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4. Standardization of molecular monitoring of CML : results and recommendations from the European treatment and outcome study

Author

White HE, Salmon M, Albano F, Andersen CSA, Balabanov S, Balatzenko G, Barbany G, Cayuela JM, Cerveira N, Cochaux P, Colomer D, Coriu D, Diamond J, Dietz C, Dulucq S, Engvall M, Franke GN, Gineikiene-Valentine E, Gniot M, Gómez-Casares MT, Gottardi E, Hayden C, Hayette S, Hedblom A, Ilea A, Izzo B, Jiménez-Velasco A, Jurcek T, Kairisto V, Langabeer SE, Lion T, Meggyesi N, Mešanović S, Mihok L, Mitterbauer-Hohendanner G, Moeckel S, Naumann N, Nibourel O, Oppliger Leibundgut E, Panayiotidis P, Podgornik H, Pott C, Rapado I, Rose SJ, Schäfer V, Touloumenidou T, Veigaard C, Venniker-Punt B, Venturi C, Vigneri P, Vorkinn I, Wilkinson E, Zadro R, Zawada M, Zizkova H, Müller MC, Saussele S, Ernst T, Machova Polakova K, Hochhaus A, Cross NCPa 62, Andreas Hochhaus 52, Nicholas C P Cross, White, He, Salmon, M, Albano, F, Andersen, Csa, Balabanov, S, Balatzenko, G, Barbany, G, Cayuela, Jm, Cerveira, N, Cochaux, P, Colomer, D, Coriu, D, Diamond, J, Dietz, C, Dulucq, S, Engvall, M, Franke, Gn, Gineikiene-Valentine, E, Gniot, M, Gómez-Casares, Mt, Gottardi, E, Hayden, C, Hayette, S, Hedblom, A, Ilea, A, Izzo, B, Jiménez-Velasco, A, Jurcek, T, Kairisto, V, Langabeer, Se, Lion, T, Meggyesi, N, Mešanović, S, Mihok, L, Mitterbauer-Hohendanner, G, Moeckel, S, Naumann, N, Nibourel, O, Oppliger Leibundgut, E, Panayiotidis, P, Podgornik, H, Pott, C, Rapado, I, Rose, Sj, Schäfer, V, Touloumenidou, T, Veigaard, C, Venniker-Punt, B, Venturi, C, Vigneri, P, Vorkinn, I, Wilkinson, E, Zadro, R, Zawada, M, Zizkova, H, Müller, Mc, Saussele, S, Ernst, T, Machova Polakova, K, Hochhaus, A, Cross NCPa, 62, Andreas Hochhaus, 52, and Nicholas C, P Cross

Subjects
Cancer Research, Cancer och onkologi, Fatigue Syndrome, Chronic, Fusion Proteins, bcr-abl, 610 Medicine & health, Hematology, Reference Standards, Treatment Outcome, Oncology, hemic and lymphatic diseases, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Cancer and Oncology, Humans, Hematologi
Abstract

Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1IS and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.

Published
2022

5. LABNET AML: AN EFFICIENT NETWORK THAT CONNECTS HEMATOLOGY CENTERS AND LABORATORIES FOR A HIGH-LEVEL DIAGNOSTIC/PROGNOSTIC WORKUP OF AML

Author

Voso, M, Cucci, R, Messina, M, Santoro, A, Divona, M, Albano, F, Ottaviani, E, Bertorelle, R, Guerrasio, A, Gottardi, E, Izzo, B, Tarantini, G, Scardocci, A, Siragusa, S, Forghieri, F, Cairoli, R, Cambo, B, Vallisa, D, Venditti, A, Ferrara, F, Mannina, D, Cilloni, D, La, S, Piciocchi, A, Falini, B, Pane, F, Saglio, G, Vignetti, M, Amadori, S, Voso MT, Cucci R, Messina M, Santoro A, Divona M, Albano F, Ottaviani E, Bertorelle R, Guerrasio A, Gottardi E, Izzo B, Tarantini G, Scardocci A, Siragusa S, Forghieri F, Cairoli R, Cambo B, Vallisa D, Venditti A, Ferrara F, Mannina D, Cilloni D, La SalaE, Piciocchi A, Falini B, Pane F, Saglio G, Vignetti M, Amadori S, Voso, M, Cucci, R, Messina, M, Santoro, A, Divona, M, Albano, F, Ottaviani, E, Bertorelle, R, Guerrasio, A, Gottardi, E, Izzo, B, Tarantini, G, Scardocci, A, Siragusa, S, Forghieri, F, Cairoli, R, Cambo, B, Vallisa, D, Venditti, A, Ferrara, F, Mannina, D, Cilloni, D, La, S, Piciocchi, A, Falini, B, Pane, F, Saglio, G, Vignetti, M, Amadori, S, Voso MT, Cucci R, Messina M, Santoro A, Divona M, Albano F, Ottaviani E, Bertorelle R, Guerrasio A, Gottardi E, Izzo B, Tarantini G, Scardocci A, Siragusa S, Forghieri F, Cairoli R, Cambo B, Vallisa D, Venditti A, Ferrara F, Mannina D, Cilloni D, La SalaE, Piciocchi A, Falini B, Pane F, Saglio G, Vignetti M, and Amadori S

