Disease Characteristics and Prognostic Implications of Cell-Surface FLT3 Receptor (CD135) Expression in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group

Katherine Tarlock, Todd A. Alonzo, Michael R. Loken, Robert B. Gerbing, Rhonda E. Ries, Richard Aplenc, Lillian Sung, Susana C. Raimondi, Betsy A. Hirsch, Samir B. Kahwash, Amy McKenney, E. Anders Kolb, Alan S. Gamis, Soheil Meshinchi

The FLT3 cell-surface receptor tyrosine kinase (CD135) is expressed in a majority of both acute lymphoid leukemia (ALL) and myeloid leukemia (AML). However, the prognostic significance of CD135 expression in AML remains unclear. We therefore evaluated the association between FLT3 surface expression and disease characteristics and outcomes in pediatric patients with AML. We analyzed FLT3 receptor expression on AML blasts by multi-dimensional flow cytometry and its association with disease characteristics, clinical outcomes, and FLT3 transcript level in 367 children with AML treated on the Children's Oncology Group trial AAML0531. There was high variability in blast CD135 cell-surface expression across specimens. CD135 expression measure by flow cytometry was not correlated with FLT3 transcript expression determined by quantitative RT-PCR. Overall, CD135 expression was not significantly different for patients with FLT3/WT and those with FLT3/ITD and FLT3/ALM (p=0.25). High cell-surface CD135 expression was associated with FAB M5 subtype (p<0.001), KMT2A rearrangements (p=0.009) and inversely associated with inv(16)/t(16;16) (p< 0.001). Complete remission rate, overall survival, disease-free survival, and relapse rates were not significantly different between patients with low and high CD135 expression. FLT3 cell-surface expression did not vary by FLT3 mutational status, but high FLT3 expression was strongly associated with KMT2A rearrangements. Our study found that there was no prognostic significance of FLT3 expression in pediatric AML.