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Biomedical subjects

R Foa

Publications and source records attributed to R Foa.

11 recordsLinked to original sources

Unique genotypic features of infant acute lymphoblastic leukaemia at presentation and at relapse.

Acute lymphoblastic leukaemia (ALL) of infants aged less than 1 year represents a group of patients with peculiar biological features, poor response to therapy and unfavourable prognosis. In order better to characterize this type of leukaemia, we have investigated the immunoglobulin (Ig) and T-cell receptor (TCR) genes configuration of 21 infants with ALL, and compared the genotypic features with the phenotypic and karyotypic data, as well as with the clinical outcome. All cases had a pre-B phenotype; 12 (57%) of them were pre-pre-B ALL (CD10-, CD19+). Six of the 16 cases evaluated (38%) displayed chromosomal abnormalities; five had the typical translocation t(4;11)(q21;23). Eleven cases presented with a white blood cell count greater than 100 x 10(9)/l. The clinical course was unfavourable in 14 patients. The genotype of this group of ALL revealed several peculiarities. (1) Of the 21 cases, six (29%) displayed a multiple rearrangement pattern at the IgH locus. (2) In three cases (15%), the light chain genes were rearranged. (3) The TCR beta and gamma genes were rearranged in only one case (one case at the TCR beta and one at the TCR gamma locus). (4) The TCR delta chain was rearranged in eight cases (40%) and rarely deleted; the rearrangements observed were those most frequently observed in B cell-precursor ALL. Two cases were evaluated both at presentation and at relapse. While the immunophenotype had remained unmodified, comparison of Ig heavy chain gene rearrangements revealed clonal variations in both cases. Taken together, these findings further underline the biological peculiarities of infant ALL compared to ALL which occurs in older children and in adults, and stress the need of differentiated and aggressive therapeutic approach for these patients.

Antigens, Neoplasm

Characterization of EBV-positive lymphoblastoid cell lines obtained from HIV seropositive patients with or without lymphomas.

Epstein-Barr-virus- (EBV-) positive lymphoblastoid cell lines (LCLs) spontaneously arising in vitro were obtained from the peripheral blood of six HIV-seropositive patients and from the peripheral blood and the bone marrow of one patient (LAM) with AIDS and lymphoma. The LCLs from HIV-seropositive patients had phenotypic, cytogenetic, and biological characteristics indistinguishable from those of normal LCLs obtained by infecting B cells with EBV in vitro. The LCLs from LAM patient comprised composite cell populations. Cloning analysis and cell fractionation procedures showed that, beside normal EBV-infected cells, these lines contained a malignant subset population characterized by c-myc rearrangement, abnormal karyotype, and a surface phenotype similar to that of Burkitt's lymphoma cells. Analyses of Ig heavy chain and c-myc oncogene loci showed that these malignant cells were the progeny of a single precursor. Nevertheless, these cells had heterogeneous EBV-fused termini, a finding which indicates that EBV infection followed c-myc rearrangement.

Blotting, Southern

Immunoreactive calcitonin in leukaemia.

A radioimmunoassay was used to measure concentrations of immunoreactive human calcitonin (HCT) in plasma and leucocytes from patients with various leukaemic and myeloproliferative disorders. Plasma immunoreactive HCT concentrations were increased in 32 out of 33 patients with chronic granulocytic leukaemia (CGL) and in all eight patients with acute myeloid leukamia (AML) at presentation or in relapse. Out of 11 patients with other myeloproliferative disorders, eight had increased plasma immunoreactive HCT concentrations. Buffy-coat-cell extracts and culture media from peripheral leucocytes of patients with CGL also contained increased immunoreactive HCT concentrations. In contrast, plasma from patients with chronic lymphocytic leukaemia, acute lymphoblastic leukaemia, and AML in remission had low or undetectable immunoreactive HCT concentrations. Increased plasma and cellular concentrations of immunoreactive HCT may be a consequence of abnormal proliferation of myeloid cells and might prove to be valuable in predicting relapse in patients with myeloid leukaemias.

Calcitonin

Alkaline phosphatase in human lymphocyte subpopulations.

