Pediatric T-cell lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation

Pediatric T-cell lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation

Kunz JB, Oct 2015, Haematologica (Link to abstract)


This study aimed to understand the genetic basis for relapse in T-cell ALL. Matched samples of T-cell ALL patients at diagnosis, remission and relapse where analyzed by various deep sequencing methods and DNA methylation array. The investigators found 2 mutation patterns at relapse. Type 1 was derived from major leukemic clones at diagnosis, with additional mutations. Type 2 arose from a common pre-leukemic ancestor, with the relapse clone having new mutations not similar to the major diagnostic clone. Overall there is significant increase in mutational load at relapse compared to first diagnosis. NT5C2 was identified as a recurrently mutated gene and may confer resistance to therapy. Relapse specific genetic changes tend to activate general mechanisms of carcinogenesis rather than known leukemia specific drivers. 


* This paper implies that there are at least two evolutionary pathways through which T-ALL can relapse.