CD25 expression status improves prognostic risk classification in AML independent of established biomarkers

ECOG phase 3 trial, E1900

Mithat Gönen, Zhuoxin Sun, Maria E. Figueroa, Jay P. Patel, Omar Abdel-Wahab, Janis Racevskis, Rhett P. Ketterling, Hugo Fernandez, Jacob M. Rowe, Martin S. Tallman, Ari Melnick, Ross L. Levine, Elisabeth Paietta

Research output: Contribution to journalArticle

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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 CD25POS 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 CD25NEG 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 CD25POS 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 CD25POS 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.

Original languageEnglish (US)
Pages (from-to)2297-2306
Number of pages10
JournalBlood
Volume120
Issue number11
DOIs
StatePublished - Sep 13 2012

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Biomarkers
Stem cells
Acute Myeloid Leukemia
Gene expression
Interleukin-3 Receptor alpha Subunit
Daunorubicin
Oncology
Stem Cells
Interleukin-2 Receptors
Cytogenetics
Mutation
Granulocyte Precursor Cells
Transcriptome
Leukemia
Multivariate Analysis
Gene Expression
Survival

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Gönen, M., Sun, Z., Figueroa, M. E., Patel, J. P., Abdel-Wahab, O., Racevskis, J., ... Paietta, E. (2012). CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900. Blood, 120(11), 2297-2306. https://doi.org/10.1182/blood-2012-02-414425

CD25 expression status improves prognostic risk classification in AML independent of established biomarkers : ECOG phase 3 trial, E1900. / Gönen, Mithat; Sun, Zhuoxin; Figueroa, Maria E.; Patel, Jay P.; Abdel-Wahab, Omar; Racevskis, Janis; Ketterling, Rhett P.; Fernandez, Hugo; Rowe, Jacob M.; Tallman, Martin S.; Melnick, Ari; Levine, Ross L.; Paietta, Elisabeth.

In: Blood, Vol. 120, No. 11, 13.09.2012, p. 2297-2306.

Research output: Contribution to journalArticle

Gönen, M, Sun, Z, Figueroa, ME, Patel, JP, Abdel-Wahab, O, Racevskis, J, Ketterling, RP, Fernandez, H, Rowe, JM, Tallman, MS, Melnick, A, Levine, RL & Paietta, E 2012, 'CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900', Blood, vol. 120, no. 11, pp. 2297-2306. https://doi.org/10.1182/blood-2012-02-414425
Gönen, Mithat ; Sun, Zhuoxin ; Figueroa, Maria E. ; Patel, Jay P. ; Abdel-Wahab, Omar ; Racevskis, Janis ; Ketterling, Rhett P. ; Fernandez, Hugo ; Rowe, Jacob M. ; Tallman, Martin S. ; Melnick, Ari ; Levine, Ross L. ; Paietta, Elisabeth. / CD25 expression status improves prognostic risk classification in AML independent of established biomarkers : ECOG phase 3 trial, E1900. In: Blood. 2012 ; Vol. 120, No. 11. pp. 2297-2306.
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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 CD25POS 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 CD25NEG 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 CD25POS 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 CD25POS 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.",
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T2 - ECOG phase 3 trial, E1900

AU - Gönen, Mithat

AU - Sun, Zhuoxin

AU - Figueroa, Maria E.

AU - Patel, Jay P.

AU - Abdel-Wahab, Omar

AU - Racevskis, Janis

AU - Ketterling, Rhett P.

AU - Fernandez, Hugo

AU - Rowe, Jacob M.

AU - Tallman, Martin S.

AU - Melnick, Ari

AU - Levine, Ross L.

AU - Paietta, Elisabeth

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N2 - 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 CD25POS 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 CD25NEG 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 CD25POS 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 CD25POS 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.

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