Chronic myelogenous leukemia

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

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 associated with 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.

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Acknowledgements

The cooperation, the advices and the comments of the members of the International Childhood CML Registry, the GIMEMA CML Working Party, the French, German, and Taiwan CML Study Groups, the Arab LeukemiaNet, and of Mohammed Azzazi, Susan Branford, Richard Clark, Nicholas Cross, Letizia Foroni, Torsten Haferlach, Quian Jiang, Eric Lippert, Junia Melo, and Dietger Niederwieser, are kindly acknowledged. The skilled technical support of Michela Apolinari and Chiara Ferri is kindly acknowledged. This work was supported in part by the ELN Foundation.

The members of the International BCR-ABL1 Study Group

AFRICA: Algeria: Mohamed-Amine Bekadja, Badra Entasoltan, Mourad Nachi, EHU 1er Novembre, Oran; Egypt: Ashraf Elghandour, Manal El Sorady, Alexandria University, Alexandria; Raafat Abdelfattah, Yasser El Nahass, Mohamed Samra, NCI, Cairo; Mohammed Azzazi, Ezat Elsobki, Mohamed Moussa, Ain Shams University, Cairo; Omar Fahmy, Mervat Mattar, Cairo University, Cairo; Samir Eid Shehata, Asuit University, Cairo; Emad Azmy, Mansoura University and Cancer Center, Mansoura; Nigeria: Rahman A. Bolarinwa, Obafemi Awolowo University, Ile-Ife; Tunisia: Samir Eid, Abderrhaim Khelif, Farhat Hached, Teaching Hospital, Sousse; Samia Menif, Pasteur Institute, Tunis. ASIA: Bangladesh: Hafizur Rahman, International Center for Diarrhoeal Disease, Dhaka; China: Xiaojun Huang, Qian Jiang, Peking University People's Hospital and Peking University Inst. of Hematology, Bejin; Yuanxin Ye, Huanling Zhu, West China Hospital, Sichuan University, Sichuan; Suning Chen, The First Affiliated Hospital of Soochow University, Suzhou; India: Neelam Varma, PGIMER, Chandigarh; Prasanth Ganesan, Cancer Inst. (WIA), Chennai; Sadashivudu Gundeti, Nizam's Inst. of Medical Sciences, Hyderabad; Hemant Malhotra, RK Birla Cancer Center, Jaipur; Vivek S. Radhakrishnan, Tata Medical Center, Kolkata; Lalit Kumar, Surender Kumar Sharawat, All India Inst. of Medical Science, New Delhi; Tulika Seth, AIIMS, New Delhi; B.V. Ausekar, Shiddheshwar Cancer Hospital and Research Center, Solapur; Poonkuzhali Balasubramanian, Christian Medical College, Vellore; Iran: Behzad Poopak, Islamic Azada University and Payvand Clinical and Specialty Laboratory, Tehran; Japan: Koiti Inokuchi, Nippon Medical School, Tokyo; Korea S.: Dong-Wook Kim, Seoul St. Mary's Hospital, Leukemia Research Unit, The Catholic University of Korea, Seoul; Oman: Salam Al Kindi, Sultan Qaboos University, Muscat; Philippines: Angelina Mirasol, The Philippines General Hospital, Manila; Saudi Arabia: Mohammed Qari, King Abdul Aziz University Hospital, Jeddah; Singapore: Yeow Tee Goh, Singapore General Hospital, Singapore; Taiwan: Lee-Yung Shih, Chang Gung University and Chang Gung Memorial Hospital, Linkou. AUSTRALIA: Susan Branford, University of Adelaide and University of South Australia, Adelaide. EUROPE: Austria: Thomas Lion, Children’s Cancer Research Institute, Vienna; Peter Valent, Medical University of Vienna, Vienna; Sonja Burgstaller, Joseph Thaler, Klinikum Wels-Grieskirchen, Wels; Croatia: Boris Labar, Renata Zadro, University Hospital Center Zagreb, Zagreb; Czech Republic: Jiri Mayer, Daniela Zackova, University Hospital Brno and Masaryk University, Brno; Edgar Faber, Palacky University, Olomouc; Denmark: Niels Pallisgaard, Sjaellands Universitethospital, Roskilde; France: François Xavier-Mahon, University of Bordeaux, Bordeaux; Eric Lippert, CHU, Brest; Jean Michel Cayuela, Delphine Réa, Hopital Saint Louis, Paris; Frederic Millot; CHU de Poitiers,Poitiers; Germany: Meinolf Suttorp, Universitaetsklinikum Carl Gustav Carus, Dresden; Andreas Hochhaus, Universitaetsklinikum Jena, Jena; Dietger Niederwieser, University of Leipzig, Leipzig; Susanne Saussele, University Clinic Mannheim, Mannheim; Torsten Haferlach, Sabine Jeromine, MLL Muenchner Leukaemielabor, Muenchen; Greece: Panayiotis Panayiotidis, University of Athens and Laikon General Hospital, Athens; Ireland: Eibhlin Conneally, Steve Langabeer, St. James Hospital, Dublin; Israel: Arnon Nagler, Chaim Sheba Medical Center and Tel Aviv University, Tel Aviv; Italy: Serena Rupoli, University of Ancona, Ancona; Nicola Santoro, Azienda Ospedaliero-Universitaria "Policlinico Consorziale", Bari; Francesco Albano, University of Bari, Bari; Fausto Castagnetti, Emanuela Ottaviani, University of Bologna and S.Orsola-Malpighi University Hospital, Bologna; Alessandro Rambaldi, University of Milano and AAST Papa Giovanni XXIII, Bergamo; Fabio Stagno, University of Catania, Catania; Stefano Molica, A. Ospedale Pugliese Ciaccio, Catanzaro; Caterina