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151. Expression of Vimentin Intermediate Filament Cytoskeleton in Acute Nonlymphoblastic Leukemias

Author

Dellagi, Koussay, Tabilio, Antonio, Portier, Marie-Madeleine, Vainchenker, William, Castaigne, Sylvie, Guichard, Josette, Breton-Gorius, Jeanine, and Brouet, Jean-Claude

Abstract

Since vimentin intermediate filament (IF) expression in hemopoietic cells varies with the cell lineage as well as the state of differentiation of the cells, we studied the vimentin cytoskeleton by direct immunofluorescence and electron microscopy in 50 cases of acute nonlymphocytic leukemias. We found that malignant cells tend to reproduce the vimentin organization characteristic of their normal cellular counterpart. Thus, in M2 and M3 leukemias (French-American-British classification), vimentin was often reduced to a juxtanuclear bundle of filaments contrasting with the rich filamentous network expressed by M4or M5 leukemias. In erythroblastic leukemias (M6) and mega- karyoblastic leukemias, both identified by the expression of lineage-specific antigens, the absence of vimentin IFs could be correlated with the level of differentiation reached by the blasts. M1 leukemias displayed an abnormal pattern of vimentin organization with aggregated filaments giving a ring-like structure. However, no abnormality of the vimentin polypeptide could be detected by two-dimen-sional electrophoresis. These results show that the expression of the vimentin IF cytoskeleton may be a useful marker of differentiation in the study of leukemic cells. © 1985 by Grune & Stratton, Inc.

Published
1985
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153. Successful engraftment of T-cell-depleted haploidentical 'three-loci' incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum

Author

Aversa, F, Tabilio, Antonio, Terenzi, A, Velardi, A, Falzetti, F, Giannoni, C, Iacucci, R, Zei, T, Martelli, Maria Paola, Gambelunghe, C, and Aristei, Cynthia

Subjects
Adult, Male, Adolescent, T-Lymphocytes, medicine.medical_treatment, Immunology, Graft vs Host Disease, ThioTEPA, Biochemistry, Lymphocyte Depletion, successful engraftment of T-cell, Granulocyte Colony-Stimulating Factor, Humans, Transplantation, Homologous, Medicine, Progenitor cell, Child, Bone Marrow Transplantation, Leukemia, business.industry, Graft Survival, Hematopoietic Stem Cell Transplantation, Immunosuppression, Cell Biology, Hematology, Middle Aged, Total body irradiation, Hematopoietic Stem Cells, medicine.disease, Recombinant Proteins, Granulocyte colony-stimulating factor, Transplantation, Treatment Outcome, surgical procedures, operative, medicine.anatomical_structure, Haplotypes, Host vs Graft Reaction, Histocompatibility, Female, Bone marrow, business, medicine.drug
Abstract

Patients who undergo transplantation with haploidentical “three-loci” mismatched T-cell-depleted bone marrow (BM) are at high risk for graft failure. To overcome the host-versus-graft barrier, we increased the size of the graft inoculum, which has been shown to be a major factor in controlling both immune rejection and stem cell competition in murine models. Seventeen patients (mean age, 23.2 years; range, 6 to 51 years) with end-stage chemoresistant leukemia were received transplants of a combination of BM with recombinant human granulocyte colony- stimulating factor-mobilized peripheral blood progenitor cells from HLA- haploidentical “three-loci” incompatible family members. The average concentration of colony-forming unit-granulocyte-macrophage in the final inoculum was sevenfold to 10-fold greater than that found in BM alone. The sole graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion of the graft by the soybean agglutination and E- rosetting technique. The conditioning regimen included total body irradiation in a single fraction at a fast dose rate, antithymocyte globulin, cyclophosphamide and thiotepa to provide both immunosuppression and myeloablation. One patient rejected the graft and the other 16 had early and sustained full donor-type engraftment. One patient who received a much greater quantity of T lymphocytes than any other patient died from grade IV acute GVHD. There were no other cases of GVHD > or = grade II. Nine patients died from transplant-related toxicity, 2 relapsed, and 6 patients are alive and event-free at a median follow-up of 230 days (range, 100 to 485 days). Our results show that a highly immunosuppressive and myeloablative conditioning followed by transplantation of a large number of stem cells depleted of T lymphocytes by soybean agglutination and E-rosetting technique has made transplantation of three HLA-antigen disparate grafts possible, with only rare cases of GVHD.

159. The Myeloperoxidase Gene in Acute Promyelocytic Leukemia

Author

Donti, Emilio, primary, Montanucci, Manuela, additional, Longo, Letizia, additional, Mencarelli, Amedea, additional, Pandolfi, Pierpaolo, additional, Tabilio, Antonio, additional, Nanni, Mauro, additional, Alimena, Giuliana, additional, Avanzi, Giancarlo, additional, Pegoraro, Luigi, additional, Grignani, Fausto, additional, and Pelicci, Pier Guiseppe, additional

Published
1989
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163. Treatment of High-Risk Acute Leukemia with T-Cell–Depleted Stem Cells from Related Donors with One Fully Mismatched HLA Haplotype.

