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Biomedical subjects

D Catovsky

Publications and source records attributed to D Catovsky.

At least 109 records · Page 6Linked to original sources
PubMed1988

Terminal deoxynucleotidyl transferase positive acute myeloid leukaemia: an association with immature myeloblastic leukaemia.

The morphology, membrane markers and ultrastructural cytochemistry of 39 cases of acute myeloid leukaemia (AML) with variable proportion (10-99%) of terminal deoxynucleotidyl transferase (TdT) positive blasts was compared with that of 134 cases of TdT negative AML. The incidence of TdT positive AML was 22.5% and this was significantly higher in poorly differentiated myeloblastic (M0 and M1) types (54%) than in all other FAB subtypes (10%; P less than 0.001). Our findings suggest heterogeneity among TdT positive cases. Whilst the majority correspond to genuine TdT positive AML in which evidence for exclusive myeloid nature was demonstrated by phenotypic, cytochemical and ultrastructural markers, a distinct minority (22%) of cases had mixtures of lymphoid and myeloid blasts. A change in phenotype occurred in three out of six cases studied in relapse. There was no difference in the incidence of immunoglobulin (Ig) gene rearrangement between TdT positive (two out of 12) and TdT negative (one out of 11) cases, although published data suggests that Ig gene rearrangement is significantly more common in TdT positive cases. The determination of TdT in AML allows the identification of cases of mixed acute leukaemia which probably represent proliferations of multipotent progenitor cells. The majority of TdT positive cases, nevertheless, correspond to immature types of myeloblastic leukaemia which may constitute a clinically distinct subgroup.

Adult↗
PubMed1988

Regression of intracerebral lesions in T prolymphocytic leukaemia treated with intravenous deoxycoformycin.

A case of T-prolymphocytic leukaemia (T-PLL) presenting with deafness and confusion is reported. Computerised tomography (CT) of the head showed several well-defined, rounded, high attenuation areas in the temporal, parietal and occipital regions of the brain substance that were suggestive of metastases. Treatment with weekly intravenous deoxycoformycin produced complete resolution of the CT abnormalities together with haematological evidence of disease regression 6 weeks after treatment was started.

Antineoplastic Agents↗
PubMed1988

Comparison of immunoperoxidase staining with indirect immunofluorescence, ELISA, and Western blotting assays for detecting anti-HTLV-I antibodies in systemic lupus erythematosus.

Serum antibodies against human T cell leukaemia virus type I (HTLV-I) were investigated in 12 patients by four methods: indirect immunoperoxidase staining, indirect immunofluorescence, enzyme linked immunosorbent assay (ELISA), and strip radioimmunoassay based on the Western blotting assay. Seven patients had systemic lupus erythematosus (SLE) and five various autoimmune diseases with one or more circulating autoantibodies. Serum samples from three patients were found to be HTLV-I-positive by the ELISA assay and sera from five patients showed a non-specific reaction by indirect immunofluorescence. These sera were negative when tested by indirect immunoperoxidase staining and Western blotting assay. All four methods gave positive results when tested with samples from 19 HTLV-I carriers and 16 patients with adult T cell leukaemia. Indirect immunoperoxidase staining and Western blotting assay are probably useful and more specific assays for the detection of anti-HTLV-I antibodies in samples from patients with autoimmune diseases.

Adult↗
PubMed1988

Morphology and immunology of circulating cells in leukaemic phase of follicular lymphoma.

Ten patients with follicular lymphoma presented with a high white cell count (45-220 x 10(9)/l) which resembled chronic lymphocytic leukaemia (CCL): all had pronounced splenomegaly and, except one, generalised lymphadenopathy. The blood lymphocytes were small with scanty cytoplasm, densely condensed nuclear chromatin, and deep clefts originating in sharp angles from the nuclear surface. CLL cells are larger, have more cytoplasm, a different pattern of chromatin condensation, and may have shallow nuclear indentations or foldings rather than clefts. The circulating follicular lymphoma cells had moderate to strong membrane immunoglobulins (SmIg), low mouse (M)-rosettes, strong reactivity with the monoclonal antibody FMC7, and occasional expression of the CD5-antigen; at least one third of cells in each case were positive with anti-cALLa (J5,CD10). Half the cases were referred as B-CLL but none had the typical B-CLL immunophenotype: weak SmIg, M-rosettes of greater than 50%, CD5 positive, FMC7 and J5 negative. The diagnosis of follicular lymphoma was confirmed by lymph node biopsy in seven of the 10 cases. The overall response to treatment was poor and five patients died within three years of diagnosis. This aggressive form of follicular lymphoma needs to be distinguished from B-CLL as different management is required.

