The expression of DeltaNTP73, TATP73 and TP53 genes in acute myeloid leukaemia is associated with recurrent cytogenetic abnormalities and in vitro susceptibility to cytarabine cytotoxicity.
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.
Lucena-Araujo
Antonio R
AR
Haematology Division of the Department of Internal Medicine, Centre for Cell Based Therapy, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Panepucci
Rodrigo A
RA
dos Santos
Guilherme A S
GA
Jácomo
Rafael H
RH
Santana-Lemos
Bárbara A A
BA
Lima
Ana S G
AS
Garcia
Aglair B
AB
Araújo
Amélia G
AG
Falcão
Roberto P
RP
Rego
Eduardo M
EM
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002869:Chromosome Aberrations; D003561:Cytarabine / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D015321:Gene Rearrangement; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012008:Recurrence; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D000964:Antimetabolites, Antineoplastic; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D003561:Cytarabine