NPM1 and CEBPA Mutations

Analysis of mutations in the nucleophosmin (NPM1) gene is important for the prognosis of patients with acute myeloid leukemia with normal cytogenetics (CN-AML). Almost 40 % of CN-AML patients have mutations in exon 12 of the NPM1 gene which result in the loss of tryptophan residues normally required for NPM1 binding to the nucleoli and in the generation of an additional nuclear export signal motif at the C-terminus of NPM1, which causes its abnormal cytoplasmic localization.

NPM1-mutated/FLT3-ITD negative patients are more likely responding to induction therapy and staying in remission. Moreover, NPM1 mutations may be used for minimal residual disease monitoring. The CCAAT/enhancer binding protein alpha (CEBPA) is the founding member of a family of related leucine zipper transcription factors that play important roles in myeloid differentiation. CEBPA mutations are found in 10–19 % of CN-AML patients. Favorable impact of CEBPA mutations was mainly observed in patients with biallelic mutations and with lack of FLT3-ITD. Our laboratory analyses of NPM1 and CEBPA mutations are performed in an accredited régime.