Published
2021

8. LABNET AML: AN EFFICIENT NETWORK THAT CONNECTS HEMATOLOGY CENTERS AND LABORATORIES FOR A HIGH-LEVEL DIAGNOSTIC/PROGNOSTIC WORKUP OF AML

Author

Voso, M. T., Cucci, R., Messina, M., Santoro, A., Divona, M., Albano, F., Ottaviani, E., Roberta Bertorelle, Guerrasio, A., Gottardi, E., Izzo, B., Tarantini, G., Scardocci, A., Siragusa, S., Forghieri, F., Cairoli, R., Cambo, B., Vallisa, D., Venditti, A., Ferrara, F., Mannina, D., Cilloni, D., La Sala, E., Piciocchi, A., Falini, B., Pane, F., Saglio, G., Vignetti, M., Amadori, S., Voso, M, Cucci, R, Messina, M, Santoro, A, Divona, M, Albano, F, Ottaviani, E, Bertorelle, R, Guerrasio, A, Gottardi, E, Izzo, B, Tarantini, G, Scardocci, A, Siragusa, S, Forghieri, F, Cairoli, R, Cambo, B, Vallisa, D, Venditti, A, Ferrara, F, Mannina, D, Cilloni, D, La, S, Piciocchi, A, Falini, B, Pane, F, Saglio, G, Vignetti, M, and Amadori, S

Subjects
Hematology
Published
2021

9. Increased Tumour Burden over a 36 Month Period in Chronic Myeloid Leukemia Patients Following Imatinib Discontinuation: Role of Digital PCR

Author

Diral, E, Le Coutre, P, Gottardi, E, Elena, C, Bergamaschi, M, Assouline, S, Di Bona, E, Petiti, J, Stagno, F, Iurlo, A, Kim, D, Pirola, A, Bonanomi, M, Crivori, P, Piazza, R, Fava, C, Gambacorti-Passerini, C, Diral E., Le Coutre P., Gottardi E. M., Elena C., Bergamaschi M., Assouline S., Di Bona E., Petiti J., Stagno F., Iurlo A., Kim D. -W., Pirola A., Bonanomi M. L., Crivori P., Piazza R., Fava C., Gambacorti-Passerini C., Diral, E, Le Coutre, P, Gottardi, E, Elena, C, Bergamaschi, M, Assouline, S, Di Bona, E, Petiti, J, Stagno, F, Iurlo, A, Kim, D, Pirola, A, Bonanomi, M, Crivori, P, Piazza, R, Fava, C, Gambacorti-Passerini, C, Diral E., Le Coutre P., Gottardi E. M., Elena C., Bergamaschi M., Assouline S., Di Bona E., Petiti J., Stagno F., Iurlo A., Kim D. -W., Pirola A., Bonanomi M. L., Crivori P., Piazza R., Fava C., and Gambacorti-Passerini C.

