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TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution.

Hou HA, Chou WC, Kuo YY, Liu CY, Lin LI, Tseng MH, Chiang YC, Liu MC, Liu CW, Tang JL, Yao M, Li CC, Huang SY, Ko BS, Hsu SC, Chen CY, Lin CT, Wu SJ, Tsay W, Chen YC, Tien HF - Blood Cancer J (2015)

Bottom Line: TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation.Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged.In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

ABSTRACT
The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.

No MeSH data available.


Related in: MedlinePlus

Patterns and locations of the TP53 mutations. The positions and predicted translational consequences of TP53 mutations detected in 500 AML samples are shown. The number of patients with the mutation is indicated in the parenthesis behind each mutation. The symbols ‘#', ‘*', ‘&', and ‘$' indicate that patients have two mutations.
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fig1: Patterns and locations of the TP53 mutations. The positions and predicted translational consequences of TP53 mutations detected in 500 AML samples are shown. The number of patients with the mutation is indicated in the parenthesis behind each mutation. The symbols ‘#', ‘*', ‘&', and ‘$' indicate that patients have two mutations.

Mentions: A total of 36 different TP53 mutations were identified in 35 patients (Table 1 and Figure 1). Of these, 28 were missense mutations, 2 were nonsense mutations, 5 were frame-shift mutations and 1 was in-frame mutation. V31I occurred in three patients, R175H and L194R in two each and all other mutations in only one each. Five patients had double heterozygous mutations (patients 1, 4, 14, 21 and 23). The remaining 30 patients showed only one mutation; all were heterozygous.


TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution.

Hou HA, Chou WC, Kuo YY, Liu CY, Lin LI, Tseng MH, Chiang YC, Liu MC, Liu CW, Tang JL, Yao M, Li CC, Huang SY, Ko BS, Hsu SC, Chen CY, Lin CT, Wu SJ, Tsay W, Chen YC, Tien HF - Blood Cancer J (2015)

Patterns and locations of the TP53 mutations. The positions and predicted translational consequences of TP53 mutations detected in 500 AML samples are shown. The number of patients with the mutation is indicated in the parenthesis behind each mutation. The symbols ‘#', ‘*', ‘&', and ‘$' indicate that patients have two mutations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526785&req=5

fig1: Patterns and locations of the TP53 mutations. The positions and predicted translational consequences of TP53 mutations detected in 500 AML samples are shown. The number of patients with the mutation is indicated in the parenthesis behind each mutation. The symbols ‘#', ‘*', ‘&', and ‘$' indicate that patients have two mutations.
Mentions: A total of 36 different TP53 mutations were identified in 35 patients (Table 1 and Figure 1). Of these, 28 were missense mutations, 2 were nonsense mutations, 5 were frame-shift mutations and 1 was in-frame mutation. V31I occurred in three patients, R175H and L194R in two each and all other mutations in only one each. Five patients had double heterozygous mutations (patients 1, 4, 14, 21 and 23). The remaining 30 patients showed only one mutation; all were heterozygous.

Bottom Line: TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation.Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged.In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

ABSTRACT
The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.

No MeSH data available.


Related in: MedlinePlus