Phenotype in combination with genotype improves outcome prediction in acute myeloid leukemia: A report from children’s oncology group protocol AAML0531

Andrew P. Voigt, Lisa Eidenschink Brodersen, Todd A. Alonzo, Robert B. Gerbing, Andrew J. Menssen, Elisabeth R. Wilson, Samir Kahwash, Susana C. Raimondi, Betsy A. Hirsch, Alan S. Gamis, Soheil Meshinchi, Denise A. Wells, Michael R. Loken

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Diagnostic biomarkers can be used to determine relapse risk in acute myeloid leukemia, and certain genetic aberrancies have prognostic relevance. A diagnostic immunophenotypic expression profile, which quantifies the amounts of distinct gene products, not just their presence or absence, was established in order to improve outcome prediction for patients with acute myeloid leukemia. The immunophenotypic expression profile, which defines each patient’s leukemia as a location in 15-dimensional space, was generated for 769 patients enrolled in the Children’s Oncology Group AAML0531 protocol. Unsupervised hierarchical clustering grouped patients with similar immunophenotypic expression profiles into eleven patient cohorts, demonstrating high associations among phenotype, genotype, morphology, and outcome. Of 95 patients with inv(16), 79% segregated in Cluster A. Of 109 patients with t(8;21), 92% segregated in Clusters A and B. Of 152 patients with 11q23 alterations, 78% segregated in Clusters D, E, F, G, or H. For both inv(16) and 11q23 abnormalities, differential phenotypic expression identified patient groups with different survival characteristics (P<0.05). Clinical outcome analysis revealed that Cluster B (predominantly t(8;21)) was associated with favorable outcome (P<0.001) and Clusters E, G, H, and K were associated with adverse outcomes (P<0.05). Multivariable regression analysis revealed that Clusters E, G, H, and K were independently associated with worse survival (P range <0.001 to 0.008). The Children’s Oncology Group AAML0531 trial: clinicaltrials.gov Identifier: 00372593.

Original languageEnglish (US)
Pages (from-to)2058-2068
Number of pages11
JournalHaematologica
Volume102
Issue number12
DOIs
StatePublished - Nov 30 2017

Bibliographical note

Funding Information:
This work was supported by grants U10CA098543 (Chair’s grant), U10CA098413 (the Statistical Center Grant), U10CA180886 (NCTN Operations Center Grant), and U10CA180899 (NCTN Statistics & Data Center Grant).

Fingerprint Dive into the research topics of 'Phenotype in combination with genotype improves outcome prediction in acute myeloid leukemia: A report from children’s oncology group protocol AAML0531'. Together they form a unique fingerprint.

Cite this