Published
2019

10. The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview

Author

Baccarani, M, Castagnetti, F, Gugliotta, G, Rosti, G, Soverini, S, Albeer, A, Pfirrmann, M, Bekadja, Ma, Entasoltan, B, Nachi, M, Elghandour, A, El Sorady, M, Abdelfattah, R, El Nahass, Y, Samra, M, Azzazi, M, Elsobki, E, Moussa, M, Fahmy, O, Mattar, M, Shehata, Azmy, Se, (Azmy, E, 9 ), Emad), Bolarinwa, (Bolarinwa, Ra, ( 10 ), Rahman A., Eid, (Eid, S, Samir)( 11, ), Khelif, (Khelif, A, Abderrhaim)( 11, ), Hached, (Hached, F, Farhat)( 11, ), Menif, (Menif, S, Samia)( 12, ), Rahman, (Rahman, H, Hafizur)( 13, ), Huang, (Huang, Xj, Xiaojun)(, 14, 15, ), Jiang, (Jiang, Q, Qian)(, 14, (Ye, Yx, Yuanxin)( 16, ), Zhu, (Zhu, Hl, Huanling)( 16, ), Chen, (Chen, Sn, Suning)( 17, ), Varma, (Varma, N, Neelam)( 18, ), Ganesan, (Ganesan, P, Prasanth)( 19, ), Gundeti, (Gundeti, S, Sadashivudu)( 20, ), Malhotra, (Malhotra, H, Hemant)( 21, ), Radhakrishnan, (Radhakrishnan, Vs, ( 22 ), Vivek S., Kumar, (Kumar, L, Lalit)( 23, ), Sharawat, (Sharawat, Sk, Surender Kumar)( 23, ), Seth, (Seth, T, Tulika)( 24, ), Ausekar, (Ausekar, Bv, ( 25 ), B. V., Balasubramanian, (Balasubramanian, P, Poonkuzhali)( 26, ), Poopak, (Poopak, B, Behzad)(, 27, 28, ), Inokuchi, (Inokuchi, K, Koiti)( 29, ), Kim, (Kim, Dw, Dong-Wook)( 30, ), Kindi, Al, S (Al Kindi, Salam)( 31, ), Mirasol, (Mirasol, A, Angelina)( 32, ), Qari, (Qari, M, Mohammed)( 33, ), Goh, (Goh, Yt, Yeow Tee)( 34, ), Shih, (Shih, Ly, Lee-Yung)(, 35, 36, ), Branford, (Branford, S, Susan)(, 37, 38, ), Lion, (Lion, T, Thomas)( 39, ), Valent, (Valent, P, Peter)( 40, ), Burgstaller, (Burgstaller, S, Sonja)( 41, ), Thaler, (Thaler, J, Joseph)( 41, ), Labar, (Labar, B, Boris)( 42, ), Zadro, (Zadro, R, Renata)( 42, ), Mayer, (Mayer, J, Jiri)(, 43, 44, ), Zackova, (Zackova, D, Daniela)(, 43, Faber, (Faber, E, Edgar)( 45, ), Pallisgaard, (Pallisgaard, N, Niels)( 46, ), Xavier-Mahon, (Xavier-Mahon, F, Francois)( 47, ), Lippert, (Lippert, E, Eric)( 48, ), Cayuela, (Cayuela, Jm, Jean Michel)( 49, ), Rea, (Rea, D, Delphine)( 49, ), Millot, (Millot, F, Frederic)( 50, ), Suttorp, (Suttorp, M, Meinolf)( 51, ), Hochhaus, (Hochhaus, A, Andreas)( 52, ), Niederwieser, (Niederwieser, D, Dietger)( 53, ), Saussele, (Saussele, S, Susanne)( 54, ), Haferlach, (Haferlach, T, Torsten)( 55, ), Jeromine, (Jeromine, S, Sabine)( 55, ), Panayiotidis, (Panayiotidis, P, Panayiotis)(, 56, 57, ), Conneally, (Conneally, E, Eibhlin)( 58, ), Langabeer, (Langabeer, S, Steve)( 58, ), Nagler, (Nagler, A, Arnon)(, 59, 60, ), Rupoli, (Rupoli, S, Serena)( 61, ), Santoro, (Santoro, N, Nicola)( 62, ), Albano, (Albano, F, Francesco)( 63, ), Castagnetti, (Castagnetti, F, Fausto), Ottaviani, (Ottaviani, E, Emanuela)(, 64, 65, ), Rambaldi, (Rambaldi, A, Alessandro)(, 66, 67, ), Stagno, (Stagno, F, Fabio)( 68, ), Molica, (Molica, S, Stefano)( 69, ), Biagiotti, (Biagiotti, C, Caterina)( 70, ), Scappini, (Scappini, B, Barbara)( 70, ), Lemoli, (Lemoli, R, Roberto)( 71, ), Iurlo, (Iurlo, A, Alessandra)(, 72, 73, ), Pungolino, (Pungolino, E, Ester)( 74, ), Menna, (Menna, G, Giuseppe), Pane, (Pane, F, Fabrizio)( 76, ), Gottardi, (Gottardi, E, Enrico)(, 77, 78, ), Rege-Cambrin, (Rege-Cambrin, G, Giovanna)(, 77, Binotto, (Binotto, G, Gianni)( 79, ), Putti, (Putti, Mc, Maria Caterina)( 80, ), Falzetti, (Falzetti, F, Franca)( 81, ), Visani, (Visani, G, Giuseppe)( 82, ), Galimberti, (Galimberti, S, Sara)( 83, ), Musto, (Musto, P, Pellegrino)( 84, ), Abruzzese, (Abruzzese, E, Elisabetta)( 85, ), Breccia, (Breccia, M, Massimo)( 86, ), Giona, (Giona, F, Fiorina)( 86, ), Chiusolo, (Chiusolo, P, Patrizia)( 87, ), Sica, (Sica, S, Simona)( 87, ), Fava, (Fava, C, Carmen)( 88, ), Ferrero, (Ferrero, D, Dario)( 88, ), Tiribelli, (Tiribelli, M, Mario)( 89, ), Bonifacio, (Bonifacio, M, Massimiliano)( 90, ), Griskevicius, (Griskevicius, L, Laimonas)( 91, ), Musteata, (Musteata, V, Vasile)( 92, ), Janssen, (Janssen, J, Jeroen)( 93, ), Prejzner, (Prejzner, W, Witold)( 94, ), Sacha, (Sacha, T, Tomasz)( 95, ), Waclaw, (Waclaw, J, Joanna)( 95, ), Almeida, (Almeida, Am, Antonio Medina)( 96, ), Kulikov, (Kulikov, S, Sergei)( 97, ), Turkina, (Turkina, A, Anna)( 97, ), Bogdanovic, (Bogdanovic, A, Andrija)( 98, ), Zupan, (Zupan, I, Irena)( 99, ), Marce, (Marce, S, Silvia)( 100, ), Cervantes, (Cervantes, F, Francisco)( 101, ), Steegmann, (Steegmann, Jl, Juan Luis)( 102, ), Kotlyarchuk, (Kotlyarchuk, K, Konstyantyn)( 103, ), Milner, (Milner, Bj, ( 104 ), Benedict J., Rose, (Rose, S, Susan)( 105, ), Clench, (Clench, T, Tim)( 106, ), Waits, (Waits, P, Paula)( 107, ), Austin, (Austin, S, Steve)( 108, ), Wickham, (Wickham, C, Caroline)( 109, ), Clark, (Clark, R, Richard)( 110, ), Apperley, (Apperley, J, Jane), Claudiani, (Claudiani, S, Simone)( 111, ), Foroni, (Foroni, L, Letizia)( 111, ), Szydlo, (Szydlo, R, Richard)( 111, ), Burt, (Burt, E, Emma)( 112, ), Bescoby, (Bescoby, R, Ruth)( 113, ), Cork, (Cork, L, Leanne)( 113, ), O'Brien, (O'Brien, S, Stephen)( 113, ), Green, (Green, B, Bethaney)( 114, ), Hawtree, (Hawtree, S, Sarah)( 114, ), Watson, (Watson, M, Mark)( 114, ), Bengio, (Bengio, Rm, Raquel Maria)( 115, ), Larripa, (Larripa, I, Irene)( 115, ), Pavlovsky, (Pavlovsky, C, Carolina)( 116, ), Moiraghi, (Moiraghi, B, Beatriz)( 117, ), Pinna, De, CAR (Requiao de Pinna, Cristiane Almeida)( 118, ), Magalhaes, GHR (Romani Magalhaes, Gustavo Henrique)( 119, ), Pagnano, (Pagnano, K, Katia)( 120, ), Funke, (Funke, V, Vaneuza)( 121, ), Tavares, (Tavares, Rs, Renato Sampaio)( 122, ), Prado, (Prado, A, Adriana)( 123, ), Azevedo, (Azevedo, Aa, Alita Andrade)( 124, ), Fogliatto, (Fogliatto, L, Laura)( 125, ), Bonecker, (Bonecker, S, Simone)( 126, ), Centrone, (Centrone, R, Renato)( 127, ), Moellman, (Moellman, A, Artur)( 128, ), Conchon, (Conchon, M, Monika)( 130, ), Centurion, (Centurion, Me, Maria Elida)( 131, ), (Prado, Ai, Ana-Ines)( 132, ), Lopez, (Lopez, Jl, ( 133 ), J. L., Petruzziello, (Petruzziello, F, Fara)( 75, ), Bendit, (Bendit, I, Israel), Baccarani M., Castagnetti F., Gugliotta G., Rosti G., Soverini S., Albeer A., and Pfirrmann M.