Author

Aversa, Franco, Tabilio, Antonio, Velardi, Andrea, Cunningham, Isabel, Terenzi, Adelmo, Falzetti, Franca, Ruggeri, Loredana, Barbabietola, Giuliana, Aristei, Cynthia, Latini, Paolo, Reisner, Yair, Martelli, Massimo F., Felicini, Rita, Falcinelli, Flavio, Carotti, Alessandra, Perruccio, Katia, Ballanti, Stelvio, Santucci, Antonella, and Gambelunghe, Cesare

Subjects
*TRANSPLANTATION of organs, tissues, etc., *LEUKEMIA, *BONE marrow, *ACUTE leukemia, *GLOBULINS, *LYMPHOCYTES, *STEM cells, *HEMATOPOIETIC stem cells
Abstract

Background: In this study we tried to achieve successful transplantation in patients with acute leukemia with the use of hematopoietic stem cells from donors who shared only one HLA haplotype with the recipient (a “full-haplotype mismatch”). To prevent graft failure, large doses of T-cell–depleted hematopoietic stem cells were transplanted after a conditioning regimen of enhanced myeloablation and immunosuppression was administered to the recipient. Methods: Forty-three patients with high-risk acute leukemia who were scheduled for transplantation received total-body irradiation, thiotepa, fludarabine, and antithymocyte globulin. The graft consisted of peripheral-blood progenitor cells that had been mobilized in the donor with recombinant granulocyte colony-stimulating factor and also, in 28 cases, bone marrow. Bone marrow from the donor was depleted of T lymphocytes by processing with soybean agglutinin and E-rosetting. T-cell depletion of peripheral-blood mononuclear cells was achieved by E-rosetting followed by positive selection of CD34+ cells. No post-transplantation prophylaxis against graft-versus-host disease (GVHD) was administered. Results: In all the patients, full donor-type engraftment was achieved. In none of the patients who could be evaluated did acute or chronic GVHD develop. Regimen-related toxicity was minimal. Eleven of the 23 patients with acute lymphoblastic leukemia had a relapse, as did 2 of the 20 patients with acute myeloid leukemia. Transplantation-related mortality was 40 percent. After a median follow-up of 18 months (range, 8 to 30), 12 of the 43 patients were alive and free of disease. All surviving patients had a good quality of life. Conclusions: The main limitations of transplantation of bone marrow from donors who are matched with the recipient for only one HLA haplotype — GVHD and graft failure — can be overcome. Since most patients have a relative with one haplotype mismatch, advances in this method will increase the availability of hematopoietic-cell transplantation as curative therapy for acute leukemia. (N Engl J Med 1998;339:1186-93.) [ABSTRACT FROM AUTHOR]

Published
1998
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166. B-chronic lymphocytic leukemia cells exert an in vitro cytotoxicity mediated by tumor necrosis factor α

Author

Rosati, Emanuela, Sabatini, Rita, Tabilio, Antonio, Di Ianni, Mauro, Bartoli, Andrea, and Marconi, Pierfrancesco

Subjects
*TUMOR necrosis factors, *CYTOKINES, *GROWTH factors, *GLYCOPROTEINS
Abstract

Abstract: Tumor necrosis factor α (TNFα) is constitutively produced by B-chronic lymphocytic leukemia (B-CLL) cells and may act as an autocrine factor for their growth and survival. However, very few data are available on the possible cytotoxic effect of TNFα produced by B-CLL cells. This study investigated whether B-CLL cells exert in vitro cytotoxicity by TNFα and if so, whether this cytotoxicity can be modulated by cytokines. In 8 of 12 patients (66.6%), B-CLL cells in vitro constitutively produced TNFα and exerted a TNFα-mediated cytotoxicity, evaluated in an 18-h 51Cr release assay, against the TNFα-sensitive Jurkat, U937 and K562 cell lines but not against the TNFα-resistant Raji cell line. Involvement of TNFα in B-CLL cell cytotoxicity is demonstrated by the fact that anti-TNFα antibodies strongly inhibited it and supernatants of cytotoxic cultures contained TNFα and mediated a completely TNFα-dependent cytotoxicity. When the cytotoxic B-CLL cells were stimulated with interleukin (IL)-2 plus IL-12, there was increased TNFα mRNA expression, TNFα production and TNFα-mediated cytotoxicity. All eight patients with cytotoxic leukemic cells had progressive disease and six of these also expressed high levels of ZAP-70 protein. In the other four patients (33.3%), B-CLL cells did not produce TNFα in vitro and were not cytotoxic, either spontaneously or after IL-2 plus IL-12 stimulation. Of these four patients, three had stable disease and one had progressive disease. The patient with progressive disease and one of the three with stable disease expressed low levels of ZAP-70 protein. We conclude that a group of B-CLL patients with progressive disease have leukemic B cells able to exert in vitro a TNFα-mediated cytotoxicity, which is modulated by cytokines. [Copyright &y& Elsevier]

