Studies on CEBPA mutations in acute myeloid leukaemia

摘要: Acute myeloid leukaemia (AML) is a highly heterogeneous disease with regard to clinical outcome, and molecular markers prognostic impact can be used stratify patients for risk-adapted therapy. CEBPA mutations have been associated favourable prognosis, however several questions remained, in particular whether one (CEBPA-single) or two (CEBPA-double) were necessary this benefit, their interaction other markers. A method of detecting patient samples using denaturing HPLC was developed the status 1427 young adult AML (median age 43 years, range 15-68 years) determined. Overall, 107 (7%) CEBPA-mutant: 48 (45%) CEBPA-single 59 (55%) CEBPA-double. The majority CEBPA-double (83%) had an out-of-frame insertion/deletion N-terminus mutation C-terminal DNA-binding/leucine zipper domains (DBD/LZD) that on different alleles as determined by cloning. By contrast, cases distributed across gene. less likely FLT3/ITD (P=.04) unlikely NPM1 (P<.0001) compared CEBPA-WT/CEBPA-single cases. Eight year overall survival (OS) higher CEBPA-WT (54%, 34%, 31%, respectively, P=.004). In multivariate analyses, CEBPA-double, but not CEBPA-single, independent factor OS (P=.004) relapse (P=.02). However, benefit completely lost presence FLT3/ITD. mutant level 101 fragment analysis consistent heterozygous present most cells. ten atypical C/EBPα transactivation activity explored luciferase reporter assay. Only affecting DBD LZD functional activity. This work provides insight into biology use