Figure 5.
Molecular characterization of lineage-switched MLL/AF4 leukemias. (A) Whole-exome–sequencing data showing genes recurrently mutated within the analyzed cohort and genes clonally mutated in relapsed cases belonging to the same function protein complexes (eg, DNA polymerases, epigenetic complexes, and transcriptional regulators). Data are presented according to the disease time point/cell lineage and age of the patient. Depicted are major SNVs/indels that were found in >30% of reads and minor SNVs/indels present in <30% reads. (B) Comparison of total mutation load (SNVs and indels) identified in patients at presentation (ALL) and relapse (AML) disease stage or lymphoid and myeloid fraction in MPALs. Listed are common SNVs predicted (by Condel scoring) to have deleterious effects. (C) Evolution of KRAS/NRAS mutation–carrying cells during the lineage-switching process. Clonal vs subclonal mutations were defined based on variant allele frequencies (VAFs) of identified hits at setup cutoff of 30%.