• Medientyp: E-Artikel
  • Titel: NPM1 mutated AML can relapse with wild-type NPM1: persistent clonal hematopoiesis can drive relapse
  • Beteiligte: Höllein, Alexander; Meggendorfer, Manja; Dicker, Frank; Jeromin, Sabine; Nadarajah, Niroshan; Kern, Wolfgang; Haferlach, Claudia; Haferlach, Torsten
  • Erschienen: American Society of Hematology, 2018
  • Erschienen in: Blood Advances, 2 (2018) 22, Seite 3118-3125
  • Sprache: Englisch
  • DOI: 10.1182/bloodadvances.2018023432
  • ISSN: 2473-9529; 2473-9537
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  • Beschreibung: Abstract Acute myeloid leukemia (AML) with NPM1 mutation (NPM1mut) defines a World Health Organization entity. Absence of minimal residual disease (MRD) following induction chemotherapy is associated with an excellent prognosis. Data are conflicting on NPM1mut AML relapsing with wild-type NPM1 (NPM1wt). We analyzed 104 paired samples of NPM1mut AML patients with relapse and identified 14/104 that relapsed with NPM1wt AML. Blood counts at diagnosis differed significantly between patients with NPM1mut and NPM1wt relapse (median white blood cell count, 30 vs 3 × 109/L, P = .008; platelet count, 66 vs 128 × 109/l, P = .018). NPM1mut relapse occurred significantly earlier than NPM1wt relapse (14 vs 43 months, P = .004). At diagnosis, FLT3-ITD were more frequent in patients with NPM1mut relapse (P = .029), whereas DNMT3A mutations were more frequent in patients with NPM1wt relapse (P = .035). Sequencing analysis of paired samples at diagnosis, molecular remission, and NPM1wt relapse identified cooccurring mutations that persist from diagnosis throughout remission and at relapse, suggestive of a preexisting clonal hematopoiesis. We provide evidence that AML relapsing with NPM1wt is a distinct disease and that initial leukemia and relapse potentially arise from a premalignant clonal hematopoiesis.
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