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G Cattoretti

Publications and source records attributed to G Cattoretti.

At least 91 records · Page 5Linked to original sources

Molecular and immunological evidence of B-cell commitment in "null" acute lymphoblastic leukaemia.

The DNA configuration of the immunoglobulin (Ig) heavy and light chain genes and the expression of B-cell-related markers were evaluated in 13 cases of non-T, non-B, non-common ("null") acute lymphoblastic leukaemia (ALL). A rearrangement of the Ig heavy-chain gene was found in all cases studied; in 5 of these a structural reorganization of the kappa or lambda light chain gene was also demonstrated. Leukaemic cells from 10 of the 13 cases analysed showed one or more B-cell antigens, the expression of which followed a sequential order of presentation (OKB2, B4, BA-1, B1). The B-cell commitment was confirmed by means of a sensitive immunoperoxidase assay which revealed a weak expression of the common ALL (cALL) antigen in 7/10 cases tested, which were all cALL-negative by conventional immunofluorescence techniques. These findings suggest that in "null" ALL the neoplastic cells show molecular and immunological evidence of B-cell differentiation and that most cases may indeed be characterized by "early" cALL with a very low density expression of the cALL antigen. This was further documented in one case in which the expression of the cALL antigen (and of other B-cell markers) could be induced after exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA). The presence in a few cases of myeloid features, particularly when the cALL antigen could not be demonstrated by the immunoperoxidase assay, suggests that the leukaemic process may sometimes involve a very early progenitor cell capable of both lymphoid and myeloid phenotypic differentiation. The heterogeneity of "null" ALL documented by this study may help to explain the variable clinical course and prognosis of these patients.

Antigens, Neoplasm↗

Recurrences of isolated leukemic hypopyon in a child with acute lymphoblastic leukemia.

The authors report follow-up observations for a case of isolated leukemic uveopathy that was first diagnosed in an 11-year-old girl shortly after cessation of treatment for acute lymphoblastic leukemia (ALL). Prior therapy for the complication included systemic antiblastic chemotherapy and low doses of radiation (3.9 Gy) to the affected eye. In July 1979, 2 months after chemotherapy was stopped for the second time, she presented with recurrent leukemic hypopyon in the left eye and was treated again with antiblastic chemotherapy followed in 1 year by high-dose (20 Gy) local irradiation. After a third recurrence, which was diagnosed as pre-B/B-cell ALL with a variable position of maturation arrest, enucleation was performed. The patient remains in complete remission for 26+ months after an additional course of systemic chemotherapy. This case illustrates the difficulty of eradicating leukemic cells from the eye with conventional treatment but suggests that a relapse in this site is not necessarily an ominous prognostic sign.

Adult↗

Biphenotypic Philadelphia positive, monosomy seven acute leukaemia: ultrastructural immunocytochemical study.

A case of Ph1 positive acute leukaemia is presented in which an additional chromosome change, monosomy 7 was found. There was no clinical evidence of a pre-existing chronic myeloid leukaemia. Cytochemistry and immunology showed a predominant HLA-DR+, TdT+, cALL- phenotype, with a small percentage of HLA-DR+, Leu-Ml+ and cALL- cells. The true biphenotypic nature of this case was clearly shown by transmission electron microscopy using the immunogold method combined with myeloperoxidase (MPO). Two distinct phenotypes, lymphoid (cALL+, MPO-) and myeloid (LeuMl+, MPO+) were identified with this technique. An immuno-scanning electron microscope technique was also used to study this case, which demonstrated the presence of two different surface morphologies.

Bone Marrow↗

Multimarker phenotypic characterization of adult and childhood acute lymphoblastic leukaemia: an Italian multicentre study.