Subjects
Male, 0301 basic medicine, Cancer Research, bcr-abl, Fusion Proteins, bcr-abl, Global Health, 0302 clinical medicine, hemic and lymphatic diseases, 80 and over, Odds Ratio, Prevalence, Age Factor, Chronic, Young adult, Child, MOLECULAR RESPONSE, Leukemic, Aged, 80 and over, Leukemia, Hematology, Gene Expression Regulation, Leukemic, CHRONIC MYELOGENOUS LEUKEMIA, Age Factors, Myeloid leukemia, Middle Aged, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Female, Life Sciences & Biomedicine, Human, Adult, Transcriptional Activation, medicine.medical_specialty, Adolescent, Immunology, IMATINIB MESYLATE, DENDRITIC CELLS, CML PATIENTS, Young Adult, 03 medical and health sciences, Myelogenous, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, medicine, Humans, 1112 Oncology and Carcinogenesis, BCR/ABL TRANSCRIPT, Preschool, CYTOGENETIC RESPONSE, Aged, Science & Technology, CHRONIC-PHASE, business.industry, Infant, Newborn, Fusion Proteins, ABL FUSION PROTEINS, P190 BCR-ABL, Infant, 1103 Clinical Sciences, Odds ratio, Newborn, medicine.disease, International BCR-ABL Study Group, Settore MED/15 - MALATTIE DEL SANGUE, 030104 developmental biology, Imatinib mesylate, Gene Expression Regulation, BCR-ABL Positive, business, Chronic myelogenous leukemia
Abstract

There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia. Their frequency has never been systematically investigated. In a series of 45503 newly diagnosed CML patients reported from 45 countries, it was found that the proportion of e13a2 (also known as b2a2) and of e14a2 (also known as b3a2), including the cases co-expressing e14a2 and e13a2, was 37.9% and 62.1%, respectively. The proportion of these two transcripts was correlated with gender, e13a2 being more frequent in males (39.2%) than in females (36.2%), was correlated with age, decreasing from 39.6% in children and adolescents down to 31.6% in patients ≥ 80 years old, and was not constant worldwide. Other, rare transcripts were reported in 666/34561 patients (1.93%). The proportion of rare transcripts was associatedwith gender (2.27% in females and 1.69% in males) and with age (from 1.79% in children and adolescents up to 3.84% in patients ≥ 80 years old). These data show that the differences in proportion are not by chance. This is important, as the transcript type is a variable that is suspected to be of prognostic importance for response to treatment, outcome of treatment, and rate of treatment-free remission.

