Analysis of NPM1 Gene Mutations in Chinese Adults with Acute Myeloid Leukemia

Yan, Litao; Chen, Suning; Liang, Jin-Yu; Feng, Yufeng; He, Jun; Chang, Weirong; Zhu, Ziling; Pan, Jinlan; Wu, Yafang; Xue, Yongquan; Wu, Depei

doi:10.1532/ijh97.a10620

Cited by 16 publications

(28 citation statements)

References 11 publications

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“…However, our study demonstrated at least one patient with simultaneous co-expression of NPM1-A and RUNX1-RUNX1T1 transcripts. Occasionally, similar cases were reported by others, both in adults and children [18,21,23,30]. Errors in sample registration, PCR contamination, or other technical factors might explain these findings in some [29], but not all, of these cases.…”

Section: Discussionsupporting

confidence: 75%

“…The most prevalent types of mutations are mutation A (75%-80%), mutation B (10%), and mutation D (5%), while all other mutations are very rare [4,18]. To date, most studies have focused on the clinical and laboratory profile of all NPM1-mutated AML patients regardless of the type of the mutation, and, therefore, the clinical and laboratory characteristics of patients, particularly those with the most frequent type A mutations, have not been precisely recorded.…”

Section: Introductionmentioning

confidence: 99%

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NPM1 Gene Type A Mutation in Bulgarian Adults with Acute Myeloid Leukemia: A Single-Institution Study

Balatzenko¹,

Spassov²,

Stoyanov³

et al. 2014

Tjh

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Objective: Mutations of the nucleophosmin (NPM1) gene are considered as the most frequent acute myeloid leukemia (AML)-associated genetic lesion, reported with various incidences in different studies, and type A (NPM1-A) is the most frequent type. However, since most series in the literature report on the features of all patients regardless of the type of mutation, NPM1-A(+) cases have not been well characterized yet. Therefore, we evaluated the prevalence of NPM1-A in Bulgarian AML patients and searched for an association with clinical and laboratory features. Materials and Methods: One hundred and four adults (51 men, 53 women) were included in the study. NPM1-A status was determined using allele-specific reverse-transcription polymerase chain reaction with co-amplification of NPM1-A and β-actin and real-time quantitative TaqMan-based polymerase chain reaction. Patients received conventional induction chemotherapy and were followed for 13.2±16.4 months.Results: NPM1-A was detected in 26 (24.8%) patients. NPM1-A mutation was detected in all AML categories, including in one patient with RUNX1-RUNX1T1. There were no differences associated with the NPM1-A status with respect to age, sex, hemoglobin, platelet counts, percentage of bone marrow blasts, splenomegaly, complete remission rates, and overall survival. NPM1-A(+) patients, compared to NPM1-A(-) patients, were characterized by higher leukocyte counts [(75.4±81.9)x109/L vs. (42.5±65.9)x109/L; p=0.049], higher frequency of normal karyotype [14/18 (77.8%) vs. 26/62 (41.9%); p=0.014], higher frequency of FLT3-ITD [11/26 (42.3%) vs. 8/77 (10.4%); p=0.001], and lower incidence of CD34(+) [6/21 (28.8%) vs. 28/45 (62.2%); p=0.017]. Within the FLT3-ITD(-) group, the median overall survival of NPM1-A(-) patients was 14 months, while NPM1-A(+) patients did not reach the median (p=0.10). Conclusion: The prevalence of NPM1-A mutation in adult Bulgarian AML patients was similar to that reported in other studies. NPM1-A(+) patients were characterized by higher leukocyte counts, higher frequency of normal karyotypes and FLT3-ITD, and lower incidence of CD34(+), supporting the idea that the specific features of type A mutations might contribute to the general clinical and laboratory profile of NPM1(+) AML patients.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

NPM1 Gene Type A Mutation in Bulgarian Adults with Acute Myeloid Leukemia: A Single-Institution Study

