The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases

• Published in: Leukemia Vol. 31; no. 3; pp. 705 - 711
• Main Authors: Stengel, A, Kern, W, Haferlach, T, Meggendorfer, M, Fasan, A, Haferlach, C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-03-2017; Nature Publishing Group
• Subjects: 14/32; 45/23; 45/77; 631/208/1405; 631/208/2489/68; 631/208/737; 692/699/1541; 692/699/1541/1990/283; 692/700/1750; Adolescent; Adult; Aged; Aged, 80 and over; Analysis; Apoptosis; Biopsy; Cancer; Cancer Research; Care and treatment; Cell cycle; Child; Child, Preschool; Chromosome Aberrations; Chronic lymphocytic leukemia; Critical Care Medicine; Development and progression; Disease; Female; Gene Deletion; Gene mutation; Genes; Genes, p53; Genetic aspects; Genetic Testing; Genomes; Health aspects; Hematologic diseases; Hematology; Humans; Immunophenotyping; Infant; Infant, Newborn; Intensive; Internal Medicine; Laboratories; Leukemia; Leukemia - diagnosis; Leukemia - epidemiology; Leukemia - genetics; Leukemia - mortality; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - mortality; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Male; Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Mutation; Myelodysplastic Syndromes - diagnosis; Myelodysplastic Syndromes - epidemiology; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - mortality; Neoplasms; Oncology; original-article; Population Surveillance; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality; Prognosis; Proteins; Survival; Tumor proteins; Young Adult; Germany
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2016.263

Alterations in
TP53
have been described in many cancer types including hematological neoplasms. We aimed at comparing
TP53
mutations (mut) and deletions (del) in a large cohort of patients with hematological malignancies (
n
=3307), including AML (
n
=858), MDS (
n
=943), ALL (
n
=358), CLL (
n
=1148). Overall, alterations in
TP53
were detected in 332/3307 cases (10%). The highest frequency was observed in ALL (total: 19%; mut+del: 6%; mut only: 8%; del only: 5%) and AML (total: 13%; mut+del: 5%; mut only: 7%; del only: 1%), whereas
TP53
alterations occurred less frequently in CLL (total: 8%) and MDS (total: 7%).
TP53
mutations were significantly more frequent in patients ⩾60 vs <60 years in AML (9% vs 2%,
P
<0.001) and ALL (12% vs 6%,
P
<0.001).
TP53
mut+del had a significant negative impact on overall survival in all entities, whereas differences were observed regarding
TP53
mut only or
TP53
del only:
TP53
mut only impacted survival in AML (36 vs 9 months,
P
<0.001) and MDS (65 vs 19 months,
P
<0.001),
TP53
del only in CLL (not reached vs 64 months,
P
=0.008) and MDS (65 vs 24 months,
P
=0.011). As substantial differences between the entities are observed regarding correlation to age and survival, we suggest evaluation of both
TP53
deletion and mutation status.