Published
2019

21. Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease: Report of the BIOMED-1 Concerted Action: Investigation of minimal residual disease in acute leukemia

Author

van Dongen, JJM, Macintyre, EA, Gabert, JA, Delabesse, E, Rossi, V, Saglio, G, Gottardi, E, Rambaldi, A, Dotti, G, Griesinger, F, Parreira, A, Gameiro, P, Diáz, M González, Malec, M, Langerak, AW, San Miguel, JF, and Biondi, A

Published
1999
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31. Molecular response to imatinib in late chronic-phase chronic myeloid leukemia

Author

ROSTI G, MARTINELLI G, BASSI S, AMABILE M, TRABACCHI E, GIANNINI B, CILLONI D, IZZO, BARBARA, DE VIVO A, TESTONI N, CAMBRIN GR, BONIFAZI F, SOVERINI S, LUATTI S, GOTTARDI E, ALBERTI D, PANE, FABRIZIO, SALVATORE F, SAGLIO G, BACCARANI M, STUDY COMMITTEE, ITALIAN COOPERATIVE STUDY GROUP FOR CHRONIC MYELOID LEUKEMIA, WRITING COMMITTEE, ITALIAN COOPERATIVE STUDY GROUP FOR CHRONIC MYELOID L.E.U.K.E.M.I.A., ROSTI G., MARTINELLI G., BASSI S., AMABILE M., TRABACCHI E., GIANNINI B., CILLONI D., IZZO B., DE VIVO A., TESTONI N., CAMBRIN G. R., BONIFAZI F., SOVERINI S., LUATTI S., GOTTARDI E., ALBERTI D., PANE F., SALVATORE F., SAGLIO G., BACCARANI M., STUDY COMMITTEE, ITALIAN COOPERATIVE STUDY GROUP ON CHRONIC MYELOID LEUKEMIA, WRITING COMMITTEE, Rosti, G, Martinelli, G, Bassi, S, Amabile, M, Trabacchi, E, Giannini, B, Cilloni, D, Izzo, Barbara, DE VIVO, A, Testoni, N, Cambrin, Gr, Bonifazi, F, Soverini, S, Luatti, S, Gottardi, E, Alberti, D, Pane, Fabrizio, Salvatore, F, Saglio, G, Baccarani, M, Study, Committee, ITALIAN COOPERATIVE STUDY GROUP FOR CHRONIC MYELOID, Leukemia, Writing, Committee, and ITALIAN COOPERATIVE STUDY GROUP FOR CHRONIC MYELOID, L. E. U. K. E. M. I. A.

Subjects
POLYMERASE-CHAIN-REACTION, Immunology, IMATINIB MESYLATE, Alpha interferon, Antineoplastic Agents, Bone Marrow Cells, INTERFERON-ALPHA THERAPY, Genes, abl, PHILADELPHIA-CHROMOSOME, Biochemistry, Piperazines, Myelogenous, Recurrence, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, Humans, Medicine, CHRONIC MYELOGENOUS LEUKEMIA, TYROSINE KINASE INHIBITOR, MINIMAL-RESIDUAL-DISEASE, BONE-MARROW-TRANSPLANTATION, FUSION GENE TRANSCRIPTS, ABL-POSITIVE CELLS, BCR-ABL, Philadelphia-positive, MOLECULAR RESPONSE, CHRONIC MYELOID LEUKEMIA, ABL, business.industry, breakpoint cluster region, Myeloid leukemia, Imatinib, Cell Biology, Hematology, medicine.disease, Leukemia, Pyrimidines, Treatment Outcome, Imatinib mesylate, Benzamides, Cancer research, beta 2-Microglobulin, business, Follow-Up Studies, medicine.drug
Abstract

Imatinib is a tyrosine-kinase inhibitor that binds to ABL proteins and induces cytogenetic remissions in patients with chronic myeloid leukemia (CML). In these patients measuring response by molecular techniques is clearly required. We determined the cytogenetic and molecular response (CgR, MR) to imatinib in 191 patients with late chronic-phase Philadelphia-positive (Ph+) CML, previously treated with interferon α. MR was assessed with real-time quantitative (TaqMan) reverse transcription–polymerase chain reaction and was expressed as the ratio between BCR/ABL and β2-microglobulin × 100, the lowest level of detectability of the method being 0.00001. A complete CgR (CCgR) was achieved in 85 (44%) of 191 patients and was maintained for 2 years in 67 (79%) of 85 patients. A reduction of the transcript level of more than 2 logs was achieved in all but 9 patients with CCgR versus none of 23 with partial CgR. In the CCgRs the median value of the MR was 0.0008 after 12 months and 0.0001 after 24 months, with the transcript level undetectable in 22 cases. We conclude that in CCgRs the degree of MR may vary from 2 to more than 4 logs, and that there is a progressive decrease of transcript level by time. Only 1 of 22 negative cases has had a relapse as yet.

Published
2004

32. Aproveitamento do resíduo de beneficiamento de rochas ornamentais e de escória de aciaria moída como fíler em pavimentos de concreto asfáltico

Author

GOTTARDI, E. V., Jamilla Lutif Teixeira, Georgia Serafim Araújo, PIRES, P. J. M., and CALMON, J.L.

