Chemotherapy and Mismatch Repair Deficiency Cooperate to Fuel TP53 Mutagenesis and ALL Relapse

Investigators provided direct evidence of a specific mechanism by which chemotherapy induced drug-resistance-associated mutations leading to relapse. Using genomic and functional analysis of relapsed acute lymphoblastic leukemia (ALL), they showed that thiopurine treatment in mismatch repair-deficient leukemias induced hotspot TP53 R248Q mutations through a specific mutational signature.