The expression of ΔNTP73, TATP73 and TP53 genes in acute myeloid leukaemia is associated with recurrent cytogenetic abnormalities and in vitro susceptibility to cytarabine cytotoxicity

Abstract

TP73 encodes for two proteins: full-length TAp73 and DeltaNp73, which have little transcriptional activity and exert dominant-negative function towards TP53 and TAp73. We compared TATP73 and DeltaNTP73 expression in acute myeloid leukaemia (AML) samples and normal CD34(+) progenitors. Both forms were more highly expressed in leukaemic cells. Amongst AML blasts, TATP73 was more expressed in AML harbouring the recurrent genetic abnormalities (RGA): PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11, whereas higher DeltaNTP73 expression was detected in non-RGA cases. TP53 expression did not vary according to DeltaNTP73/TATP73 expression ratio. Leukaemic cells with higher DeltaNTP73/TATP73 ratios were significantly more resistant to cytarabine-induced apoptosis.