The levels of membrane alkaline phosphatase have been measured on different lymphocyte fractions from human peripheral blood separated on bovine serum albumin discontinuous gradients. The peak in enzyme activity was observed in a non-T-, non-B-cell fraction, rich in "null" lymphocytes; the lowest values were found in the fraction with the highest proportion of T-cells.

Alkaline Phosphatase

Clinical staging and immunological findings in chronic lymphocytic leukemia.

Several immunological markers were tested in 52 untreated cases of chronic lymphocyte leukemia (CLL) to see whether their frequency differed according to the clinical stage in Rai's system. The leukemic cells in all cases had B-cell features as shown by monoclonal immunoglobulins on the cell surface (SmIg) and/or a high percentage of mouse RBC (M)-rosettes. Of the two B-cell markers, the M-rosette test was the more consistently positive. The frequency of these markers did not correlate with clinical staging. The percentage of T-lymphocytes, low in all cases, was found to correlate inversely with the lymphocyte counts, which were higher in advanced stages. The absolute number of T-lymphocytes was above normal in most cases, but did not relat to staging. At least one of the serum Ig, most commonly IgA, was decreased in 87% of cases. Low Ig were slightly less common in Stages 0-I than in advanced stages (II-IV). The above features were also examined in two groups of CLL patients: with stable (9) or progressive (16) disease. The only difference observed between the two groups was that surface IgM only was present in 1 of the 9 stable cases as compared to 9 of the 16 progressive ones. Our findings do not support the suggestions that surface IgM is a feature of a benign form of CLL or that the absolute number of T-lymphocytes correlates with prognosis.

Adult

T-lymphocyte colonies in normal blood, bone marrow and lymphoproliferative disorders.

The formation of T-lymphocyte colonies was studied in normal individuals and in different lymphoproliferative disorders, using the double layer technique of Lowenberg & de Zeeuw (1977). All normal peripheral blood and bone marrow samples formed colonies: range 102-270 (mean 177) and 55-245 (mean 138) per 1 X 10(5) cells, respectively. Bone marrows from acute leukaemias in complete remission showed normal or increased colony formation. The T cell nature of the colonies was shown by rosette formation with sheep and human red blood cells (RBC). Most lymphoproliferative disorders of T and B cell either failed to grow colonies or showed reduced colony numbers. This was of particular interest in the chronic T cell disorders in which a high proportion of T cells was plated. This technique may help in the further characterization of leukaemic cell populations and may also provide clues on the distribution of particular subsets of T-lymphocytes in peripheral blood and bone marrow.

Adult

Cell membrane enzymes. II. Alkaline phosphatase and alkaline phosphodiesterase I in normal and leukaemic lymphocytes.

The distribution of two cell membrane enzymes, alkaline phosphatase and alkaline phosphodiesterase I has been studied in normal and leukaemic lymphocytes. No reduction in the level of activity of either enzyme was found in the chronic or acute B- and T-cell leukaemias. Alkaline phosphatase activity was elevated in the lymphocytes from T-CLL, cord blood and tonsils and the blast cells from Null-ALL. Alkaline phosphodiesterase was elevated in lymphocytes from cord blood and tonsils and the blast cells from Null-ALL. As findings in Null-ALL were based on only two cases, they need confirmation in a larger series. The significance of these results is discussed in relation to current theories of maturation and differentiation in the lymphoproliferative disorders.

Alkaline Phosphatase

5' nucleotidase activity in leukaemic lymphocytes.

The enzyme 5' nucleotidase (E.C.3.1.3.5.) is present in lymphocytes isolated from the blood of normal subjects. The activity was extremely low in lymphocytes from 17 patients with B lymphocytic leukaemias. Removal of normal lymphocytes from the B-cell leukaemic samples decreased further the enzyme activity. Moderately low values were observed in three cases of T-ALL and in the cells from a case of Sézary syndrome. In contrast, normal or high values were observed in three cases of ALL in which T and B markers were not demonstrable and in two of T-CLL. No differences were observed in partially purified subpopulations of normal B and T cells.

B-Lymphocytes