Abstract

Made available in DSpace on 2016-08-29T15:10:20Z (GMT). No. of bitstreams: 1 tese_9435_Eduardo valadares.pdf: 3899470 bytes, checksum: a3f7d637f4e68750197785e9a06bed05 (MD5) Previous issue date: 2015-07-29 O Estado do Espírito Santo tem o maior complexo de pelotização de minério de ferro do mundo e é o maior produtor nacional de placas de aço. É, além disso, o maior exportador de mármore e granito da América Latina. O estado lidera a extração nacional de mármore e granito ornamentais, sendo responsável por 39% das exportações brasileiras de rochas ornamentais e por 50% de placas de mármore beneficiadas. Em contrapartida, o estado produz um grande volume de rejeitos industrial tais como escória de aciaria e resíduo de beneficiamento de rochas ornamentais. Muitos trabalhos científicos têm estudado formas de empregar estes rejeitos na pavimentação. Diante do exposto, este trabalho visa contribuir nesta temática avaliando o comportamento mecânico de concretos asfálticos produzidos com a incorporação de Resíduos de Beneficiamento de Rochas Ornamentais (RBRO) e de Escória Moída de Aciaria (EMA) como fíler. Um total de 11 misturas foram estudadas, variando-se entre elas o percentual e o tipo de resíduo adicionado. Através da metodologia Marshall, determinou-se o teor de ligante de projeto das misturas em estudo. Para caracterização mecânica das misturas foram realizados ensaios de estabilidade e fluência Marshall, resistência à tração por compressão diametral, desgaste Cântabro e dano por umidade (Ensaio de Lottman Modificado). Os resultados mostram que a adição dos resíduos no traço comercial de CBUQ mantem tanto os parâmetros volumétricos como o comportamento mecânico das misturas com utilização dos resíduos industriais praticamente inalterados quando comparados à mistura de referência e que atendem aos requisitos das especificações vigentes do DNIT. Conclui-se, portanto, que a utilização de resíduos industriais em misturas asfálticas se apresenta como uma alternativa promissora para reaproveitamento dos rejeitos estudados.

Published
2015

34. Hepatic expression of hemochromatosis genes in two mouse strains after phlebotomy and iron overload

Author

Bondi A, Valentino P, Daraio F, Paolo Ettore Porporato, Gramaglia E, Carturan S, Gottardi E, Camaschella C, Roetto A, Bondi, A, Valentino, P, Daraio, F, Porporato, P, Gramaglia, E, Carturan, S, Gottardi, E, Camaschella, Clara, and Roetto, A.

Subjects
Mice, Inbred C57BL, Mice, Iron Overload, Gene Expression Regulation, Liver, Phlebotomy, Species Specificity, Mice, Inbred DBA, Animals, Female, Hemochromatosis, Cation Transport Proteins
Abstract

Iron homeostasis is tightly regulated in mammals according to the needs of erythropoiesis and the iron stores present. This regulation is disrupted in hereditary hemochromatosis (HH), a genetic disorder characterized by increased intestinal iron absorption, leading to iron overload. The genes coding for HFE, transferrin receptor 2 (TFR2), ferroportin (SLC40A1 or FPN1), hepcidin (HEPC) and hemojuvelin (HJV or RGMC) are responsible for different types of genetic iron overload. All these genes are highly expressed in the liver and their protein products are likely components of a single hepcidin-related pathway. In order to gain insights into the molecular relationship among the HH proteins we evaluated the hepatic expression of HH genes in conditions of iron restriction or overload.Data were obtained after phlebotomy, to activate the erythroid regulators and following parenteral iron dextran loading, to activate the store regulators, in two mice strains (C57BL/6 and DBA/2). HH genes and proteins expression were analyzed by quantitative real time polymerase chain reaction and by Western blotting, respectively.Hepc RNA was reduced after phlebotomy and increased in iron overload. A statistically significant reduction of hepatic Fpn1 RNA expression was observed after phlebotomy; this effect was more evident in the DBA/2 strain. Fpn1 increased in C57BL/6 mice, but not in the DBA/2 ones in parenteral iron loading. Fpn1 protein did not change substantially in either condition. Hfe, Rgmc and Tfr2 expression was not influenced by phlebotomy. In parenteral iron overload, Tfr2 gene and protein expression decreased concomitant to the increase in Hepc, while Hfe RNA remained constant.Our results indicate that regulation of hepatic Fpn1 differs from that reported for duodenal Fpn1. Furthermore, taken the differences in gene expression in dietary overload (increased Hfe but not Tfr2), distinct roles are suggested for Hfe and Tfr2 in Hepc activation.

