Radiotherapy‐related acute myeloid leukaemia with KMT2A amplification

Abstract

An 86-year-old male presented with three months of asthenia. He had a history of a vocal cord neoplasm eight years previously, which had been treated with radiotherapy. Physical examination showed only mucocutaneous pallor. Laboratory tests showed haemoglobin concentration 92 g/l, mean cell volume 101 fl, white blood cell count 1Á78 9 10 9 /l, neutrophils 0Á96 9 10 9 /l, lymphocytes 0Á44 9 10 9 /l and platelets 108 9 10 9 /l. Myeloblasts were present. Bone marrow aspiration showed marked hypocellularity with hypogranular and Pelgeroid neutrophils and 27Á7% blast cells, expressing CD34 and CD117. Bone marrow biopsy showed 10% cellularity with 20% CD34 + cells.The karyotype demonstrated a hypodiploid clone with numerous structural abnormalities, including 5q deletion, monosomy 7, triplication of part of 11q, a marker chromosome and a ring chromosome (left). Fluorescence in situ hybridization was compatible with deletion of EGR1, monosomy 7, RUNX1T1 trisomy, TP53 deletion and KMT2A (MLL) amplification in 50% of cells (right, dual-colour break-apart KMT2A probe). The patient was diagnosed with therapy-related acute myeloid leukaemia and showed a haematological and cytogenetic remission after one cycle of decitabine.KMT2A (located at 11q23) encodes a histone methyltransferase that has a role in epigenetic regulation of transcription, important for embryonic and haematopoietic development. Abnormalities of KMT2A, particularly rearrangements, are frequently seen in acute leukaemias. Amplification is a rare event and often associated with advanced age, a complex karyotype and a shorter overall survival. There is an association of KMT2A rearrangement with previous exposure to alkylating agents but whether there is a relationship of amplification to previous radiotherapy is unknown.