We determined the prognostic relevance of CD25 (IL-2 receptor-␣) 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. (Blood. 2012;120(11):2297-2306)
IntroductionIncreasingly, recurrent genetic aberrations govern the prognostication of the acute leukemias, including the large group of patients who present with acute myeloid leukemia (AML) without apparent cytogenetic abnormalities. A steadily growing catalog of molecular lesions has led to the development of outcome-based classification systems that incorporate information on perturbed pathogenetic pathways and inform us about potential therapeutic targets. [1][2][3][4] In the context of this evolving molecular risk assessment, antigenexpression profiles have been identified as surrogates for certain leukemic genotypes. Furthermore, a few single antigens per se have been found to be predictive of clinical response. In most cases, however, the prognostic power of antigens has not been disassociated from underlying genetic determinants.The prognostic impact of antigens, such as CD1a and CD13, in T-lineage acute lymphoblastic leukemia (ALL) 5 has been linked to molecular subgroups with the activation of specific transcription factors and with unique gene expression signatures, reflecting distinct stages of maturation. 6 In acute promyelocytic leukemia (APL), expression of the T cell-affiliated antigen, CD2, in association with S-isoform PML/RAR␣, 7 confers inferior prognosis. 8 CD2 POS S-isoform POS APL is distinguishable from other isoforms on the basis of gene-expression profiling (GEP) 9 and has been posited to be derived from an immature leukemia stem cell (LSC). 10 Su...