Biagiotti, Barbara Scappini, University of Florence, Florence; Roberto Lemoli, University of Genova, Genova; Alessandra Iurlo, Fondazione IRCCS Ca' Granda and University of Milano, Milano; Ester Pungolino, Ospedale Niguarda, Milano; Giuseppe Menna, Fara Petruzziello, Ospedale Pausillipon, Napoli; Fabrizio Pane, University Federico II, Napoli; Enrico Gottardi, Giovanna Rege-Cambrin, S. Luigi Gonzaga Hospital and University of Torino, Orbassano; Gianni Binotto, University of Padova, Padova; Maria Caterina Putti, Clinica di Emato-oncologia Pediatrica, Azienda Ospedaliera, Padova; Franca Falzetti, University of Perugia, Perugia; Giuseppe Visani, Ospedale S.Salvatore, Pesaro; Sara Galimberti, University of Pisa, Pisa; Pellegrino Musto, IRCCS-CROB, Rionero in Vulture; Elisabetta Abruzzese, S. Eugenio Hospital, Roma; Massimo Breccia, Fiorina Giona, Sapienza University, Roma; Patrizia Chiusolo, Simona Sica, Policlinico Gemelli, Roma; Carmen Fava, Dario Ferrero, University of Torino, Torino; Mario Tiribelli, University of Udine, Udine; Massimiliano Bonifacio, University of Verona, Verona; Lithuania: Laimonas Griskevicius, Vilnius University, Vilnius; Moldova: Vasile Musteata, State University of Medicine and Pharmacy “N. Testemitanu”, Chisinau; Netherlands: Jeroen Janssen, VU University Medical Center, Amsterdam; Poland: Witold Prejzner, Medical University of Gdansk, Gdansk; Tomasz Sacha, Joanna Waclaw, Jagiellonian University Hospital, Krakow; Portugal: Antonio Medina Almeida, Inst. Portugues de Oncologia de Lisboa Francisco Gentil, Lisboa; Russia: Sergei Kulikov, Anna Turkina, National Research Center for Hematology of Ministry for Healthcare of Russian Federation, Moscow; Serbia: Andrjia Bogdanovic, Clinical Center of Serbia, University of Belgrade, Belgrade; Slovenia: Irena Zupan, University Clinical Center, Ljubljana; Spain: Silvia Marcé, Hospital Germans Trias i Pujol-ICO Badalona, Badalona; Francisco Cervantes, Hospital Clinic Barcelona, IDIBAPS, Barcelona; Juan Luis Steegmann, Hospital Universitario de la Princesa, Madrid; Ukraine: Konstyantyn Kotlyarchuk, SI Inst. of Blood Pathology and Transfusion Medicine, Lviv; United Kingdom: Benedict J. Milner, Aberdeen Royal Infirmary, Aberdeen; Susan Rose, Birmingham Women’s NHS Foundation Trust, Birmingham; Tim Clench, Bristol Royal Infirmary, Bristol; Paula Waits, Bristol Genetics Laboratory, Bristol; Steve Austin, Cardiff and Vale University Health Board, Cardiff; Caroline Wickham, Royal Devon and Exeter NHS Foundation Trust, Exeter; Richard Clark, Royal Liverpool University Hospital, Liverpool; Jane Apperley, Simone Claudiani, Letizia Foroni, Richard Szydlo, Imperial College London, Hammersmith Hospital, London; Emma Burt, The Royal London Hospital, London; Ruth Bescoby, Leanne Cork, Stephen O'Brien, University of Newcastle, Newcastle; Bethaney Green, Sarah Hawtree, Mark Watson, Sheffield Diagnostics Genetics Services, Sheffield. SOUTH AMERICA: Argentina: Raquel Maria Bengiò, Irene Larripa, IIHEMA-Academia Nacional de Medicina, Buenos Aires; Carolina Pavlovsky, FUNDALEU, Hospitalization and Clinical Research Center, Buenos Aires; Beatriz Moiraghi, Hospital JM Ramos Mejia, CABA, Buenos Aires; Brasil: Cristiane Almeida Requiao de Pinna, Federal University Hospital of Bahia, Bahia; Gustavo Henrique Romani Magalhaes, Minas Gerais Federal University-Hospital das Clinicas, Belo Horizonte; Katia Pagnano, University of Campinas, Campinas; Vaneuza Funke, Federal University of Parana, Curitiba; Renato Sampaio Tavares, Hospital das Clinicas da UFG, Goiania; Adriana Prado, Clinical Hospital of Federal University of Goias, Goias; Alita Andrade Azevedo, Centro de Hematologia e Hematoterapia de Pernambuco, Pernambuco; Laura Fogliatto, Hospital de Clinicas de Porto Alegre, Porto Alegre; Simone Bonecker, CEMO/INCA, Rio de Janeiro; Renato Centrone, Inst. Hemomed of Oncology and Hematology, Rio de Janeiro; Artur Moellman, INCA/MS, Rio de Janeiro; Israel Bendit, University of Sao Paulo, Sao Paulo; Monika Conchon, Hospital Santa Marcelina, Sao Paulo; Paraguay: Maria Elida Centurion, Central Hospital of Asuncion, Asuncion; Uruguay: Ana-Ines Prado, Hospital Maciel, Montevideo; Venezuela: JL Lopez, Banco Municipal de Sangre del DC, Caracas.

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Correspondence to Michele Baccarani.

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The members of the International BCR-ABL1 Study Group are listed before the references in alphabetical order, by continent, by country, by town, and by name

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Baccarani, M., Castagnetti, F., Gugliotta, G. et al. The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview. Leukemia 33, 1173–1183 (2019). https://doi.org/10.1038/s41375-018-0341-4

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