Haematologica (Feb 2019)
Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia
- Panagiotis Baliakas,
- Theodoros Moysiadis,
- Anastasia Hadzidimitriou,
- Aliki Xochelli,
- Sabine Jeromin,
- Andreas Agathangelidis,
- Mattias Mattsson,
- Lesley-Ann Sutton,
- Eva Minga,
- Lydia Scarfò,
- Davide Rossi,
- Zadie Davis,
- Neus Villamor,
- Helen Parker,
- Jana Kotaskova,
- Evangelia Stalika,
- Karla Plevova,
- Larry Mansouri,
- Diego Cortese,
- Alba Navarro,
- Julio Delgado,
- Marta Larrayoz,
- Emma Young,
- Achilles Anagnostopoulos,
- Karin E. Smedby,
- Gunnar Juliusson,
- Oonagh Sheehy,
- Mark Catherwood,
- Jonathan C. Strefford,
- Niki Stavroyianni,
- Chrysoula Belessi,
- Sarka Pospisilova,
- David Oscier,
- Gianluca Gaidano,
- Elias Campo,
- Claudia Haferlach,
- Paolo Ghia,
- Richard Rosenquist,
- Kostas Stamatopoulos
Affiliations
- Panagiotis Baliakas
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden
- Theodoros Moysiadis
- Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece
- Anastasia Hadzidimitriou
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden;Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece
- Aliki Xochelli
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden;Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece
- Sabine Jeromin
- MLL Munich Leukemia Laboratory, Munich, Germany
- Andreas Agathangelidis
- Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece
- Mattias Mattsson
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden
- Lesley-Ann Sutton
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden
- Eva Minga
- Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece
- Lydia Scarfò
- Division of Experimental Oncology, IRCCS Istituto Scientifico San Raffaele and Università Vita-Salute San Raffaele, Milan, Italy
- Davide Rossi
- Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
- Zadie Davis
- Department of Haematology, Royal Bournemouth Hospital, UK
- Neus Villamor
- Hemopathology Unit, Hospital Clinic, Barcelona, Spain
- Helen Parker
- Cancer Genomics, Academic Unit of Cancer Sciences, Cancer Research UK Centre and Experimental Cancer Medicine Centre, Faculty of Medicine, University of Southampton, UK
- Jana Kotaskova
- Central European Institute of Technology, Masaryk University and University Hospital Brno, Czech Republic
- Evangelia Stalika
- Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece;Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece
- Karla Plevova
- Central European Institute of Technology, Masaryk University and University Hospital Brno, Czech Republic
- Larry Mansouri
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden
- Diego Cortese
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden
- Alba Navarro
- Hemopathology Unit, Hospital Clinic, Barcelona, Spain
- Julio Delgado
- Hematology Department, Hospital Clinic, Barcelona, Spain
- Marta Larrayoz
- Cancer Genomics, Academic Unit of Cancer Sciences, Cancer Research UK Centre and Experimental Cancer Medicine Centre, Faculty of Medicine, University of Southampton, UK
- Emma Young
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden
- Achilles Anagnostopoulos
- Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece
- Karin E. Smedby
- Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden
- Gunnar Juliusson
- Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Sweden
- Oonagh Sheehy
- Department of Hemato-Oncology, Belfast City Hospital, UK
- Mark Catherwood
- Department of Hemato-Oncology, Belfast City Hospital, UK
- Jonathan C. Strefford
- Cancer Genomics, Academic Unit of Cancer Sciences, Cancer Research UK Centre and Experimental Cancer Medicine Centre, Faculty of Medicine, University of Southampton, UK
- Niki Stavroyianni
- Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece
- Chrysoula Belessi
- Hematology Department, Nikea General Hospital, Pireaus, Greece
- Sarka Pospisilova
- Central European Institute of Technology, Masaryk University and University Hospital Brno, Czech Republic
- David Oscier
- Department of Haematology, Royal Bournemouth Hospital, UK
- Gianluca Gaidano
- Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy
- Elias Campo
- Hemopathology Unit, Hospital Clinic, Barcelona, Spain;Department of Pathology, University of Barcelona, Spain
- Claudia Haferlach
- MLL Munich Leukemia Laboratory, Munich, Germany
- Paolo Ghia
- Division of Experimental Oncology, IRCCS Istituto Scientifico San Raffaele and Università Vita-Salute San Raffaele, Milan, Italy
- Richard Rosenquist
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Kostas Stamatopoulos
- Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden;Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece
- DOI
- https://doi.org/10.3324/haematol.2018.195032
- Journal volume & issue
-
Vol. 104,
no. 2
Abstract
Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to-first-treatment and a treatment probability at five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet A U-CLL patients, besides TP53 abnormalities, del(11q) and/or SF3B1 mutations were associated with the shortest time-to-first-treatment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage CLL patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in CLL.