A multicentre phenotypic study was carried out in Italy combining conventional immunological techniques with monoclonal antibody (MoAb) analysis in 190 cases of adult and childhood acute lymphoblastic leukaemia (ALL), in an attempt to define better the lineage relationship of the neoplastic cells. Of the 140 children evaluated, 79.3% expressed the common ALL (cALL) antigen (all analyses performed by MoAb), 11.4% were T-ALL and 9.3% were non-T, non-B, non-common ('null') ALL. The proportion of adult cALL cases was slightly lower (64% of the 50 cases studied) than that of childhood ALL, whilst the incidence of T-ALL was significantly higher in adults than in children (26% v. 11.4%, P less than 0.05). Because of the high proportion of cALL cases, the incidence of 'null' ALL in adult patients was similar (10%) to that of children, and lower than previously reported. The recognition of early pre-T-ALL cases (T1+, RFT2+, T10+, T6-, T11-, E-) contributed to the overall low proportion of 'null' ALL; prior to the use of MoAb, such cases would probably have been classified as undifferentiated acute leukaemia or 'null' ALL. The search for B-cell-related markers showed that the incidence of pre-B-ALL cases (cytoplasmic immunoglobulin positive cases) was similar in adults and in children (25.6% and 32%, respectively). Furthermore, the great majority of cases studied expressed the BA-1 antigen (92.8% of adults and 79% of children), whilst the BA-2 antigen was found in 53% of cases (tested only in children), confirming a hierarchy in the expression of B-cell related markers in cALL: BA-1, BA-2, CyIg. Several of the 'null' cases also expressed the BA-1 antigen on a variable proportion of cells, pointing to a possible B-cell origin of the blasts. This multicentre study shows that both in adult and in childhood ALL the combined use of conventional immunological markers and of a panel of MoAb allows identification of the cell lineage of the great majority of cases, thus reducing the number of 'null' ALL. Furthermore, these findings suggest that practically all cases of ALL belong either to the T or to the B cell compartment and that the neoplastic cells appear blocked at different levels along the lymphoid differentiation pathway.

Acute Disease↗

Scanning immunoelectron microscopy of hairy cell leukemia.

Scanning electron microscopy has shown a typical cell surface morphology in hairy cell leukemia. Scanning immunoelectron microscope techniques, utilizing monoclonal antibodies and colloidal gold particles, have recently become available. Eight patients with hairy cell leukemia have been studied with a panel of monoclonal antibodies of which B1, BA1, OKM1, anti-TAC and LeuM5 were shown to be suitable for scanning immunoelectron microscopy and reactive with hairy cells. The combination of typical cell surface features with reactivity for the B1 and LeuM5 monoclonal antibodies permits accurate diagnosis of hairy cell leukemia, particularly when low percentages of hairy cells are present as in hypocellular or in interferon-treated patients.

Antibodies, Monoclonal↗

Detection of the common acute lymphoblastic leukaemia antigen (CALLA) on B cells from human fetal tissues. A multiple phenotypic characterization.

Fetal bone marrow liver and spleen of gestational age 15-20 weeks contain CALLA+, HLA-DR+ lymphoid cells. We show that a proportion of them expresses surface membrane immunoglobulins (SIg) as well as B cell differentiation antigens. A multiple phenotypic analysis reveals that CALLA+ fetal B cells are: HLA-DR+, SIg+, FMC8+, BA1+, Y29.55+ or Y29.55-, B2+, TdT-. Tissue specific phenotypic differences concern the expression of B7 and HLA-DC on spleen but not on bone marrow B cells. This study indicates that the distribution of the CALL antigen across the B cell committed lineage is much wider in fetal than neonatal life since CALLA+B cells have not yet been detected in bone marrow and peripheral blood of normal infants and adults. In addition, the interpretation of our phenotypic data suggest that fetal bone marrow B cells are more immature than those present in the spleen, thus, further supporting the evidence that the bone marrow is the organ of B cell lymphopoiesis.

Antigens, Neoplasm↗

Effect of tumor-related factors on the in vivo and in vitro colony-forming ability of normal mouse marrow cells.