Published
2005

35. Long-term results of high-dose imatinib in children and adolescents with chronic myeloid leukaemia in chronic phase: the Italian experience

Author

Giona, F., Putti, M. C., Micalizzi, C., Menna, G., Moleti, M. L., Santoro, N., Iaria, G., Ladogana, S., Burnelli, R., Consarino, C., Varotto, S., Tucci, F., Messina, C., Nanni, M., Diverio, D., Biondi, A., Pession, A., Locatelli, Franco, Piciocchi, A., Gottardi, E., Saglio, G., Foa, R., Locatelli F. (ORCID:0000-0002-7976-3654), Giona, F., Putti, M. C., Micalizzi, C., Menna, G., Moleti, M. L., Santoro, N., Iaria, G., Ladogana, S., Burnelli, R., Consarino, C., Varotto, S., Tucci, F., Messina, C., Nanni, M., Diverio, D., Biondi, A., Pession, A., Locatelli, Franco, Piciocchi, A., Gottardi, E., Saglio, G., Foa, R., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Imatinib mesylate (IM) is used for the management of childhood chronic myeloid leukaemia (CML). The most effective dosage of IM and its long-term efficacy in children are not well defined. The purpose of this multicentre study is to report on the long-term results of high-dose IM (340 mg/m2/d) in CML patients in chronic phase (CP-CML) aged <18 years at diagnosis. A total of 47 CP-CML patients with a median age at diagnosis of 11 years 9 months were enrolled in nine Italian centres. Complete cytogenetic response was achieved in 91·5% of the evaluable patients at a median time of 6 months. BCR-ABL1 International Scale ≤ 0·1% (major molecular response; MMR) and ≤0·01% (molecular response; MR) at 12 months were 66·6% and 33%, respectively. During follow-up, MMR and MR were achieved in 78·6% and 61% of children, respectively. IM was safely discontinued in 3 long-term treated children with a durable MR. Twelve patients (eight cytogenetic/molecular responders) underwent stem cell transplantation. The progression-free survival probabilities at 96 months for responding patients who continued IM and for those transplanted were 60% and 50%, respectively. After a median follow-up of 52 months (range 3–146), all patients are alive. High-dose IM is a long-term effective therapy in children and adolescents with CP-CML.

Published
2015

36. Long-term results of high-dose imatinib in children and adolescents with chronic myeloid leukaemia in chronic phase: The Italian experience

Author

Giona, F, Putti, M, Micalizzi, C, Menna, G, Moleti, M, Santoro, N, Iaria, G, Ladogana, S, Burnelli, R, Consarino, C, Varotto, S, Tucci, F, Messina, C, Nanni, M, Diverio, D, Biondi, A, Pession, A, Locatelli, F, Piciocchi, A, Gottardi, E, Saglio, G, Foà, R, Foà, R., BIONDI, ANDREA, Giona, F, Putti, M, Micalizzi, C, Menna, G, Moleti, M, Santoro, N, Iaria, G, Ladogana, S, Burnelli, R, Consarino, C, Varotto, S, Tucci, F, Messina, C, Nanni, M, Diverio, D, Biondi, A, Pession, A, Locatelli, F, Piciocchi, A, Gottardi, E, Saglio, G, Foà, R, Foà, R., and BIONDI, ANDREA

Abstract

Imatinib mesylate (IM) is used for the management of childhood chronic myeloid leukaemia (CML). The most effective dosage of IM and its long-term efficacy in children are not well defined. The purpose of this multicentre study is to report on the long-term results of high-dose IM (340 mg/m2/d) in CML patients in chronic phase (CP-CML) aged <18 years at diagnosis. A total of 47 CP-CML patients with a median age at diagnosis of 11 years 9 months were enrolled in nine Italian centres. Complete cytogenetic response was achieved in 91·5% of the evaluable patients at a median time of 6 months. BCR-ABL1 International Scale ≤ 0·1% (major molecular response; MMR) and ≤0·01% (molecular response; MR) at 12 months were 66·6% and 33%, respectively. During follow-up, MMR and MR were achieved in 78·6% and 61% of children, respectively. IM was safely discontinued in 3 long-term treated children with a durable MR. Twelve patients (eight cytogenetic/molecular responders) underwent stem cell transplantation. The progression-free survival probabilities at 96 months for responding patients who continued IM and for those transplanted were 60% and 50%, respectively. After a median follow-up of 52 months (range 3–146), all patients are alive. High-dose IM is a long-term effective therapy in children and adolescents with CP-CML.

Published
2015

37. Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia.

Author

Cross, N C P, White, H E, Colomer, D, Ehrencrona, Hans, Foroni, L, Gottardi, E, Lange, T, Lion, T, Machova Polakova, K, Dulucq, S, Martinelli, G, Oppliger Leibundgut, E, Pallisgaard, N, Barbany, G, Sacha, T, Talmaci, R, Izzo, B, Saglio, G, Pane, F, Müller, M C, Hochhaus, A, Cross, N C P, White, H E, Colomer, D, Ehrencrona, Hans, Foroni, L, Gottardi, E, Lange, T, Lion, T, Machova Polakova, K, Dulucq, S, Martinelli, G, Oppliger Leibundgut, E, Pallisgaard, N, Barbany, G, Sacha, T, Talmaci, R, Izzo, B, Saglio, G, Pane, F, Müller, M C, and Hochhaus, A

Abstract

Treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors has advanced to a stage where many patients achieve very low or undetectable levels of disease. Remarkably, some of these patients remain in sustained remission when treatment is withdrawn, suggesting that they may be at least operationally cured of their disease. Accurate definition of deep molecular responses (MRs) is therefore increasingly important for optimal patient management and comparison of independent data sets. We previously published proposals for broad standardized definitions of MR at different levels of sensitivity. Here we present detailed laboratory recommendations, developed as part of the European Treatment and Outcome Study for CML (EUTOS), to enable testing laboratories to score MR in a reproducible manner for CML patients expressing the most common BCR-ABL1 variants.Leukemia advance online publication, 27 February 2015; doi:10.1038/leu.2015.29.

