The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases.
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). TP53mut+del had a significant negative impact on overall survival in all entities, whereas differences were observed regarding TP53mut only or TP53del only: TP53mut only impacted survival in AML (36 vs 9 months, P<0.001) and MDS (65 vs 19 months, P<0.001), TP53del 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.
MLL Munich Leukemia Laboratory, Munich, Germany.
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A
Stengel
MLL Munich Leukemia Laboratory, Munich, Germany.
W
W
Kern
MLL Munich Leukemia Laboratory, Munich, Germany.
T
T
Haferlach
MLL Munich Leukemia Laboratory, Munich, Germany.
M
M
Meggendorfer
MLL Munich Leukemia Laboratory, Munich, Germany.
A
A
Fasan
MLL Munich Leukemia Laboratory, Munich, Germany.
C
C
Haferlach
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53; D005820:Genetic Testing; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D007938:Leukemia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000401:mortality; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality*; D011159:Population Surveillance; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D055815:Young Adult