The effect of normal mouse marrow preincubation with Ehrlich tumor fluid (EAF) and Ehrlich tumor cell-conditioned medium (ET-CM) was investigated both on the in vivo assay for pluripotential stem cells (CFU-S) and on the in vitro assay for granulocytic-macrophagic progenitors (CFU-C). A significant reduction of the number of CFU-S was found when bone marrow cells were incubated with EAF. The morphological analysis showed a relative increase in the granulocytic type colonies besides an absolute increase in undifferentiated ones and an absolute decrease in erythroid colonies. The in vitro data show a decrease in CFU-C production, by stimulation with standard Colony Stimulating Factor (CSF), when the marrow cells are preincubated with EAF and ET-CM. When standard CAF (obtained from L-cells) is used at the higher concentrations, the CFU-C in the ET-CM treated marrow increases to the control values. EAF and ET-CM incubation also affects the CFU-C differentiation by increasing the number of pure granulocytic clones. The experimental data were discussed in order to explain an hypothesis about the activity of tumor-related factors.

Animals↗

Expression of the T1 (CD5, p67) surface antigen in B-CLL and B-NHL and its correlation with other B-cell differentiation markers.

The T1 surface antigen (CD5,p67) expression on blood lymphocytes (PBL) and lymphoid cells from lymph node biopsies (LN) from 31 patients with B-cell chronic lymphocytic leukemia (B-CLL) and 79 with B non-Hodgkin lymphoma (B-NHL), was detected in 25 B-CLL (80 per cent) and in 11 B-NHL (13 per cent) belonging to the following histologic subtypes: lymphocytic of CLL type (DLWD) one case, lymphoplasmacytoid (DLWD) four cases, centrocytic (DLPD) five cases, immunoblastic (DH) one case. All B-CLL and the T1 + B-NHL were also tested with monoclonal antibodies against the Common Acute Lymphoblastic Leukemia Antigen, B cells (FMC7, FMC8, BA1, Y29-55), T cells (OKT11a), HLA-DR and HLA-DQ monomorphic determinants. All the B-CLL and the T1+ B-NHL were CALLA-, BA1+, Y29.55+. FMC7+ cells were detected in large numbers six B-CLL (three T1+ and three T1-) and in four centrocytic lymphomas. FMC8 reacted with 70 per cent of leukemias (where it stained 30 per cent of neoplastic cells) and with 8/9 T+ B-NHL. HLA-DR and HLA-DQ molecules were detected in 100 per cent and 90 per cent of cases respectively. In vitro treatment of HLA-DQ- or T1- B-CLL with phorbol ester TPA led to the expression of these antigens as well as of the receptors for Interleukin 2 and MLR3 activation antigen. Surface membrane Ig (SIg) was detected in 79 per cent of cases, its density measured by FACS analysis varied, even markedly, from case to case. Among the B-CLL, cells with high SIg content were either T1+ or T1- and more likely FMC7+. The SIg- cases were seven B-CLL (five T1+ and two T1-) and two B-NHL, in which, however, cytoplasmic IgM was detected. This study reveals the existence of four major B-CLL subgroups: T1- SIg-, T1+ SIg+, T1+ SIg+, T1- SIg+. It also indicates that the T1 antigen may be transitionally present during B-cell differentiation and that its expression may precede that of SIg as supported by the in vitro studies. In addition, the finding that some B-NHL are T1+ suggests that they derive similarly to the B-CLL from a common progenitor.

Antibodies, Monoclonal↗

CEA and NCA expressed by colon carcinoma cells affect their interaction with and lysability by activated lymphocytes.