Balatzenko¹,

Spassov²,

Stoyanov³

et al. 2014

Tjh

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“…The reasons for excluding articles are shown in Fig. 1 (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35).…”

Section: Methodsmentioning

confidence: 99%

Prognostic significance of NPM1 mutations in acute myeloid leukemia: A meta-analysis

Liu

et al. 2013

Molecular and Clinical Oncology

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Nucleophosmin 1 (NPM1) mutations have been identified in a substantial number of patients with acute myeloid leukemia (AML). Favorable outcomes in AML cases with NPM1 mutations have been previously reported. However, widely differing survival estimates have been indicated. Therefore, a meta-analysis of nine studies including a total of 4509 subjects was performed. The frequency of NPM1 mutations was found to be 6.45-56.08%. NPM1-mutation type (NPM1-mt) patients had >2-fold higher odds of achieving complete remission compared with NPM1-wild-type (NPM1-wt). The summary hazard ratio (HR) of NPM1-mt/NPM1-wt for disease-free survival (DFS) and OS was 0.67 and 0.63, respectively. In conclusion, these findings suggest that the NPM1 mutation has a favorable effect on the outcome for AML. The present meta-analysis was based on data abstracted from observational studies. However, the results obtained may justify the risk-adapted therapeutic strategies for AML according to the NPM1 status.

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“…[5][6][7] We report the first series of NPM1 mutation from the ethnically distinct Southeast Asian region, representing the largest series in Asia (n=400). The incidence of NPM1 mutation in Asian AML populations was previously known only from reports from China (n=28, 156), 19,20 Japan (n=257), 21 and Taiwan (n=173), 18 as summarized in Table 3. European reports were from Italy (n=107-2,562), 5,10,22,23 Germany (300-1,485), [7][8][9] and the Netherlands (n=275).…”

Section: Associated Genetic Abnormalities and Clinical Parameters Of mentioning

confidence: 99%

Nucleophosmin mutation in Southeast Asian acute myeloid leukemia: eight novel variants, FLT3 coexistence and prognostic impact of NPM1/FLT3 mutations

Boonthimat¹,

Thongnoppakhun²,

Auewarakul³

2008

Haematologica

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NPM1 mutations were investigated in 400 Southeast Asian leukemia patients and were detectable in 105 cases (26.25%) of acute myeloid leukemia but in no cases of acute lymphoid leukemia or chronic myeloid leukemia. Eight novel and 5 known mutations were identified. All predicted novel proteins shared the last five amino acids VSLRK with the similar gain of nuclear exporting signal motif as known variants. Older age, high white blood cell and platelet counts, normal cytogenetics, and CD34-negativity were associated with NPM1 mutation. FLT3 mutation was more frequent in mutant NPM1 than wild-type cases (56.8% vs. 25.6%) whereas RAS and AML1 mutations were rarely found. Overall survival analysis based on the NPM1/FLT3 mutational status revealed a better outcome for the NPM1-positive/FLT3-negative subgroup. We conclude that: i) NPM1 mutation represents a common genetic hallmark in Southeast Asian acute myeloid leukemia with a normal karyotype; ii) NPM1 mutants coexisted mainly with FLT3 mutants, but not RAS or AML1; iii) FLT3 mutation had a negative prognostic impact on patients with mutant NPM1.

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Analysis of NPM1 Gene Mutations in Chinese Adults with Acute Myeloid Leukemia

Cited by 16 publications

References 11 publications

NPM1 Gene Type A Mutation in Bulgarian Adults with Acute Myeloid Leukemia: A Single-Institution Study

NPM1 Gene Type A Mutation in Bulgarian Adults with Acute Myeloid Leukemia: A Single-Institution Study

Prognostic significance of NPM1 mutations in acute myeloid leukemia: A meta-analysis

Nucleophosmin mutation in Southeast Asian acute myeloid leukemia: eight novel variants, FLT3 coexistence and prognostic impact of NPM1/FLT3 mutations

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