Unsupervised hierarchical clustering of surface antigen expression to identify normal karyotype AML patients with distinct disease characteristics and poor outcome.

• DOI: 10.1200/jco.2017.35.15_suppl.7042
• Publication Date: 2018-09-06T15:50:36Z
• Authors: Madlen Jentzsch; Marius Bill; Luba Schuhmann; Juliane Grimm; Julia Schulz; Karoline Schubert; Maria Knyrim; Laura Schmalbrock; Stefanie Beinicke; Janine Häntschel; Wolfram Pönisch; Vladan Vucinic; Georg-Nikolaus Fr...; Gerhard Behre; Dietger Niederwieser; Sebastian Schwind
• Keywords: Cluster of differentiation

7042 Background: Surface antigen expression evaluation is part of the standard work-up at acute myeloid leukemia (AML) diagnosis. The biological & prognostic implications surface patterns in normal karyotype (NK) AML patients (pts) remain unknown. Methods: diagnostic mononuclear cells bone marrow (BM) 111 NK-AML pts were assessed using a flow cytometric panel. At diagnosis common gene mutations (mut) levels analyzed. Pts received stem cell transplantation (SCT, 98% allogeneic, 2% autologous; median age 63 years [y, range 26-74y]) after induction therapy our institution. Median follow up was 3.3y. With R’s gplot package unsupervised hierarchical clustering antigens performed revealed 4 distinct clusters. Results: cluster 1 (n = 36) had higher immature, 2 31) thrombocytic/T-cell/erythroid, 3 24) monocytic 20) antigens. All clusters associated with clinical molecular features. diagnosis, compared to all others, CD34+/CD38- burden ( P< .001), blood blasts .03) BM .06) by trend. They less NPM1 mut .001) DNMT3A P= .02), more likely be EVI1 positive EZH2 RUNX1 .009), BAALC ERG .02) MN1 expression. Compared cumulative incidence relapse (CIR, .002, 1y 41% vs 15%) shorter event-free survival (EFS, .02, 50% 69%). In multivariate analysis, significantly CIR (Hazard Ratio [HR] 5.4, .01) adjustment for FLT3-ITD EFS (HR 2.1, FLT3-ITD, disease status SCT. Conclusions: high immature (eg CD34, CD117, CD13), genes involved renewal worse outcome. Our data indicate relationship between easily accessible features aggressiveness phenotype.