Heterogeneous lysability by interleukin-2 activated lymphocytes (LAK) and other immune effectors was observed in the human colon-carcinoma lines LoVo/Dx, LoVo/H and HT29. The tumor cells with high susceptibility to LAK (LoVo/Dx, HT29) expressed higher amounts of the adhesion molecules ICAMl, LFA3 and NCA/CEA than cells with low LAK sensitivity (LoVo/H). Monoclonal antibodies against these molecules caused a marked reduction of lysis by LAK of LoVo/Dx and HT29. A pool of these antibodies induced a nearly complete inhibition of the LAK lysis of both lines. Treatment of LoVo/Dx with differentiating agents (dimethylformamide and retinoic acid) led to a decreased expression of the adhesion molecules, including NCA, accompanied by increased resistance to LAK-mediated lysis. Moreover, the presence of CEA soluble antigen drastically inhibited the cytotoxic activity of LAK effectors against HT29 and LoVo/Dx cells, in a dose-dependent manner. These data indicate that sensitivity of colon-carcinoma cells to activated lymphocytes depends on the level of expression of adhesion molecules, including CEA and NCA. Given the role of CEA-related antigens in tumor/lymphocyte interaction, soluble CEA, frequently released by colon-carcinoma, may be involved in immunosuppressive effects induced in vivo by tumor cells.

Antigens, Neoplasm↗

Biological and clinical features of B-precursor childhood acute lymphoblastic leukemia showing CD2 and/or E-rosette co-expression.

BACKGROUND: Co-expression of the T-associated marker CD2 or E-rosette in non-T acute leukemia has rarely been reported. In this paper the incidence of such co-expression, together with its biologic features and clinical relevance, was evaluated in a large series of childhood "common" acute lymphoblastic leukemia (cALL) cases. METHODS: This analysis was performed retrospectively on 306 cases of childhood non-T ALL. CD2 and/or E-rosette co-expression with other non-T markers was usually shown by a clear overlap between the percentages of T and non-T markers, by the great difference between positivity for CD2 or E-rosette and other T markers, and by double staining for CD2 and CD10 in one case. Two cases were further studied by a panel of nine different CD2 monoclonal antibodies (MAbs) representative of different epitopes. DNA analysis for the configuration of Ig and TCR genes (beta, gamma, and delta locus) was carried out in three cases. RESULTS: Eleven out of 306 cases (3.6%) showed CD2 and/or E-rosette co-expression in otherwise typical cALL. Data obtained in two cases with the use of nine different CD2 Mabs showed a different pattern of reactivity between leukemic B cells and normal T cells. The configuration of Ig and TCR genes was compatible with B-lineage ALL. CONCLUSIONS: CD2 and/or E-rosette co-expression was observed in a small subset of acute leukemias showing immunophenotypic and genotypic features of B-lineage ALL. A pattern of reactivity different from that seen in normal T cells was observed in the two cases tested with a large panel of CD2 MAbs. No association was found with other known prognostic factors, and 8 of these 11 patients have been in first continuous remission for 36-93 months.

Antigens, Differentiation, T-Lymphocyte↗

Relevance of ultrastructural immunocytochemistry in the characterization of unclassifiable leukemias: correlation with phenotypic and genic studies.

Nine cases of acute leukemia presenting unusual phenotype were studied by light microscopy (LM) cytochemistry and transmission electron microscopy (TEM) immunocytochemistry with the immunogold staining (IGS) method; in addition, cytogenetic and molecular analyses were performed. The presence of myeloperoxidase (MPO) was studied at TEM in combination with immunophenotype to identify minor populations not characterizable at LM. Four of nine cases had no TEM/MPO reactivity, whereas the remaining five showed variable percentages of positive cells. Of the MPO negative cases, one was a megakaryoblastic leukemia with a positive platelet peroxidase (PPO) reaction, and three were lymphoid. Among the peroxidase positive cases, the percentage of MPO reactive cells was higher at TEM than at LM examination. In case 5 TEM analysis indicated that cells with some MPO reactivity at LM were non neoplastic myeloid cells. With this combined technique in cases 1 and 2 we excluded the presence of the MPO enzyme in CD15 positive lymphoid cells and, in another case, we documented the existence of CD19/MPO positive cells. The value of cytochemistry and immunology at the ultrastructural level for the characterization of blast cells and for the precise diagnosis of leukemia with "unusual" phenotype is illustrated.

Adult↗