Adult↗
PubMed1988

Early expression of MCS2 (CD13) in the cytoplasm of blast cells from acute myeloid leukaemia.

The expression of two myeloid antigens identified by the monoclonal antibodies (McAb) MCS2 (CD13) and MY9 (CD33) was investigated in 136 cases of leukaemia. MCS2 was positive in blast cells of 78 of 88 (88.5%) and MY9 in 51 of 81 (64%) cases of acute myeloid leukaemia (AML) and chronic granulocytic leukaemia in myeloid blast crisis. One or other McAb, or both, were positive in all but 2 (2.3%) of these cases. MCS2 was more sensitive than MY9 to detect blasts of the myeloid lineage due to its most frequent reactivity in the cytoplasm of fixed cells by the immunoperoxidase (IP) technique compared with its membrane expression on cell suspensions by immunofluorescence (IF). MY9 was not suitable for tests on fixed cells. MCS2 was positive by IP but not by IF in 24% of AML, but the reverse was not observed. This suggests that the antigen detected by MCS2 is expressed in myeloblasts first in the cytoplasm and later on the cell membrane, pattern which is similar to that of the early antigens CD3 and CD22 in T and B lineage lymphoblasts, respectively. MCS2 was always positive in FAB types of AML-involving myeloblasts (M1-M4), including cases of undifferentiated morphology (M0), whilst MY9 was more frequently positive in monocytic leukaemia (M5). On the other hand, MCS2 was positive in 4 of 33 cases of acute lymphoblastic leukaemia and MY9 in 1. We conclude that both McAb, particularly MCS2, contribute to the better characterisation of myeloid leukaemias but that other tests are required to clarify the nature of the blasts when unexpected reactivities are observed.

Antibodies, Monoclonal↗
PubMed1988

B prolymphocytic leukemia cell lines: phenotype and response to B cell differentiation factor.

Three recently-derived cell lines of prolymphocytic leukemia origin were studied. The phenotype of the cells, analysed in terms of expression of immunoglobulin and other B cell maturation markers, indicates that the cells are mature B lymphocytes close to the plasma cell stage of differentiation. All three cell lines secrete IgM, and two of the three lines respond to B cell differentiation factor with an increased secretion of IgM.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1988

T-cell leukemias with rearrangement of the gamma but not beta T-cell receptor genes.

beta and gamma T cell receptor (TCR) gene configuration was studied in 12 patients with large granular lymphocyte T cell leukemia (LGL-leukemia). Both genes were found rearranged in ten cases. In the remaining two patients TCR beta was found in germline configuration. In one of them rearrangement of T cell-rearranging gene gamma (TRG gamma) and a gamma mRNA were demonstrated. We suggest that in this patient the leukemic T cells arose from one of the rare T cells bearing a gamma-delta rather than an alpha-beta TCR heterodimeric molecule. In the other patient several discrete TRG gamma rearrangements were detected. Because her leukemic cells were shown to be monoclonal on the grounds of their karyotype, we suggest that her leukemia originated before any rearrangement had taken place. The combined use of TCR beta and TRG gamma probes provides new information on the origin and clonal expansion of lymphoid cells in LGL-leukemia.

Antigens, Differentiation↗
PubMed1988

Different expression of CD3 and CD22 in leukemic cells according to whether tested in suspension or fixed on slides.

The expression of antigens detected by monoclonal antibodies of the CD22 and CD3 groups was studied, by immunofluorescence (IF) on cell suspension and by immunoperoxidase (IP) on cells fixed on cytospin slides, in a range of B- and T-cell malignancies. CD22 was demonstrated in the B-cell leukemias more frequently by IP than by IF; in B-lineage acute lymphoblastic leukemia (ALL) it was positive only by IP. In chronic lymphocytic leukemia and lymphoplasmacytic tumors approximately 40% of cases were CD22 positive by IP but few by IF. In other disorders of mature B cells, CD22 was positive by both methods in most cases. CD3 was demonstrated by IP in all 48 cases of T-cell leukemia and lymphoma regardless of the maturation stage (i.e., from early thymic to mature T cells). This was not the case by IF, where only 16% of T-ALL and 73% of cases with postthymic T-cell leukemias were recorded as positive. The greater reactivity of CD3 and CD22 by IP reflect the early cytoplasmic expression of the antigens in immature T and B cells, respectively, as well as the possible greater sensitivity of the IP method. These differences should be taken into account when describing results in lymphoid malignancies. CD3 was not expressed in cells from any of the B-cell leukemias, and likewise, CD22 was not demonstrated in any of the T-cell disorders, confirming that both reagents are highly specific for their respective lineages.

