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M Valtieri

Publications and source records attributed to M Valtieri.

62 records · Page 4Linked to original sources

Growth factor requirements of childhood acute leukemia: establishment of GM-CSF-dependent cell lines.

Eight permanent cell lines were established from cells of 50 consecutive patients with childhood acute leukemia. Three cell lines required growth factor-containing conditioned media. Analysis using blocking antisera and recombinant granulocytic macrophage (GM) colony-stimulating factor (CSF) identified GM-CSF as a growth factor required to establish the latter three cell lines and necessary for their continuous proliferation in chemically defined medium. Two of the GM-CSF-dependent cell lines were derived from patients with undifferentiated T- and a biphenotypic B-myelomonocytic leukemia, which suggests that GM-CSF might maintain proliferation of leukemias originating from immature progenitor cells. Cytogenetic analysis indicated that all established leukemic cell lines were aneuploid, with six lines containing chromosomal alterations related to those observed in the leukemic cells of the patient. Two patients did not have an abnormal clone identified in the marrow but did yield an aneuploid cell line. These studies indicate that GM-CSF-dependent leukemic cell lines can be established in a fraction of childhood leukemia. These cell lines lend themselves to studies aimed at the evaluation in vitro of the role of growth factors in controlling proliferation and differentiation of leukemic cells.

Acute Disease↗

Heterogeneity of chromosome 22 breakpoint in Philadelphia-positive (Ph+) acute lymphocytic leukemia.

In chronic myelogenous leukemias (CML) with the t(9;22)(q34;q11) chromosome translocation the breakpoints on chromosome 22 occur within a 5.8-kilobase segment of DNA referred to as "breakpoint cluster region" (bcr). The same cytogenetically indistinguishable translocation occurs in approximately 10% of patients with acute lymphocytic leukemias (ALL). In this study we have investigated the chromosome breakpoints in several cases of ALL carrying the t(9;22) translocation. In three of five cases of ALL we found that the bcr region was not involved in the chromosome rearrangement and that the 22q11 chromosome breakpoints were proximal (5') to the bcr region at band 22q11. In addition, we observed normal size bcr and c-abl transcripts in an ALL cell line carrying the t(9;22) translocation. We conclude, therefore, that if c-abl is inappropriately expressed in ALL cells without bcr rearrangements, the genetic mechanism of activation must be different from that reported for CML.

Adolescent↗

Peripheral T cell lymphoma in adults: morphological and phenotypical study of four cases.

In the present study we investigated the lymph node morphology and distribution of cell surface phenotypes in four cases of adult peripheral T cell lymphoma. Histologically, the tumors were classified as T zone lymphoma, T cell lymphoma with large multilobated nuclei and T cell immunoblastic sarcoma. In the T zone lymphoma the neoplastic lymphocytes were E+ (90%) and exhibited intensive focal staining for acid phosphatase (93%) and acid esterase (92%); the phenotype distribution revealed low expression of the T-3 antigen (49%), selective expression of the T-4 antigen (72%) and poor expression of T-6 (10%) and T-10 antigens (22%). Some of these features are present in normal and in neoplastic immature T cells. In the remaining three cases the majority of lymph node cells were E+ (59-75%), T-3+ (67-80%) and T-8+ (43-55%). A distinctive feature of the T cell immunoblastic sarcoma was the presence of high percentages of DR+ cells (62%; 63%). Thus our results indicate that the morphological heterogeneity of peripheral T cell lymphoma is also paralleled by a variety of surface phenotypes and that phenotype studies may provide a useful contribution to identification and accurate classification of peripheral T cell neoplasms.

Adult↗

T-lymphocyte subsets in human lymph nodes: relative increase of OKT-8+ cells in neoplastic and reactive B-cell proliferation.

