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Genome-wide DNA methylation analysis pre- and post-lenalidomide treatment in patients with myelodysplastic syndrome with isolated deletion (5q).
Hecht, Anna; Meyer, Julia A; Jann, Johann-Christoph; Sockel, Katja; Giagounidis, Aristoteles; Götze, Katharina S; Letsch, Anne; Haase, Detlef; Schlenk, Richard F; Haferlach, Torsten; Schafhausen, Philippe; Bug, Gesine; Lübbert, Michael; Thol, Felicitas; Büsche, Guntram; Schuler, Esther; Nowak, Verena; Obländer, Julia; Fey, Stephanie; Müller, Nadine; Metzgeroth, Georgia; Hofmann, Wolf-Karsten; Germing, Ulrich; Nolte, Florian; Reinwald, Mark; Nowak, Daniel.
Afiliación
  • Hecht A; Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany. anna.hecht@medma.uni-heidelberg.de.
  • Meyer JA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
  • Jann JC; Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany.
  • Sockel K; Department of Hematology, University Hospital Dresden, Dresden, Germany.
  • Giagounidis A; Department of Hematology, Oncology and Palliative Care, Marien Hospital Duesseldorf, Duesseldorf, Germany.
  • Götze KS; Department of Internal Medicine, Technical University of Munich, Munich, Germany.
  • Letsch A; Department of Hematology and Oncology, Charité, Benjamin Franklin University, Berlin, Germany.
  • Haase D; Clinics of Hematology and Medical Oncology, University Medicine Goettingen, Goettingen, Germany.
  • Schlenk RF; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
  • Haferlach T; MLL Munich Leukemia Laboratory, Munich, Germany.
  • Schafhausen P; Department of Oncology, Hematology, BMT with section Pneumology, Hubertus Wald Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Bug G; Department of Internal Medicine, University Hospital Frankfurt, Frankfurt, Germany.
  • Lübbert M; Internal Medicine, University Hospital Freiburg, Freiburg, Germany.
  • Thol F; Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
  • Büsche G; Hannover Medical School, Institute of Pathology, Hannover, Germany.
  • Schuler E; Department for Hematology, Oncology and Clinical Immunology, University Hospital, Heinrich-Heine-University, Duesseldorf, Germany.
  • Nowak V; Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany.
  • Obländer J; Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany.
  • Fey S; Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany.
  • Müller N; Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany.
  • Metzgeroth G; Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany.
  • Hofmann WK; Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany.
  • Germing U; Department for Hematology, Oncology and Clinical Immunology, University Hospital, Heinrich-Heine-University, Duesseldorf, Germany.
  • Nolte F; Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany.
  • Reinwald M; Brandenburg Medical School Theodor Fontane, Brandenburg an der Havel, Germany.
  • Nowak D; Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany.
Ann Hematol ; 100(6): 1463-1471, 2021 Jun.
Article en En | MEDLINE | ID: mdl-33903952
Myelodysplastic syndrome (MDS) with isolated deletion of chromosome 5q (MDS del5q) is a distinct subtype of MDS with quite favorable prognosis and excellent response to treatment with lenalidomide. Still, a relevant percentage of patients do not respond to lenalidomide and even experience progression to acute myeloid leukemia (AML). In this study, we aimed to investigate whether global DNA methylation patterns could predict response to lenalidomide. Genome-wide DNA methylation analysis using Illumina 450k methylation arrays was performed on n=51 patients with MDS del5q who were uniformly treated with lenalidomide in a prospective multicenter trial of the German MDS study group. To study potential direct effects of lenalidomide on DNA methylation, 17 paired samples pre- and post-treatment were analyzed. Our results revealed no relevant effect of lenalidomide on methylation status. Furthermore, methylation patterns prior to therapy could not predict lenalidomide response. However, methylation clustering identified a group of patients with a trend towards inferior overall survival. These patients showed hypermethylation of several interesting target genes, including genes of relevant signaling pathways, potentially indicating the evaluation of novel therapeutic targets.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes Mielodisplásicos / Metilación de ADN / Lenalidomida / Antineoplásicos Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Ann Hematol Asunto de la revista: HEMATOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes Mielodisplásicos / Metilación de ADN / Lenalidomida / Antineoplásicos Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Ann Hematol Asunto de la revista: HEMATOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania