Activating mutations of receptor @entity4149 kinases (RTKs) and their downstream affectors are common in @entity3052 ( @entity3052 ). We performed mutational analysis of @entity7801 , @entity2467 , @entity6823 , vascular endothelial growth factor (VEGF) receptors ( @entity6758 , @entity319 [ @entity319 ]), and ras genes in a group of 91 pediatric @entity1 with @entity3052 treated on @entity1 's Cancer Group clinical trial CCG-2891. Forty-six percent of @entity1 had activating mutations of @entity7801 (24.5%), @entity2467 (3%), or ras (21%) genes. Mutation-positive @entity1 had a higher median diagnostic white blood cell (WBC) count (71.5 vs 19.6 x 10(9)/L; P =.005) and lower complete remission rate (55% versus 76%; P =.046) than mutation-negative @entity1 . The Kaplan-Meier estimate of overall survival (OS) for @entity1 with and without an activating mutation was 34% versus 57%, respectively (P =.035). However, within this group, @entity1 with @entity7801 /ALM (activation loop mutation) had good outcomes (OS, 86%). Exclusion of the @entity7801 /ALM from analysis decreased the OS for the remaining mutation-positive @entity1 to 26% (P =.003). Ten of the 23 mutation-positive and 11 of the 34 mutation-negative @entity1 received an allogeneic bone marrow transplant (BMT) in first complete remission (CR). In the mutation-positive group, the disease-free survival (DFS) for the allogeneic BMT recipients was 72% versus 23% for the 13 @entity1 who received chemotherapy or autologous BMT (P =.01). DFS for the mutation-free @entity1 with and without allogeneic BM transplantation was 55% and 40%, respectively (P =.38). Activating mutations in the RTK/ras signaling pathway are common in pediatric @entity3052 , and their presence may identify a population at higher risk of poor outcome who may benefit from allogeneic BM transplantation.

Activating mutations of RTK/ras signal transduction pathway in pediatric XXXX .

@entity1 :: ('9606', 'Species') :: ['patients', 'Children'] @entity6823 :: ('1436', 'Gene') :: ['c-fms'] @entity7801 :: ('2322', 'Gene') :: ['FLT3'] @entity3052 :: ('MESH:D015470', 'Disease') :: ['acute myeloid leukemia', 'AML'] @entity319 :: ('3791', 'Gene') :: ['KDR', 'kinase domain receptor'] @entity2467 :: ('3815', 'Gene') :: ['c-kit'] @entity6758 :: ('2321', 'Gene') :: ['Flt-1'] @entity4149 :: ('D014443', 'Chemical') :: ['tyrosine']
@entity3052 :: (MESH:D015470,Disease) :: ['acute myeloid leukemia']