Published
2005
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167. Thymus-Independent T Cell Differentiation in Vitro

Author

Sanchez, Massimo, Alfani, Elena, Visconti, Giovannella, Passarelli, Anna Maria, Migliaccio, Anna Rita, Migliaccio, Giovanni, Abraham, Nader G., editor, Tabilio, Antonio, editor, Martelli, Massimo, editor, Asano, Shigetaka, editor, and Donfrancesco, Alberto, editor

Published
1999
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169. Immunogenetics Problems in Cord Blood Transplantation

Author

Poli, Francesca, Diomelli, Barbara, Ghidoli, Nadia, Tettamanti, Cristina, Macchi, Barbara, Scalamogna, Mario, Sirchia, Girolamo, Abraham, Nader G., editor, Tabilio, Antonio, editor, Martelli, Massimo, editor, Asano, Shigetaka, editor, and Donfrancesco, Alberto, editor

Published
1999
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170. Presence Of B Cell Progenitors In the Thymus

Author

Inaba, Muneo, Mori, Shin-Ichiro, Sugihara, Akira, Feng, Biao, Ito, Tomoki, Inaba, Kayo, Ikehara, Susumu, Abraham, Nader G., editor, Tabilio, Antonio, editor, Martelli, Massimo, editor, Asano, Shigetaka, editor, and Donfrancesco, Alberto, editor

Published
1999
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171. Iron Chelation in Cancer Therapy

Author

Torti, Suzy V., Planalp, R. P., Brechbiel, M. W., Park, G., Torti, F. M., Abraham, Nader G., editor, Tabilio, Antonio, editor, Martelli, Massimo, editor, Asano, Shigetaka, editor, and Donfrancesco, Alberto, editor

Published
1999
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176. The Hereditary Hemochromatosis Gene and Iron Homeostasis

Author

Feder, J. N., Penny, D. M., Irrinki, A., Mintier, G. A., Lebron, J. A., Gross, C. N., Lee, L., Tsuchihashi, Z., Enns, C. A., Bjorkman, P. J., Schatzman, R. C., Abraham, Nader G., editor, Tabilio, Antonio, editor, Martelli, Massimo, editor, Asano, Shigetaka, editor, and Donfrancesco, Alberto, editor

Published
1999
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188. Hematological Aspects of Common Marmoset Monkey Transplanted with Autologous MDR1 Gene Transduced Peripheral Blood Stem Cells

Author

Tani, Kenzaburo, Hibino, Hitoshi, Sugiyama, Hajime, Wu, Ming-Shiuan, Izawa, Kiyoko, Tanabe, Tsuyoshi, Hase, Hidenori, Nakazaki, Yukoh, Ishii, Hajime, Suzuki, Shuzo, Tanioka, Yoshikuni, Sugimoto, Yoshikazu, Asano, Shigetaka, Abraham, Nader G., editor, Tabilio, Antonio, editor, Martelli, Massimo, editor, Asano, Shigetaka, editor, and Donfrancesco, Alberto, editor

Published
1999
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190. Identification and Characterization of Constitutively Active Stat5

Author

Nosaka, Tetsuya, Onishi, Mayumi, Kawashima, Toshiyuki, Yamada, Koji, Misawa, Kazuhide, Ariyoshi, Kouichi, Towatari, Masayuki, Saito, Hidehiko, Tani, Kenzaburo, Asano, Shigetaka, Miyajima, Atsushi, Kitamura, Toshio, Abraham, Nader G., editor, Tabilio, Antonio, editor, Martelli, Massimo, editor, Asano, Shigetaka, editor, and Donfrancesco, Alberto, editor

Published
1999
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197. Genetic Heterogeneity in Ewing Tumors and Neuroblastomas

Author

Ambros, P. F., Ambros, I. M., Amann, G., Hattinger, C. M., Ladenstein, R., Kerbl, R., Rumpler, S., Luegmayr, A., Gadner, H., Abraham, Nader G., editor, Tabilio, Antonio, editor, Martelli, Massimo, editor, Asano, Shigetaka, editor, and Donfrancesco, Alberto, editor

Published
1999
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199. Towards Vaccination with Defined Tumor Antigens?

Author

van der Bruggen, P., Chaux, P., Mandruzzato, S., Van den Eynde, B., Coulie, P. G., Marchand, M., Boon, T., Abraham, Nader G., editor, Tabilio, Antonio, editor, Martelli, Massimo, editor, Asano, Shigetaka, editor, and Donfrancesco, Alberto, editor

Published
1999
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