Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia.

@article{Suzuki2005ClinicalCA,
  title={Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia.},
  author={Tatsuya Suzuki and Hitoshi Kiyoi and Kazutaka Ozeki and Akihiro Tomita and Satomi Yamaji and Ritsuro Suzuki and Yoshihisa Kodera and Shuichi Miyawaki and Norio Asou and Kazutaka Kuriyama and Fumiharu Yagasaki and Chihiro Shimazaki and Hideki Akiyama and Miki Nishimura and Toshiko Motoji and Katsuji Shinagawa and Akihiro Takeshita and Ryuzo Ueda and Tomohiro Kinoshita and Nobuhiko Emi and Tomoki Naoe},
  journal={Blood},
  year={2005},
  volume={106 8},
  pages={
          2854-61
        }
}
Recently, somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, have been reported in acute myeloid leukemia (AML). We analyzed the clinical significance of NPM1 mutations in comparison with cytogenetics, FLT3, NRAS, and TP53 mutations, and a partial tandem duplication of the MLL gene (MLL-TD) in 257 patients with AML. We found NPM1 mutations, including 4 novel sequence variants, in 64 of 257 (24.9%) patients. NPM1 mutations were associated… 

Figures and Tables from this paper

The frequency of NPM1 mutations in childhood acute myeloid leukemia
TLDR
The role of different types of NPM1 mutations, either individually or in the presence of other common gene mutations, may be essential for childhood AML prognosis.
Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML).
TLDR
It is revealed that patients having only an NPM1 mutation had a significantly better overall and disease-free survival and a lower cumulative incidence of relapse and the analysis of the clinical impact in 4 groups revealed this mutation appears to identify patients with improved response toward treatment.
The frequency of NPM 1 mutations in childhood acute myeloid leukemia
TLDR
The role of different types of NPM1 mutations, either individually or in the presence of other common gene mutations, may be essential for childhood AML prognosis.
NPM1 mutations in therapy-related acute myeloid leukemia with uncharacteristic features
TLDR
The close association toclass I mutations and the inverse association to class II mutations suggest mutations of NPM1 as representing a class II mutation-like abnormality in AML.
Prognostic Impact of NPM1 Mutations in Serbian Adult Patients with Acute Myeloid Leukemia
TLDR
The lack of impact or unfavorable prognostic effect of N PM1 mutations found in this study can be assigned to a small cohort of analyzed AML patients, as can the presence of FLT3 and IDH mutations or other genetic lesions that cooperate with NPM1 mutations influencing prognosis.
Prevalence and prognostic impact of NPM 1 mutations in 1485 adult patients with acute myeloid leukemia ( AML )
TLDR
Patients having only an NPM1 mutation had a significantly better overall and diseasefree survival and a lower cumulative incidence of relapse, and if not associated with FLT3-ITD mutations, mutant N PM1 appears to identify patients with improved response toward treatment.
Prognostic significance of NPM1 mutations in acute myeloid leukemia: A meta-analysis.
TLDR
A meta-analysis of nine studies suggests that the NPM1 mutation has a favorable effect on the outcome for AML, and may justify the risk-adapted therapeutic strategies according to the N PM1 status.
Clonal evolution patterns in acute myeloid leukemia with NPM1 mutation
TLDR
It is found that at relapse, some patients lose the NPM1 mutation and show distinct mutational and gene expression patterns, highlighting a potential route for relapse.
patients with acute myeloid leukemia ( AML ) mutations in 1485 adult NPM 1 Prevalence and prognostic impact
TLDR
It is revealed that patients having only an NPM1-mutation had a significantly better overall and disease free survival and a lower cumulative incidence of relapse, and if not associated with FLT3-ITD mutations, mutant N PM1 appears to identify patients with improved response towards treatment.
Identification of FLT3 and NPM1 Mutations in Patients with Acute Myeloid Leukaemia
TLDR
The optimized in-house PCR assays for the detection of FLT3-ITD, FLT 3-D835 and NPM1 mutations in AML patients were robust, less labour intensive and cost effective.
...
...

References

SHOWING 1-10 OF 53 REFERENCES
Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia.
TLDR
The FLT3 gene mutation, whose presence is detectable only by genomic polymerase chain reaction amplification and gel electrophoresis, might serve as an important molecular marker to predict the prognosis of patients with AML.
FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia.
TLDR
Results indicate that mutations in FLT3, RAS, or TP53 are common in older patients with AML and are associated with specific AML phenotypes as defined by laboratory values, cytogenetics, and clinical outcomes.
Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis.
TLDR
Data confirm that FLT mutations represent a common alteration in adult AML and a high mutant/wt ratio in ITD-positive patients appears to have a major impact on the prognostic relevance.
Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia
TLDR
Although there is an overlap in the mutational spectrum in AML with FLT3 ITD and MLL PTD mutations, the data do not support a common mechanistic basis and do not unequivocally support the notion that MLLPTD mutations represent an independent prognostic factor.
Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease.
TLDR
Besides the importance of FLT3-LM for biologic and clinical characterization of AML, its value as a marker for disease monitoring based on 120 follow-up samples of 34 patients is shown.
P53 gene mutations in acute myeloid leukemia with 17p monosomy.
TLDR
The fact that P53 gene mutations occurred more often in patients with 17p monosomy seems to support the "recessive" model of tumor suppressive activity of the P53 genes rather than the "dominant" model, in which alteration of only one allele is sufficient for the development of malignancy.
p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies.
TLDR
P53 mutations could induce drug resistance, at least in part, by interfering with normal apoptotic pathways in tumor cells, and are a strong prognostic indicator of response to chemotherapy and survival in AML, MDS, and CLL.
N-ras mutations in adult de novo acute myelogenous leukemia: prevalence and clinical significance.
TLDR
A comparison of patients with and without N-ras mutations showed no statistically significant differences in pretreatment clinical variables, response to induction therapy, or survival, except for a possibly higher percentage of FAB M4 subtypes in patients with the N-ra mutation.
Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia.
TLDR
Findings counter the prevailing bias that oncogene mutations lead to more aggressive behavior in human malignancies and suggest a longer survival in ras-positive patients.
Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype.
TLDR
Cytoplasmic NPM is a characteristic feature of a large subgroup of patients with AML who have a normal karyotype, NPM gene mutations, and responsiveness to induction chemotherapy.
...
...