PhD, senior researcher
Russia 117997, Moscow, Samory Mashela st., 1+7 (909) 670-0045
Acute myeloid leukemia (AML) with t(8;21) or inv(16) have been considered as unique group within AML and are usually reported as core binding factor AML (CBF-AML) but there is significant clinical and biological heterogeneity within and relapse incidence reaches up to 40%. It is known that, translocations involving CBFs are not sufficient to induce fulminant leukemia alone, therefore is considered as a model for the multistep pathogenesis of AML. To characterize more broad spectrum of genetic changes we performed extensive mutational analysis of 54 genes by high-throughput sequencing in 30 patients with t(8;21)-AML. The molecular landscape of pediatric AML with t(8;21) was highly heterogeneous and harbored frequent mutations in genes activating tyrosine kinase signaling (including KIT, N/KRAS, and FLT3) – 60% in group with variable mutant allele ratios. Mutations in genes that regulate chromatin conformation or encode members of the cohesin complex were observed with high frequencies – 43% as well. These data support the theory of synergic cooperation between these events and suggest that diverse cooperating mutations may influence CBF-AML pathophysiology as well as clinical behavior and point to potential unique pathogenesis of t(8;21). The adoption of advances in DNA sequencing as a high-throughput sequencing technology is a useful tool in diagnostics of pediatric AML.