classification system with prognostic significance can be developed; 182 have been classified among four groups as follows: 33 T-cell, 3 B-cell, 126 common, and 20 undifferentiated ALLs. Patients with T-cell disease are likely to have unfavorable clinical prognostic features and a poor response to therapy. Rare patients with B-cell disease are closely related clinically to non-Hodgkin's lymphoma. Those with common ALL infrequently have unfavorable clinical features and have a superior outcome to that of T-cell patients. Children with undifferentiated markers seem to respond less well to treatment than do those with common ALL, yet may not be identifiable as poor risk by clinical features. What remains to be resolved with further observation is whether these marker patterns are more reliable indicators of prognosis than the usual clinical determinants predisposing to treatment failure (high white blood cell count, mediastinal mass, and central nervous system disease). At the present time, it appears that in the absence of poor-risk clinical prognostic features, patients with common ALL are more likely to have lasting remissions than those with erythrocyte-rosette-positive T-cell disease or those with ALL that is undifferentiated by markers.

Antigens, Neoplasm↗

Clinical utility of initial terminal deoxynucleotidyl transferase determinations in childhood acute leukemias.

Terminal deoxynucleotidyl transferase (TDT) activity was measured in bone marrow lymphoblasts obtained at diagnosis from 168 consecutive patients with childhood acute leukemia. Absolute concentrations of TDT were increased (greater than or equal to 20 units/10(8) blasts) in samples from 98 of 112 assessable patients with acute lymphocyte leukemia (ALL). The values ranged from less than 1 to 1502 units/10(8) blasts with a median of 90 units contrasted with less than 1 to 219 units (median, 2.6 units) in studies of children without leukemia. Results of an immunofluorescence assay were in good agreement with enzymatic detection of the polymerase. Among 115 patients with adequate marrow smears, 105 had TDT-positive blasts. By contrast, in most children with acute myelogenous leukemia, TDT activity was either undetectable or less than 10 units/10(8) blasts. Although the highest levels of TDT were found in blasts with the common ALL phenotype, quantitative determinations were not significantly related to the major immunological subtypes of ALL or to morphological features or periodic acid-Schiff reactivity of the lymphoblasts. The probability that a newly diagnosed case of leukemia would be ALL was 90% if TDT levels were greater than 20 units/10(8) blasts. We conclude that absolute concentrations of TDT, as determined in this study, are of little value in identifying subclasses of ALL. The immunofluorescence assay, which is much less expensive and easier to perform than the enzyme assay, should prove useful for confirming the diagnosis of ALL and for detecting extramedullary sites of leukemic infiltration.

Acute Disease↗

Identification of a leukemia-associated antigen of human acute lymphocytic leukemia.

A human leukemia-associated antigen (LAA) has been identified by immunofluorescence and electrophoretic analyses. LAA was detected on the surfaces of cells from patients with acute lymphocytic leukemia (ALL) as well as on the surfaces of leukemia cells from the established cell lines NALM-1, NALM-16, MOLT-4, CCRF-CEM, and RPMI 8402. The antigen was not detected on BALM-1 or Raji cells (established B-cell lines), bone marrow cells from ALL patients in remission, or on blood lymphocytes from normal donors. This antigen was most frequently associated with common ALL (cALL); however, cells from 2 of 12 patients with T-cell ALL and 1 patient with B-cell ALL also expressed this antigen. Under reduced conditions, the antigen had an approximate molecular mass of 100,000 daltons as determined by sodium dodecyl sulfate--polyacrylamide gel electrophoresis and autoradiographic analysis and appeared to be the same cALL antigen that has recently been described by others. The probability that LAA is a normal differentiation antigen was discussed.

Antibody Specificity↗

Histoplasmosis mimicking childhood non-Hodgkin lymphoma.

Cell surface markers are becoming increasingly important in the diagnosis of malignant lymphoid diseases. We present a case of pulmonary histoplasmosis with a pleural effusion. The differential diagnosis included non-Hodgkin lymphoma because the pleural fluid cells were cytologically identical to convoluted lymphoblasts; the cells also formed rosettes with sheep erythrocytes at 37 degrees C, suggesting that they were malignant thymus-derived lymphoblasts. Since cultures of pleural fluid were negative for bacteria and fungi, the correct diagnosis of histoplasmosis was made only after conventional histology identified Histoplasma capsulatum organisms in pleural nodules. Thus, until we have a better understanding of the significance of cell surface markers, we should continue to rely on conventional histology for the diagnosis of lymphomas.

Child↗

Comparison of techniques for detecting T-cell acute lymphocytic leukemia.

Three versions of the E-rosette test, one using untreated sheep erythrocytes at 37 degrees C, another using such cells at 4 degrees C, and a third using sheep erythrocytes treated with S-(2-aminoethyl)isothiouronium bromide hydrobromide (AET), were applied to each of 72 bone marrow specimens from as many unselected patients with untreated acute lymphocytic leukemia (ALL). The same specimens were also examined for T-cell antigens, based on reactivity with an antithymocyte serum. Lymphoblasts in eight ALL specimens formed E rosettes at 37 degrees C; no other E-positive specimens were identified when the assay was done at 4 degrees C. With AET-treated erythrocytes, lymphoblasts from these eight specimens and six additional specimens readily formed rosettes. T-cell antigens were detectable in all specimens positive for rosette formation withe untreated erythrocytes, in four of the six specimens positive for rosette formation with AET-treated erythrocytes, and in four specimens that showed no rosette formation under any of the experimental conditions used. Altogether, 18 specimens contained lymphoblasts with one or more surface markers characteristic of T-cell leukemia. These findings indicate that more specimens are likely to be identified at T-cell luekemias when E-rosette tests of increasing sensitivity and assayss for T-cell antigens are used. Some leukemic blasts do not possess the full array of membrane receptors and antigens usually associated with T cells. A combination of E-rosette tests and serologic tests is necessary to determine reliably the relationship of the test specimen to either T-cell ALL or common ALL and to establish the clinical significance of blasts that express membrane properties intermediate between those of T-cell ALL and common ALL.

Antilymphocyte Serum↗