Comprehensive analysis of isolated der(1;7)(q10;p10) in a large international homogenous cohort of patients with myelodysplastic syndromes
Corresponding Author
Christina Ganster
Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany
Correspondence
Christina Ganster, Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany.
Email: [email protected]
Search for more papers by this authorCatharina Müller-Thomas
Department of Hematology and Medical Oncology III, Technische Universität München, Munich, Germany
Search for more papers by this authorClaudia Haferlach
MLL Munich Leukemia Laboratory, Munich, Germany
Search for more papers by this authorCorinna Strupp
Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-Universität, Düsseldorf, Germany
Search for more papers by this authorKiyoyuki Ogata
Metropolitan Research and Treatment Center for Blood Disorders (MRTC Japan), Tokyo, Japan
Search for more papers by this authorUlrich Germing
Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-Universität, Düsseldorf, Germany
Search for more papers by this authorBarbara Hildebrandt
Institute of Human Genetics and Anthropology, Heinrich-Heine-Universität, Düsseldorf, Germany
Search for more papers by this authorMar Mallo
Josep Carreras Leukemia Research Institute (IJC), ICO-Hospital GermansTrias i Pujol, Universitat Autonòma de Barcelona, Barcelona, Spain
Search for more papers by this authorMichael Lübbert
Division of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg, Freiburg, Germany
Search for more papers by this authorChristel Müller
Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, Leipzig University Hospital, Leipzig, Germany
Search for more papers by this authorFrancesc Solé
Josep Carreras Leukemia Research Institute (IJC), ICO-Hospital GermansTrias i Pujol, Universitat Autonòma de Barcelona, Barcelona, Spain
Search for more papers by this authorKatharina S. Götze
Department of Hematology and Medical Oncology III, Technische Universität München, Munich, Germany
Search for more papers by this authorPeter Vandenberghe
Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium
Search for more papers by this authorGudrun Göhring
Department of Human Genetics, Hannover Medical School, Hannover, Germany
Search for more papers by this authorTilman Steinmetz
Onkologie Köln, Outpatient Clinic for Hematology and Oncology, Köln, Germany
Search for more papers by this authorNicolaus Kröger
Department of Stem Cell Transplantation, University of Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorUwe Platzbecker
Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, Leipzig University Hospital, Leipzig, Germany
Search for more papers by this authorUlrike Söling
Outpatient Clinic for Hematology and Oncology, Kassel, Germany
Search for more papers by this authorSophie Raynaud
Département d'hématologie biologique, Hôpital Pasteur, Nice, France
Search for more papers by this authorKatayoon Shirneshan
Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany
Search for more papers by this authorJulie Schanz
Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany
Search for more papers by this authorDetlef Haase
Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany
Search for more papers by this authorCorresponding Author
Christina Ganster
Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany
Correspondence
Christina Ganster, Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany.
Email: [email protected]
Search for more papers by this authorCatharina Müller-Thomas
Department of Hematology and Medical Oncology III, Technische Universität München, Munich, Germany
Search for more papers by this authorClaudia Haferlach
MLL Munich Leukemia Laboratory, Munich, Germany
Search for more papers by this authorCorinna Strupp
Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-Universität, Düsseldorf, Germany
Search for more papers by this authorKiyoyuki Ogata
Metropolitan Research and Treatment Center for Blood Disorders (MRTC Japan), Tokyo, Japan
Search for more papers by this authorUlrich Germing
Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-Universität, Düsseldorf, Germany
Search for more papers by this authorBarbara Hildebrandt
Institute of Human Genetics and Anthropology, Heinrich-Heine-Universität, Düsseldorf, Germany
Search for more papers by this authorMar Mallo
Josep Carreras Leukemia Research Institute (IJC), ICO-Hospital GermansTrias i Pujol, Universitat Autonòma de Barcelona, Barcelona, Spain
Search for more papers by this authorMichael Lübbert
Division of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg, Freiburg, Germany
Search for more papers by this authorChristel Müller
Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, Leipzig University Hospital, Leipzig, Germany
Search for more papers by this authorFrancesc Solé
Josep Carreras Leukemia Research Institute (IJC), ICO-Hospital GermansTrias i Pujol, Universitat Autonòma de Barcelona, Barcelona, Spain
Search for more papers by this authorKatharina S. Götze
Department of Hematology and Medical Oncology III, Technische Universität München, Munich, Germany
Search for more papers by this authorPeter Vandenberghe
Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium
Search for more papers by this authorGudrun Göhring
Department of Human Genetics, Hannover Medical School, Hannover, Germany
Search for more papers by this authorTilman Steinmetz
Onkologie Köln, Outpatient Clinic for Hematology and Oncology, Köln, Germany
Search for more papers by this authorNicolaus Kröger
Department of Stem Cell Transplantation, University of Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorUwe Platzbecker
Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, Leipzig University Hospital, Leipzig, Germany
Search for more papers by this authorUlrike Söling
Outpatient Clinic for Hematology and Oncology, Kassel, Germany
Search for more papers by this authorSophie Raynaud
Département d'hématologie biologique, Hôpital Pasteur, Nice, France
Search for more papers by this authorKatayoon Shirneshan
Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany
Search for more papers by this authorJulie Schanz
Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany
Search for more papers by this authorDetlef Haase
Clinics of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany
Search for more papers by this authorFunding information Generalitat de Catalunya, Grant/Award Number: 2017 SGR288 (GRC); Instituto de Salud Carlos III, Ministerio de Economia y Competividad, Spain, Grant/Award Numbers: PI/14/00013, PI/17/0575; Fundació Internacional Josep Carreras; “la Caixa” Foundation; CERCA Programme/Generalitat de Catalunya; Celgene Spain
Abstract
The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the new comprehensive cytogenetic scoring system for MDS, chromosome 7 anomalies are no longer generally assigned to poor risk features but are thoroughly separated. However, der(1;7)(q10;p10), hereinafter der(1;7), is merged into the group labeled “any other single” and belongs to the intermediate risk group, just by definition due to lack of adequate clinical data. The aim of our international collaborative was to clarify the “real” prognostic impact of der(1;7) on a homogenous and well-documented data base. We performed detailed analysis of 63 MDS patients with isolated der(1;7) constituting the largest cohort hitherto reported. Furthermore, clinical data are compared with those of patients with isolated del(7q) and isolated monosomy 7. Median overall survival (OS) of patients with der(1;7) is 26 months (hazard ratio (HR) 0.91 for del(7q) vs der(1;7) and 2.53 for monosomy 7 vs der(1;7)). The der(1;7) is associated with profound thrombocytopenia most probably causing the reduced OS which is in striking contrast to the low risk for AML transformation (HR 3.89 for del(7q) vs der(1;7) and 5.88 for monosomy 7 vs der(1;7)). Molecular karyotyping indicates that der(1;7) is generated in a single step during mitosis and that a chromosomal imbalance rather than a single disrupted gene accounts for malignancy. Thus, the current cytogenetic scoring system assigning isolated der(1;7) to the intermediate risk group is now confirmed by a sufficient data set.
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