Abstract
We determined the prognostic relevance of CD25 (IL-2 receptor-α) expression in 657 patients (≤ 60 years) with de novo acute myeloid leukemia (AML) treated in the Eastern Cooperative Oncology Group trial, E1900. We identified CD25
POS
myeloblasts in 87 patients (13%), of whom 92% had intermediate-risk cytogenetics. CD25 expression correlated with expression of stem cell antigen CD123. In multivariate analysis, controlled for prognostic baseline characteristics and daunorubicin dose, CD25
POS
patients had inferior complete remission rates (
P
= .0005) and overall survival (
P
< .0001) compared with CD25
NEG
cases. In a subset of 396 patients, we integrated CD25 expression with somatic mutation status to determine whether CD25 impacted outcome independent of prognostic mutations. CD25 was positively correlated with internal tandem duplications in
FLT3
(
FLT3-ITD
),
DNMT3A
, and
NPM1
mutations. The adverse prognostic impact of
FLT3-ITD
POS
AML was restricted to CD25
POS
patients. CD25 expression improved AML prognostication independent of integrated, cytogenetic and mutational data, such that it reallocated 11% of patients with intermediate-risk disease to the unfavorable-risk group. Gene expression analysis revealed that CD25
POS
status correlated with the expression of previously reported leukemia stem cell signatures. We conclude that CD25
POS
status provides prognostic relevance in AML independent of known biomarkers and is correlated with stem cell gene-expression signatures associated with adverse outcome in AML.
