CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900 Journal Article

   

Authors:	Gonen, M.; Sun, Z.; Figueroa, M. E.; Patel, J. P.; Abdel-Wahab, O.; Racevskis, J.; Ketterling, R. P.; Fernandez, H.; Rowe, J. M.; Tallman, M. S.; Melnick, A.; Levine, R. L.; Paietta, E.
Article Title:	CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900
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, CD25POS 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-ITDPOS 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. © 2012 by The American Society of Hematology.
Keywords:	adolescent; adult; middle aged; survival analysis; young adult; acute granulocytic leukemia; major clinical study; overall survival; somatic mutation; leukemia, myeloid, acute; follow-up studies; antigen expression; cohort studies; gene expression; neoplasm proteins; tumor markers, biological; cytogenetics; dose-response relationship, drug; risk assessment; cancer genetics; correlation analysis; nucleotide sequence; daunorubicin; flt3 ligand; antibiotics, antineoplastic; interleukin 2 receptor alpha; interleukin-2 receptor alpha subunit; leukemia remission; gene expression regulation, leukemic; dna methyltransferase 3a; nucleophosmin; granulocyte precursor cells; myeloblast; cd123 antigen; interleukin-3 receptor alpha subunit
Journal Title:	Blood
Volume:	120
Issue:	11
ISSN:	0006-4971
Publisher:	American Society of Hematology
Date Published:	2012-09-13
Start Page:	2297
End Page:	2306
Language:	English
DOI:	10.1182/blood-2012-02-414425
PROVIDER:	scopus
PMCID:	PMC3447784
PUBMED:	22855599
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84866332779&partnerID=40&md5=2d1d87364926862a206c86e4e0a90aa5
Notes:	--- - "Export Date: 1 October 2012" - "CODEN: BLOOA" - "Source: Scopus"

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