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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

Kaplan–Meier survival curves for OS and DFS in a total of 363 AML patients (a, b), 36 patients with unfavorable-risk cytogenetics (c, d) and 28 patients with complex karyotype (e, f) who received standard intensive chemotherapy.
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fig2: Kaplan–Meier survival curves for OS and DFS in a total of 363 AML patients (a, b), 36 patients with unfavorable-risk cytogenetics (c, d) and 28 patients with complex karyotype (e, f) who received standard intensive chemotherapy.

Mentions: Of the 363 AML patients undergoing conventional intensive induction chemotherapy, 284 (78.5%) patients achieved a CR. TP53 mutation was associated with an inferior response rate (CR rate 28.6% vs 80.2%, P<0.0001) and higher probability to be refractory to treatment (50% vs 13.5%, P=0.0017). With a median follow-up of 55 months (range, 1.0–160), patients with TP53 mutation had significantly poorer OS and DFS than those without TP53 mutation (median, 5 vs 35 months, P<0.001, and median, 0 vs 9 months, P<0.001, respectively, Figures 2a and b). In the subgroups of 36 patients with unfavorable-risk cytogenetics, the differences in OS and DFS were still significant between patients with and without TP53 mutation (median, 9.5 vs 14 months, P=0.001, Figure 2c and median, 0 vs 2.5 months, P= 0.015, Figure 2d, respectively). The same was also true for the subgroup of 28 patients with CK (median, 9 vs 14 months, P=0.003, Figure 2e and median, 0 vs 2 months, P=0.021, Figure 2f, respectively). Intriguingly, among the patients without TP53 mutation, the OS is similar between those with intermediate-risk cytogenetics and unfavorable-risk cytogenetics (P=0.304).


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)

Kaplan–Meier survival curves for OS and DFS in a total of 363 AML patients (a, b), 36 patients with unfavorable-risk cytogenetics (c, d) and 28 patients with complex karyotype (e, f) who received standard intensive chemotherapy.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Kaplan–Meier survival curves for OS and DFS in a total of 363 AML patients (a, b), 36 patients with unfavorable-risk cytogenetics (c, d) and 28 patients with complex karyotype (e, f) who received standard intensive chemotherapy.
Mentions: Of the 363 AML patients undergoing conventional intensive induction chemotherapy, 284 (78.5%) patients achieved a CR. TP53 mutation was associated with an inferior response rate (CR rate 28.6% vs 80.2%, P<0.0001) and higher probability to be refractory to treatment (50% vs 13.5%, P=0.0017). With a median follow-up of 55 months (range, 1.0–160), patients with TP53 mutation had significantly poorer OS and DFS than those without TP53 mutation (median, 5 vs 35 months, P<0.001, and median, 0 vs 9 months, P<0.001, respectively, Figures 2a and b). In the subgroups of 36 patients with unfavorable-risk cytogenetics, the differences in OS and DFS were still significant between patients with and without TP53 mutation (median, 9.5 vs 14 months, P=0.001, Figure 2c and median, 0 vs 2.5 months, P= 0.015, Figure 2d, respectively). The same was also true for the subgroup of 28 patients with CK (median, 9 vs 14 months, P=0.003, Figure 2e and median, 0 vs 2 months, P=0.021, Figure 2f, respectively). Intriguingly, among the patients without TP53 mutation, the OS is similar between those with intermediate-risk cytogenetics and unfavorable-risk cytogenetics (P=0.304).

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