Prognostic value of TP53 gene mutations in myelodysplastic syndromes and acute myeloid leukemia treated with azacitidine.
TP53 mutations are found in 5-10% of MDS and AML, where they are generally associated with complex karyotype and an overall poor prognosis. However, the impact of TP53 mutations in MDS treated with azacitidine (AZA) remains unclear. We analyzed TP53 mutations in 62 patients with high risk MDS or AML treated with AZA. A TP53 mutation was found in 23 patients (37.1%), associated with complex karyotype in 18 (78.3%) of them. TP53 mutations had no significant impact on response or complete response to AZA (p=0.60 and p=0.26, respectively). By univariate analysis, OS was negatively influenced by the presence of TP53 mutation (median OS 12.4 months versus 23.7 months, p<10(-4)), abnormal cytogenetics (median OS 14.4 months vs 33 months, p=0.02) complex cytogenetics (median OS 12.7 months versus 23.7 months, p=0.0005), and a diagnosis of AML (median 14.5 months vs 21.2 months for MDS or CMML, p=0.02). By multivariate analysis, only TP53 mutational status (HR 2.89 (95% confidence interval 1.38-6.04; p=0.005) retained statistical significance for OS. Results were similar when the analysis was restricted to MDS and CMML patients, excluding AML (HR=2.46 (95% confidence interval: 1.1-6.4); p=0.04)). Thus, TP53 mutations strongly correlated with poorer survival in higher risk MDS and AML treated with AZA.
Department of Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint Louis, Université Paris 7, France.
Cecile
C
Bally
Department of Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint Louis, Université Paris 7, France.
Lionel
L
Adès
Laboratoire d'Hématologie, Centre de Biologie-Pathologie, CHRU de Lille, France.
Aline
A
Renneville
Department of Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint Louis, Université Paris 7, France.
Marie
M
Sebert
Laboratoire d'Hématologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Bobigny, France.
Virginie
V
Eclache
Laboratoire d'Hématologie, Centre de Biologie-Pathologie, CHRU de Lille, France.
Claude
C
Preudhomme
Laboratory for Molecular Biology and Cytogenetics, Institut Paoli-Calmettes, Marseille, France.
Marie-Joelle
MJ
Mozziconacci
Univ Paris Diderot, Sorbonne Paris Cité, CNRS UMR7212/INSERM U944, Paris, France; AP-HP, Hôpital Saint Louis, 1 avenue Claude Vellfefaux, 75475 Paris, France.
Hugues
H
de The
Univ Paris Diderot, Sorbonne Paris Cité, CNRS UMR7212/INSERM U944, Paris, France; AP-HP, Hôpital Saint Louis, 1 avenue Claude Vellfefaux, 75475 Paris, France.
Jacqueline
J
Lehmann-Che
Department of Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint Louis, Université Paris 7, France. Electronic address: pierre.fenaux@sls.aphp.fr.
Pierre
P
Fenaux
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D005260:Female; D016158:Genes, p53; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011379:Prognosis
D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine
Acute myeloblastic leukemia; Azacitidine; Myelodysplastic syndromes; Prognostic factor; TP53 mutation