Session: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster II
Hematology Disease Topics & Pathways:
AML, Diseases, Myeloid Malignancies
Methods: CD97 mRNA (RNA Seq V2 RSEM) expression and Z-score data was downloaded from TCGA. We generated Kaplan-Meier survival curves to compare overall (OS) and event-free (EFS) survival between patients with CD97 high (Z≥1) and CD97 low (Z<1) expression after stratification by age, cytogenetic status, transplant status and NPM1 mutation status. Association between CD97 expression and patient clinical and molecular characteristics was performed by Mann-Whitney U’s non-parametric t-test and Fisher’s exact test. STATA 12.0 SE was used to perform a Cox Proportional Hazards Model.
Results: Patients with cytogenetically normal AML (CN-AML) had significantly higher CD97 expression than cytogenetically abnormal AML (CA-AML) (1.31 fold, p=0.023). Patients with high CD97 expression had significantly higher WBC count (median: 56.1 vs 13.1, p=0.004) and % bone marrow blasts (median: 83 vs 71%, p=0.019). CD97 was significantly higher in patients with NPM1 mutation (n=48) compared with patients with NPM1 wild type (n=125) (1.56 fold, p<0.000). CD97 was also significantly higher in patients with FLT3 mutation (ITD and point mutations) (n=49) compared with patients with FLT3 wild type (n=124) (1.4 fold, p=0.0008). Additionally, CD97 was significantly lower in the patients with RUNX1 mutation (n=17) compared with wildtype gene (n=156) (42.1% lower; p=0.0002).
The OS of the CD97 high was significantly shorter than that of the CD97 low patients (median: 7.35 vs. 24.1 months; p=0.0015). Patients with CD97 high expression had significantly shorter EFS than that of CD97 low (median: 5.35 vs. 12 months; p=0.0015). Furthermore, in CN-AML CD97 high patients had shorter OS than CD97 low patients in CN-AML (median: 7.5 vs 20.5 months; p=0.0045; Figure 3B). In multivariate survival analysis, CD97 high expression was associated with shorter OS when adjusted for age, cytogenetic risk and transplant status (HR= 1.96; 95% Cl: 1.19-3.24; p=0.009).
Because CD97 expression was associated with NPM1 mutation in AML, we stratified patients according to NPM1 mutational status and found that in patients with wildtype NPM1, CD97 high expression was associated with significantly shorter OS (Median survival: 6.35 vs 22.3 months; P= 0.0081) and EFS (Median survival: 5.35 vs 13.4 months; P=0.0006). In patients with NPM1 mutation, a similar but not significant association was observed with CD97 high expression and shorter OS (median survival: 7.5 vs 24.1 months; P=0.1) and EFS (median survival: 5.8 vs 11.1 months; P=0.27).
Furthermore, in patients ≥ 60; CD97 high expression was associated with shorter OS compared with CD97 low (median survival 3.3 vs 11 months; p=0.0019) and EFS (Median survival 2.9 vs 9.2 months; p=0.0092). Similar but not significant association was observed in in patients<60 (Median OS: 27.5 vs 53.9; p=0.2) and (Median EFS 8.5 vs 53.9; p=0.2).
Conclusion: Patients with high CD97 expression had shorter OS and EFS. CD97 was higher in CN-AML compared with CA-AML patients. Additionally, high CD97 was also associated with NPM1 mutation. Our findings demonstrate that CD97 expression contributes to the clinical outcome of patients with AML, particularly in older patients. This study provides rationale for further functional and mechanistic studies aiming to understand the role of CD97 in AML.
Disclosures: No relevant conflicts of interest to declare.
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