Published
2015

38. Molecular monitoring of acute myeloid leukemia associated with inv(16): Threshold of CBFβ/MYH11 transcript copy number above which relapse occurs and below which continuous complete remission is likely (multiple letters) [8]

Author

Martinelli G., Buonamici S., Visani G., Malagola M., Piccaluga P. P., Isidori A., Bosi C., Bonifazi F., Soverini S., Terragna C., Amabile M., Giannini B., Baccarani M., Guerrasio A., Pilatrino C., Cilloni D., Gottardi E., Saglio G., Martinelli G., Buonamici S., Visani G., Malagola M., Piccaluga P.P., Isidori A., Bosi C., Bonifazi F., Soverini S., Terragna C., Amabile M., Giannini B., Baccarani M., Guerrasio A., Pilatrino C., Cilloni D., Gottardi E., and Saglio G.

Subjects
inv(16) CBFβ/MYH11 Acute myeloid leukemia PCR
Abstract

na

Published
2003

40. Measurement of low temperature specific heat of crystalline TeO2 for the optimization of bolometric detectors

Author

Barucci, M, Brofferio, C, Giuliani, ANDREA ERNESTO GUIDO, Gottardi, E, Peroni, I, Ventura, G., Barucci, M, Brofferio, C, Giuliani, A, Gottardi, E, Peroni, I, and Ventura, G

Subjects
FIS/01 - FISICA SPERIMENTALE, Debye temperature, specific heat, bolometers, low temperatures, TeO2, FIS/03 - FISICA DELLA MATERIA
Abstract

The optimization of bolometric detectors, like those that will be developed for the rare event experiment CUORE, requires a complete knowledge of the detector's thermal parameters. Since the CUORE detecting elements will consist of TeO2 crystals, we have measured the specific heat of this material down to 60 mK with the thermal relaxation method. Previous available data were taken at temperatures higher than 0.6K, Our results al e clear ly consistent with a lattice dominated specific heat. The Debye temperature, evaluated to be (232 +/- 7), is in excellent agreement with the elastic constant values measured by other authors. The knowledge of the Debye temperature allows a simple prediction of the pulse amplitude of presently working bolometers.

Published
2001

42. Efficacia dell’imatinib in bambini ed adolescenti con leucemia mieloide cronica philadelphia positiva trattati in fase cronica. [Imatinib effective in children and adolescents with Ph+ chronic myeloid leukemia treated in chronic phase]

Author

Giona, Fiorina, Putti, M. C., Santoro, N., Gottardi, E., Ladogana, S., Micalizzi, C., Iaria, C., Consarrino, C., Burnelli, R., Rea, M., Moleti, M. L., Testi, Anna Maria, Cavillo, M., Cecinati, V., Nanni, M., Messina, C., Diverio, D., Varotto, S., Biondi, A., Pession, A., Saglio, G., and Foà, R.

Published
2010

44. ITALIAN STANDARDIZATION OF BCR-ABL RQ-PCR AND QUALITY CONTROL METHODS: AN OVERVIEW OF FIRST 4 YEARS RESULTS

Author

Izzo, B, Quarantelli, F, Muccioli Casadei, G, Farina, V, Amabile, M, Gottardi, E, Minervini, A, Spinelli, O, Stella, S, Scappini, B, Garuti, A, Pezzetti, L, Colnaghi, F, Monne, M, Santoro, A, Rocca, B, Di Ianni, M, Giannini, B, Diverio, D, Zaza, S, De Matteis, G, Ruggeri, G, Minervini, M, Galimberti, Sara, Coluzzi, S, Novella, E, Berardinelli, E, Saglio, G, Martinelli, G, and Pane, F.

Published
2010

46. ACCURACY AND PRECISION OF RESULTS AFTER IMPLEMENTATION OF INTERNATIONAL SCALE TO EVALUATE MINIMAL RESIDUAL DISEASE IN CHRONIC MYELOID LEUKEMIA PATIENTS COORDINATED ON BEHALF OF GIMEMA-CML WP

Author

Quarantelli, F, Izzo, B, Amabile, M, Gottardi, E, Albano, F, Spinelli, O, Vigneri, P, Gozzini, A, Garuti, A, Pezzetti, L, Colnaghi, F, Monne, M, Santoro, A, Bernasconi, P, Di Ianni, M, Donati, M, Giannini, B, Mammi’, C, Diverio, D, Divona, M. D., De Matteis, G, Rossi, G, Culurgioni, F, Minervini, M, Galimberti, Sara, Nicci, C, Saglio, G, Martinelli, G, and Pane, F.

Published
2009

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