Molecular profiling of patients with cytogenetically normal acute myeloid leukemia and hyperleukocytosis

Pastore, Friederike ; Pastore, Alessandro; Rothenberg-Thurley, Maja; Metzeler, Klaus H.; Ksienzyk, Bianka; Schneider, Stephanie; Bohlander, Stefan K.; Braess, Jan; Sauerland, Maria C.; Görlich, Dennis; Berdel, Wolfgang E.; Wörmann, Bernhard; Bergwelt-Baildon, Michael von; Hiddemann, Wolfgang und Spiekermann, Karsten (2022): Molecular profiling of patients with cytogenetically normal acute myeloid leukemia and hyperleukocytosis. In: Cancer, Bd. 128, Nr. 24: S. 4213-4222

Abstract

Background Acute myeloid leukemia (AML) with initial hyperleukocytosis is associated with high early mortality and a poor prognosis. The aims of this study were to delineate the underlying molecular landscape in the largest cytogenetic risk group, cytogenetically normal acute myeloid leukemia (CN-AML), and to assess the prognostic relevance of recurrent mutations in the context of hyperleukocytosis and clinical risk factors. Methods The authors performed a targeted sequencing of 49 recurrently mutated genes in 56 patients with newly diagnosed CN-AML and initial hyperleukocytosis of >= 100 G/L treated in the AMLCG99 study. The median number of mutated genes per patient was 5. The most common mutations occurred in FLT3 (73%), NPM1 (75%), and TET2 (45%). Results The predominant pathways affected by mutations were signaling (84% of patients), epigenetic modifiers (75% of patients), and nuclear transport (NPM1;75%) of patients. AML with hyperleukocytosis was enriched for molecular subtypes that negatively affected the prognosis, including a high percentage of patients presenting with co-occurring mutations in signaling and epigenetic modifiers such as FLT3 internal tandem duplications and TET2 mutations. Conclusions Despite these unique molecular features, clinical risk factors, including high white blood count, hemoglobin level, and lactate dehydrogenase level at baseline, remained the predictors for overall survival and relapse-free survival in hyperleukocytotic CN-AML.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0008-543X
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 468687596