Immunophenotyping is a standard diagnostic procedure in leukemia, but unlike cytogenetic classifications, which are reliable indicators for prognostic interpretation, immunophenotyping has, thus far, yielded inconsistent results. Recently, the presence of CEBPA, NPM1, or FLT3 mutations, as a molecular characteristic, was identified as an important prognostic factor for normal karyotype (NK)-acute myeloid leukemia (AML). Because AML with the CEBPA mutation is closely associated with specific surface antigen expression, we investigated the prognostic implications and characteristics of a certain immunophenotype in NK-AML.
The frequency of CEBPA mutation according to cytogenetic classification in 318 AML patients was investigated, and then the surface antigen expression profile in NK-AML was assessed. Thereafter, the prognosis and patient characteristics of a specific immunophenotype was investigated in 329 NK-AML patients from the Japan Adult Leukemia Study Group (JALSG) AML97 study. Factor differences between groups of patients with and without this immunophenotype were compared by Fisher’s exact and Student’s t-tests. Complete remission (CR), disease-free survival (DFS), event-free survival (EFS) and overall survival (OS) was assessed using Fisher’s exact and log-rank tests. We used a multivariate Cox proportional hazard regression model to assess factors that could possibly affect the clinical outcome.
The CEBPA mutation, including 12 monoallelic and 29 biallelic mutations, was detected in 41 of the 318 AML patients. AML with the CEBPA mutation was frequently observed in NK-AML and in cytogenetically intermediate-risk AML, but rare in favorable- or adverse-risk AML. NK-AML with the CEBPA mutation was closely associated with CD4 negativity as well as CD7 and CD34 positivity in 133 NK-AML cases. Furthermore, CD15 positivity is known to be associated with the CEBPA mutation. Therefore, we investigated the prognostic implications and characteristics of the CD4- CD7+ CD15+ CD34+ immunophenotype in NK-AML in the JALSG AML97 study. NK-AML with the CD4- CD7+ CD15+ CD34+ immunophenotype was classified as the CEBPA type, and NK-AML without this immunophenotype was considered as the non-CEBPA type. Of the 329 NK-AML patients analyzed, 39 and 243 were classified as having CEBPA and non-CEBPA type NK-AML, respectively. NK-AML patients with CEBPA type tended to have better EFS and OS than those with non-CEBPA type (5-year EFS, 48.4% vs 30.6%, P = 0.039; 5-year OS, 67.3% vs 35.7%, P = 0.0019). Multivariate analysis showed that the CEBPA type and white blood cell (WBC) counts of >20 × 109/L were independent prognostic factors for better EFS and OS. Compared to non-CEBPA type NK-AML, CEBPA type was associated with higher MPO-positive rates, frequent presentation with Auer rods, and a FAB classification of M1 or M2.
NK-AML with the CD4- CD7+ CD15+ CD34+ immunophenotype is a clinically discrete entity, indicating the presence of the CEBPA mutation, which may have a possible role in risk stratification.
Asterisk with author names denotes non-ASH members.