Antibodies, Monoclonal↗
PubMed1988

The UK Medical Research Council CLL trials 1 and 2.

The Medical Research Council (MRC) Working Party on Leukaemia in Adults has conducted two randomised trials in CLL since 1978. CLL 1 ran from 1978 to 1984 and recruited 660 eligible patients. The number of males was twice the number of females and the distribution of cases by stage was different in the sexes: 58% of females were stage A, 25% stage B and 17% stage C; in males the proportions for stages A, B and C were 40%, 30% and 30% respectively. The most important prognostic factor was stage (A, B, C), followed by age, sex and response to treatment, which were confirmed as independent variables by stratified log-rank and Cox multivariate analyses. Causes unrelated to CLL accounted for 28% of all deaths and were more common in older patients and in stage A disease. No significant difference was observed between the CLL 1 treatment schedules: chlorambucil, penta Cop and splenic irradiation (SI), although a somewhat better survival was seen for patients treated by SI. (When CLL deaths only were considered SI appeared superior to chlorambucil (p less than 0.05]. CLL 2 started in 1984 and is still accruing patients; 556 had been entered by July 1988. This trial compares early versus delayed therapy for stage A, chlorambucil with and without prednisolone for stages B and C in patients with a small or nonpalpable spleen, and SI vs chlorambucil with or without prednisolone for stages B and C in patients with a larger spleen (greater than or equal to 5 cm).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1988

The establishment of cell lines from chronic B cell leukaemias: evidence of leukaemic origin by karyotypic abnormalities and Ig gene rearrangement.

We have studied the capacity of peripheral blood cells from 26 chronic B cell leukaemias to proliferate continuously in culture; 72 attempts to establish cell lines were made. The cells were treated in vitro with or without stimulating agents: Epstein-Barr virus (EBV) and/or phorbol-ester (TPA) were the most frequently used. Fourteen cell lines of continuous growth were established from cells from 11 patients, but only four of these were proven to be derived from the original leukaemic cells. Only in the latter four lines were the karyotypic abnormalities and the patterns of immunoglobulin (Ig)-gene rearrangements identical to those found in the patients' leukaemic cells. On the other 10 lines, five had both kappa- and lambda-producing cells, and the remaining five, despite showing light-chain restriction, were proved to be non-leukaemic clones by comparing the Ig-gene rearrangement patterns before and after culture. Three of the four leukaemic cell lines (JVM-2, JVM-3 and JVM-13) were induced by EBV + TPA and derived from prolymphocytic leukaemia (PLL) cases; the fourth (JVM-14) originated from a case of chronic lymphocytic leukaemia (CLL) with increased percentage of prolymphocytes whose cells were stimulated in vitro with EBV. The immunophenotype of the three PLL lines is more mature than that of the original prolymphocytes, as shown by a reduction in surface-Ig and FMC7 expression, enhancement of cytoplasmic-Ig and increase in CD38- and transferrin receptor-positive cells. The cells from line JVM-14 retained the CD5-antigen, a marker of CLL. This study suggests that PLL and some CLL clones are arrested at a stage of maturation ideally suited to be triggered to continuous proliferation in culture. The presence of consistent chromosomal abnormalities in PLL may offer an alternative explanation for the greater proliferative potential of these cells in vitro.

Antigens, Neoplasm↗
PubMed1988

T-cell chronic lymphocytic leukaemia: the spectrum of mature T-cell disorders.

Mature (post-thymic) T-cell malignancies comprise a heterogeneous group of diseases with distinct clinical, morphological and immunophenotypic features. As some of these features overlap in the various disorders, it is essential to use a number of diagnostic criteria to define the clinicopathological entities, namely: membrane markers, morphology by light and electron microscopy, clinical features, seroepidemiology of HTLV-I, histopathology, cytogenetic studies and DNA analysis. The latter, which is necessary to document clonality and confirm T-lineage, examines the rearrangement of the T-cell receptor beta, gamma and delta genes. By means of this multiparameter approach, it is possible to distinguish within the post-thymic leukaemias 4 disease entities: T-chronic lymphocytic leukaemia or large granular lymphocyte leukaemia, T-prolymphocytic leukaemia, adult T-cell leukaemia/lymphoma and Sézary syndrome.

Cell Differentiation↗
PubMed1987

Membrane phenotype and response to deoxycoformycin in mature T cell malignancies.

