High PRDM16 expression identifies a prognostic subgroup of pediatric acute myeloid leukaemia correlated to FLT3‐ITD,KMT2A‐PTD, and NUP98‐NSD1: the results of the Japanese Paediatric Leukaemia/Lymphoma Study Group AML‐05 trial

Summary Recent reports described the NUP 98‐ NSD 1 fusion as an adverse prognostic marker for acute myeloid leukaemia ( AML ) and PRDM 16 (also known as MEL 1 ) as the representative overexpressed gene in patients harbouring NUP 98‐ NSD 1 fusion. PRDM 16 gene expression levels were measured via real‐time polymerase chain reaction in 369 paediatric patients with de novo AML , of whom 84 (23%) exhibited PRDM 16 overexpression ( PRDM 16 / ABL 1 ratio ≥ 0·010). The frequencies of patients with high or low PRDM 16 expression differed widely with respect to each genetic alteration, as follows: t(8;21), 4% vs. 96%, P < 0·001; inv(16), 0% vs. 100%, P < 0·001; KMT 2A (also termed MLL )‐ partial tandem duplication, 100% vs. 0%, P < 0·001; NUP 98 ‐ NSD 1 , 100% vs. 0%, P < 0·001. The overall survival ( OS ) and event‐free survival ( EFS ) among PRDM 16‐ overexpressing patients were significantly worse than in patients with low PRDM 16 expression (3‐year OS : 51% vs. 81%, P < 0·001, 3‐year EFS : 32% vs. 64%, P < 0·001) irrespective of other cytogenetic alterations except for NPM 1 . PRDM 16 gene expression was particularly useful for stratifying FLT 3 ‐internal tandem duplication‐positive AML patients (3‐year OS : high = 30% vs. low = 70%, P < 0·001). PRDM 16 overexpression was highly recurrent in de novo paediatric AML patients with high/intermediate‐risk cytogenetic profiles and was independently associated with an adverse outcome.