Cell suspensions obtained from 54 human lymph nodes involved by different pathological conditions were characterized by conventional markers and by the OKT-3, OKT-4, OKT-8, OKIa-1, and OKM-1 monoclonal antibodies. In 18 cases of reactive lymphoid hyperplasia, the majority of lymph node cells were mature T lymphocytes (E-RFC = 56 +/- 9%; OKT-3+ = 63 +/- 10%); among T-cell subsets, OKT-4+ cells were 49 +/- 8% whereas OKT-8+ cells were 21 +/- 8% (T4/T8 = 2.7 +/- 1.1). This distribution of T-cell phenotypes was not similar in the different histological types of reactive lymphoid hyperplasia. In fact, an increase in the percentage of OKT-8+ cells (25 +/- 9%; P less than 0.05) and a decrease in the values of the T4/T8 ratio (2.1 +/- 1.0; P less than 0.05) were observed in 9 cases of reactive lymphoid hyperplasia of follicular type when they were compared to the mixed and sinus types. In 13 lymph nodes involved by B-cell lymphoma, the percentage of T lymphocytes was markedly reduced (E-RFC = 21 +/- 12%; OKT-3+ = 27 +/- 18%) and the percentage of OKIa-1+ cells (51 +/- 15%) was significantly (P less than 0.01) increased as compared to reactive nodes; in addition, in these cell suspensions, an increase in the relative proportion of OKT-8+ cells (T4/T8 = 1.4 +/- 0.7; P less than 0.01) could also be demonstrated. Finally, a clear prevalence of OKT-4+ cells on OKT-8+ cells was demonstrated in 5 cases of tuberculous lymphadenitis (T4/T8 = 3.9 +/- 1.5; NS) and in 18 cases of Hodgkin's disease (T4/T8 = 4.2 +/- 2.0; P less than 0.01). In tuberculous lymphadenitis, a significant increase (P less than 0.01) in the percentage of OKM-1+ cells could also be demonstrated.

Antibodies, Monoclonal↗

Hairy cell leukemia: absence of natural killer activity and of interleukin 1 release in OKM-1+ spleen hairy cells.

Phenotypic characterization by monoclonal antibodies of spleen cells obtained from three spleens involved by hairy cell leukemia (about 90% of cells with intracytoplasmic tartrate-resistant acid phosphatase) indicated that the hairy cells are OKT-3-, OKM-1+, and OKIa1+. Neoplastic cells obtained from two lymph nodes involved by B-cell lymphoma were found to be OKT-3-, OKM-1-, and OKIa1+. Functional characterization of the hairy cells present in the spleen indicated that they lack NK activity and do not release Interleukin 1. In fact, spleen hairy cells were not lytic against K-562 tumor cells in a short-term 51Cr-release assay and did not release Interleukin 1 in culture supernatants even after LPS stimulation. In normal individuals, both these cell functions are expressed by subpopulations of OKM-1+ cells.

Adult↗

The human thymus in ageing: histologic involution paralleled by increased mitogen response and by enrichment of OKT3+ lymphocytes.

In the present study, based on 24 individuals aged 5-61 years, the histological pattern of the thymus has been determined and correlated to the thymus lymphocyte in-vitro responses to phytohaemagglutinin (PHA) and concanavalin A (Con A). It has been found that lymphocytes from histologically involuted thymus were significantly more responsive to PHA and Con A stimulation than lymphocytes from histologically normal thymus. These data indicate that thymus age-dependent involution is associated with increased lymphocyte in-vitro reactivity. In addition, in 10 cases the relative proportions of the thymus lymphocyte subpopulations have been determined by the use of monoclonal antibodies OKT3, OKT4, OKT6 and OKT8. These results have been correlated to the histology of the organ and to the mitogen responsiveness of thymus lymphocytes. In normal thymus the majority of the cells were OKT6+, while there were lower numbers were OKT3+. However, in involuted thymus, OKT3+ lymphocytes prevailed over OKT6+ cells. Furthermore, a direct relationship between the proportion of OKT3+ lymphocytes and the response to mitogens has been observed. These findings indicate that the increased mitogen response noticed in histologically involuted thymus is accompanied by an OKT3+-cell enrichment which is paralleled by a depletion of OKT6+ cells.

Adolescent↗

Increased monocyte phagocytosis and decreased lymphocyte mitogen reactivity in colorectal cancer patients.

In the present study we have evaluated monocyte phagocytosis and T lymphocyte in vitro reactivity to mitogens in peripheral blood samples from 14 colorectal cancer patients, from 21 nonneoplastic control patients, and from 22 normal donors. Monocyte and lymphocyte functions were tested before and 1 and 6 months after surgery. Our results indicate the existence of increased monocyte phagocytosis and decreased mitogen reactivity in untreated patients with advanced tumors. These abnormal responses persisted and were even more pronounced after surgery and chemotherapy.

Adenocarcinoma↗