Comprehensive sequential genetic analysis delineating frequency, patterns, and prognostic impact of genomic dynamics in a real‐world cohort of patients with lower‐risk MDS
Paolo Mazzeo,
Christina Ganster,
John Wiedenhöft,
Katayoon Shirneshan,
Katharina Rittscher,
Elzbieta B. Brzuszkiewicz,
Doris Steinemann,
Maximilian Schieck,
Catharina Müller‐Thomas,
Hannes Treiber,
Friederike Braulke,
Ulrich Germing,
Katja Sockel,
Ekaterina Balaian,
Julie Schanz,
Uwe Platzbecker,
Katharina S. Götze,
Detlef Haase
Affiliations
Paolo Mazzeo
Department of Hematology and Medical Oncology, INDIGHO laboratory University Medical Center Göttingen (UMG) Göttingen Germany
Christina Ganster
Department of Hematology and Medical Oncology, INDIGHO laboratory University Medical Center Göttingen (UMG) Göttingen Germany
John Wiedenhöft
Department of Human Genetics University of Leipzig Medical Center Leipzig Germany
Katayoon Shirneshan
Department of Hematology and Medical Oncology, INDIGHO laboratory University Medical Center Göttingen (UMG) Göttingen Germany
Katharina Rittscher
Department of Hematology and Medical Oncology, INDIGHO laboratory University Medical Center Göttingen (UMG) Göttingen Germany
Elzbieta B. Brzuszkiewicz
Department of Hematology and Medical Oncology, INDIGHO laboratory University Medical Center Göttingen (UMG) Göttingen Germany
Doris Steinemann
Department of Human Genetics Hannover Medical School Hannover Germany
Maximilian Schieck
Department of Human Genetics Hannover Medical School Hannover Germany
Catharina Müller‐Thomas
Department of Medicine III Technical University of Munich School of Medicine and Health Munich Germany
Hannes Treiber
Department of Hematology and Medical Oncology, INDIGHO laboratory University Medical Center Göttingen (UMG) Göttingen Germany
Friederike Braulke
Department of Hematology and Medical Oncology, INDIGHO laboratory University Medical Center Göttingen (UMG) Göttingen Germany
Ulrich Germing
Department of Hematology, Oncology and Clinical Immunology Heinrich‐Heine‐Universität Düsseldorf Germany
Katja Sockel
Medical Clinic and Policlinic I University Hospital Carl Gustav Carus Dresden Dresden Germany
Ekaterina Balaian
Medical Clinic and Policlinic I University Hospital Carl Gustav Carus Dresden Dresden Germany
Julie Schanz
Department of Hematology and Medical Oncology, INDIGHO laboratory University Medical Center Göttingen (UMG) Göttingen Germany
Uwe Platzbecker
Medical Clinic and Policlinic 1, Hematology and Cellular Therapy Leipzig University Hospital Leipzig Germany
Katharina S. Götze
Department of Medicine III Technical University of Munich School of Medicine and Health Munich Germany
Detlef Haase
Department of Hematology and Medical Oncology, INDIGHO laboratory University Medical Center Göttingen (UMG) Göttingen Germany
Abstract The acquisition of subsequent genetic lesions (clonal evolution, CE) and/or the expansion of existing clones (CEXP) contributes to clonal dynamics (CD) in myelodysplastic syndromes (MDS). Although CD plays an important role in high‐risk patients in disease progression and transformation into acute myeloid leukemia (AML), knowledge about CD in lower‐risk MDS (LR‐MDS) patients is limited due to lack of robust longitudinal data considering the long clinically stable courses of the disease. In this retrospective analysis, we delineate the frequency and the prognostic impact of CD in an unselected real‐world cohort of LR‐MDS patients. We screened 68 patients with a median follow‐up of 40.5 months and a median of 7.5 (range: 2–22) timepoints for CE and CEXP detected by chromosomal banding analysis, fluorescence in situ hybridization, sequencing, and molecular karyotyping. In 30/68 patients, 47 CE events and a CD rate of 1 event per 4 years were documented. Of note, patients with at least 1 CE event had an increased probability for subsequent treatment. Unexpectedly, CE did not correlate with inferior outcomes, which could be reasonably explained by CD detection triggering the subsequent start of a disease‐modifying therapy.