Acute myeloid leukaemia post-cytotoxic therapy with BRAF V600E mutation in a child

Myeloid neoplasm post-cytotoxic therapy (MN-pCT) includes acute myeloid leukaemia (AML) arising in patients exposed to cytotoxic or radiation therapy for unrelated conditions. MN-pCT is rare in children and generally has a poor outcome. Mixed lineage leukaemia locus translocations (MLL/KMT2A) are the most common cytogenetic abnormalities associated with topoisomerase-II inhibitor exposure in MN-pCT.v-raf murine sarcoma viral oncogene homolog B1 (BRAF) are targetable mutations seen in <1% of de novo AML, but are associated with poor prognosis. BRAF mutations are extremely rare in MN-pCT and are described in few cases in adults and have not been reported in children.We present one such child with primary malignancy of B-ALL who was de novo ETV6/RUNX1 positive with absent Mixed lineage leukaemia (MLL) rearrangements. He had a late central nervous system relapse followed by MN-pCT (AML-M5) post-exposure to topoisomerase-II inhibitors and craniospinal irradiation (CSI). His cytogenetic work-up revealed t(9;11)(p21-22;q23) or (MLL/AF9) and targeted genomic sequencing revealed BRAFV600E. This case highlights the interplay of specific AML subtype, MLL rearrangement and BRAF mutation.