Haematologica (Aug 2016)
Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors
- Lesley-Ann Sutton,
- Emma Young,
- Panagiotis Baliakas,
- Anastasia Hadzidimitriou,
- Theodoros Moysiadis,
- Karla Plevova,
- Davide Rossi,
- Jana Kminkova,
- Evangelia Stalika,
- Lone Bredo Pedersen,
- Jitka Malcikova,
- Andreas Agathangelidis,
- Zadie Davis,
- Larry Mansouri,
- Lydia Scarfò,
- Myriam Boudjoghra,
- Alba Navarro,
- Alice F. Muggen,
- Xiao-Jie Yan,
- Florence Nguyen-Khac,
- Marta Larrayoz,
- Panagiotis Panagiotidis,
- Nicholas Chiorazzi,
- Carsten Utoft Niemann,
- Chrysoula Belessi,
- Elias Campo,
- Jonathan C. Strefford,
- Anton W. Langerak,
- David Oscier,
- Gianluca Gaidano,
- Sarka Pospisilova,
- Frederic Davi,
- Paolo Ghia,
- Kostas Stamatopoulos,
- Richard Rosenquist
Affiliations
- Lesley-Ann Sutton
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
- Emma Young
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
- Panagiotis Baliakas
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
- Anastasia Hadzidimitriou
- Institute of Applied Biosciences, CERTH, Thessaloniki, Greece
- Theodoros Moysiadis
- Institute of Applied Biosciences, CERTH, Thessaloniki, Greece
- Karla Plevova
- Central European Institute of Technology, Masaryk University and University Hospital Brno, Czech Republic
- Davide Rossi
- Division of Haematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy
- Jana Kminkova
- Central European Institute of Technology, Masaryk University and University Hospital Brno, Czech Republic
- Evangelia Stalika
- Institute of Applied Biosciences, CERTH, Thessaloniki, Greece
- Lone Bredo Pedersen
- Department of Hematology, Rigshospitalet, Copenhagen, Denmark
- Jitka Malcikova
- Central European Institute of Technology, Masaryk University and University Hospital Brno, Czech Republic
- Andreas Agathangelidis
- Università Vita-Salute San Raffaele, Milan, Italy;Division of Experimental Oncology and Department of Onco-Hematology, IRCCS, San Raffaele Scientific Institute, Milan, Italy
- Zadie Davis
- Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK
- Larry Mansouri
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
- Lydia Scarfò
- Università Vita-Salute San Raffaele, Milan, Italy;Division of Experimental Oncology and Department of Onco-Hematology, IRCCS, San Raffaele Scientific Institute, Milan, Italy
- Myriam Boudjoghra
- Hematology Department and University Pierre et Marie Curie, Hopital Pitie-Salpetriere, Paris, France
- Alba Navarro
- Hematopathology Unit and Department of Hematology, Hospital Clinic, University of Barcelona, Institut d’Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Barcelona, Spain
- Alice F. Muggen
- Department of Immunology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
- Xiao-Jie Yan
- The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York, NY, USA
- Florence Nguyen-Khac
- Hematology Department and University Pierre et Marie Curie, Hopital Pitie-Salpetriere, Paris, France
- Marta Larrayoz
- Cancer Sciences, Faculty of Medicine, University of Southampton, UK
- Panagiotis Panagiotidis
- First Department of Propaedeutic Medicine, University of Athens, Greece
- Nicholas Chiorazzi
- The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York, NY, USA
- Carsten Utoft Niemann
- Department of Hematology, Rigshospitalet, Copenhagen, Denmark
- Chrysoula Belessi
- Hematology Department, Nikea General Hospital, Piraeus, Greece
- Elias Campo
- Hematopathology Unit and Department of Hematology, Hospital Clinic, University of Barcelona, Institut d’Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Barcelona, Spain
- Jonathan C. Strefford
- Cancer Sciences, Faculty of Medicine, University of Southampton, UK
- Anton W. Langerak
- Department of Immunology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
- David Oscier
- Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK
- Gianluca Gaidano
- Division of Haematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy
- Sarka Pospisilova
- Central European Institute of Technology, Masaryk University and University Hospital Brno, Czech Republic
- Frederic Davi
- Hematology Department and University Pierre et Marie Curie, Hopital Pitie-Salpetriere, Paris, France
- Paolo Ghia
- Università Vita-Salute San Raffaele, Milan, Italy;Division of Experimental Oncology and Department of Onco-Hematology, IRCCS, San Raffaele Scientific Institute, Milan, Italy
- Kostas Stamatopoulos
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden;Institute of Applied Biosciences, CERTH, Thessaloniki, Greece;Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece
- Richard Rosenquist
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
- DOI
- https://doi.org/10.3324/haematol.2016.141812
- Journal volume & issue
-
Vol. 101,
no. 8
Abstract
We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (BIRC3, MYD88, NOTCH1, SF3B1 and TP53) and cytogenetic aberrations, we reveal a subset-biased acquisition of gene mutations. More specifically, the frequency of NOTCH1 mutations was found to be enriched in subsets expressing unmutated immunoglobulin genes, i.e. #1, #6, #8 and #59 (22–34%), often in association with trisomy 12, and was significantly different (P