The adenosine deaminase inhibitor deoxycoformycin was used in low doses to treat 19 patients with clinically aggressive T cell malignancy with a mature membrane phenotype. The patients comprised eight with prolymphocytic leukaemia, two with chronic lymphocytic leukaemia, four with adult T cell leukaemia-lymphoma, three with Sézary syndrome, and two with T cell lymphoma. Two thirds of the patients had been resistant or minimally responsive to combination chemotherapy. Complete remission was obtained in five patients (two with prolymphocytic leukaemia and one each with chronic lymphocytic leukaemia, adult T cell leukaemia-lymphoma, and Sézary syndrome) and partial remission in two others. Unmaintained complete remission lasting more than one year was seen in three patients. Responses were obtained only in patients with CD4+,CD8-membrane markers (seven out of 10), and no responses were recorded in any of the nine patients with a different phenotype. In this series remission appeared to correlate with the membrane phenotype of the neoplastic cell and not with the cytopathological diagnosis. Future studies should establish the biochemical basis for the greater sensitivity of CD4+ lymphoid cells to deoxycoformycin.

Adult↗
PubMed1987

Establishment and characterization of three new malignant lymphoid cell lines.

We have established 3 new EBV-negative cell lines, designated Sc-1, Ri-1 and Ci-1, from patients with B-cell lymphoma/leukemia. We characterized them by cytogenetics and by study of surface membrane antigens with a panel of monoclonal antibodies (MAbs), surface and cytoplasmic immunoglobulin (Ig) expression and Ig heavy- and light-chain genes. All 3 lines had a 14q+ abnormality. Ri-1 also had translocations involving chromosomes 2, 8 and 18. Ci-1 also had abnormalities involving chromosomes 2, 8 and 22 and its karyotype was 46, XX, t(2;8), t(14;22). The t(2;8) had the same breakpoints as those reported in some cases of Burkitt's lymphoma. We also studied a classical Ph1-positive cell line previously established by Pegoraro et al. (1983) and designated BV173. The phenotypes of these 4 lines based on Ig expression and marker studies correlated well with their respective genotypes. Our results are in keeping with the notion that leukaemic cell populations are clonal expansions of cells "frozen" at a particular stage in their differentiation. Specifically, BV173 cells are at an early stage of B-cell differentiation, Ri-1 and Ci-1 cells are at intermediate stages and Sc-1 cells are at a relatively late stage in the B-cell lineage.

Adult↗
PubMed1987

Biochemical mechanisms of deoxycoformycin toxicity in chronic leukemias.

The in-vitro effects of deoxycoformycin (dCF) on dATP, NAD, ATP and DNA strand breaks have been evaluated in the cells from 42 patients with various types of chronic lymphoid leukemia. These included 18 with B-cell chronic lymphoid leukemias of different types (BCL); 10 with hairy cell leukemia (HCL) and 14 with T-cell chronic lymphoid leukemias of different types (TCL). The dATP concentrations in HCL, BCL and TCL increased from means of 2.9, 1.8 and 3.0 to 100.3, 68.2 and 51.3 pmol/10(6) cells respectively after 2 h with 10(-5) M dCF and 10(-4)M deoxyadenosine. After 18-24 h, the NAD levels and total double-stranded DNA decreased to 37 and 12.5% (HCL) to 36 and 21.6% (BCL) and 40 and 20.5% (TCL) of control values respectively. Similar decreases were observed in ATP levels. The results do not suggest that these measurements in vitro would predict which patients with these disorders will respond to dCF therapy. Although HCL responds particularly well to dCF in vivo, no difference in the in-vitro effects of dCF studied here could be detected between cases of HCL and the other types of chronic leukemia.

Adenosine Triphosphate↗
PubMed1987

Clinical and laboratory features of de novo acute myeloid leukaemia with trilineage myelodysplasia.

Primary myelodysplastic syndromes progress to acute myeloid leukaemia (AML) in about 30% of cases. We have sought evidence of pre-existing trilineage myelodysplasia (TMDS) using the FAB criteria (1982) in 160 consecutive cases of primary de novo AML. TMDS was found in 24 cases (15%) including two of 33 cases of M1 (6%), four of 40 cases of M2 (10%), none of 18 cases of M3, five of 31 cases of M4 (15%), six of 30 cases of M5 (20%), all of six cases of M6 and one of two cases of M7. The median presentation bone-marrow blast-cell count in the 24 AML/TMDS cases was 53% (30-90%) and 82% (45-100%) in the 136 cases of AML without TMDS. 60% of the AML/TMDS bone-marrow aspirates contained fewer than 60% of blasts compared with only 11% of those from AML without TMDS (P less than 0.001). In AML the occurrence of symptomatic cytopenias when the marrow blast-cell count is below 60% and the peripheral blood blast-cell count is below 20% is highly correlated with dysplastic haemopoiesis (P less than 0.001).

Adolescent↗