Cytoplasmic nucleophosmin (cNPM) in acute myeloid leukaemia: Relation to disease characteristics

Kazem, Amani; Mikhael, Irene Lewis; Ghanem, Ahmed I

doi:10.1016/j.ajme.2011.07.015

Cited by 3 publications

(4 citation statements)

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“…Moreover, while a mutation at one location of the CEBPA gene does not assist as a prognostic factor, mutations at two locations, such as bi-allelic mutations involving an N-terminal mutation on one allele and a C-terminal mutation on the other (i.e., double mutations), are most often linked to a favorable prognosis. In the pioneering report on NPMc+ AML,Falini et al (2005) observed a high frequency of FLT3-ITD in patients with NPMc+ AML. This outcome has been established by studies on both adults and children, wherein approximately 40% of the patients with NPMc+ AML also had FLT3-ITD mutations, compared with approximately 15%-25% in patients with wtNPM.…”

mentioning

confidence: 99%

The potential role of nucleophosmin (NPM1) in the development of cancer

Dermani

Khoei

Afshar

et al. 2021

Journal Cellular Physiology

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Nucleophosmin (NPM1) is a well-known nucleocytoplasmic shuttling protein that performs several cellular functions such as ribosome biogenesis, chromatin remodeling, genomic stability, cell cycle progression, and apoptosis. NPM1 has been identified to be necessary for normal cellular functions, and its altered regulation by overexpression, mutation, translocation, loss of function, or sporadic deletion can lead to cancer and tumorigenesis. In this review, we focus on the gene and protein structure of NPM1 and its physiological roles. Finally, we discuss the association of NPM1 with various types of cancer including solid tumors and leukemia.

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confidence: 99%

The potential role of nucleophosmin (NPM1) in the development of cancer

Dermani

Khoei

Afshar

et al. 2021

Journal Cellular Physiology

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“…The N-terminal portion of NPM1 protein was important for oligomerization and chaperon activities (Herrera et al, 1996) and any mutation in this region cause defect in portion function. NPM1 mutations are restricted to exon 12 of AML patients (Kazem et al, 2011) and all mutations tend to defect NLS signal and modify it into new NES signal in exon 12, the NES signal was important in mutant NPM1 protein to accumulated the protein in the cytoplasm (Chou et al, 2006). More than 40 molecular variants of NPM1 mutations have been described in AML patients (Tan et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Limited studies were conducted in detecting mutations in NPM1 gene within exon 2 and/or exon 3 of AML patients. Both exons encoded for the N-terminal portion of NPM1 protein which plays a major role in protein oligomerization and chaperone activities (Herrera et al, 1996) also this region encode the Nuclear Export Signals (NES) that prove protein accumulation in the cytoplasm (Kazem et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Genetic Mutation Assessment of NPM1 Gene and Gene Expression of MDR1 in Iraqi Patients with Acute Myeloid Leukemia

Suleiman

Al-Saffar²,

Rafaa³

et al. 2018

OnLine Journal of Biological Sciences

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Since its discovery, mutations in NPM1 have been frequently associated with a large number of Acute Myeloid Leukemia (AML) patients. The vast majority of genetic changes were previously detected in exon 12, however little information report mutations in Nuclear Export Signal region (NES) of NPM1. Sequencing analysis included exon 2 and 3 for 75 Iraqi AML patients showed three SNPs, G/A792, G/A794 and G/A797 were detected within intron region of 90% AML and 70% healthy subjects. Other SNPs were only detected in AML subjects in which single nucleotide variant was identified in exon 3 of 70% AML subjects (A/G1275 rs753788683) in addition, two SNPs (G/A635 and G/A660) within intron region of 80% of AML subjects were detected. No genetic variation observed inexon 2 of amplified NPM1 gene. The correlation between MDR1 gene over expression and resistance to chemotherapy treatment showed no significant differences in gene expression between newly diagnosed and first-course induction subjects. Nevertheless, significant decreases in CT value were recorded for both the second induction AML and AML consolidation patients with p value of 0.0258 and 0.0007, respectively, as compared with healthy controls, indicating the induction of higher expression of MDR1 gene by increasing the challenge of AML patients with chemotherapy regimen.

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“…It can be noted that the most significant functions of the NPM1 are displacement of ribosomal components into the cytoplasm, control of centrosome duplication and RNA binding. 1,6 Approximately 50 molecular variants of NPM1 mutations have been identified so far; most of these mutations usually occur at the C-terminal of NPM1 exon-12. The arrangement of the NPM1 mutations at the C-terminal of NPM1 exon-12 leads to ectopic accumulation of mutant NPM1 in the cytoplasm of leukemic cells (NPMc+).…”

Section: International Journal Of Hematology and Oncologymentioning

confidence: 99%

Correlation of BCRP Expression to NPM1 Mutations in Acute Myeloid Leukemia

Keramati¹

2018

UHOD

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Nucleophosmin1 (NPM1) mutation is a new prognostic factor for acute myeloid leukemia. Significant complete remission after chemotherapy has been observed in patients with this mutation compared to non-mutated patients. Overexpression of breast cancer resistance protein (BCRP) is directly associated with multiple drug resistance in leukemia. The aim of this study was to identify the effect of normal and mutated NPM1 on the expression of BCRP in AML patients. This cross-sectional study was conducted on 80 AML patients and 20 healthy individuals as the control group between 2012 and 2017. NPM1 mutations were observed with the PCR technique and the BCRP expression was measured by real-time PCR. Screening of the 80 AML patients revealed NPM1 mutation in 9 (11.2%) of them. The average expression of BCRP decreased significantly in the AML patient group in com-parison with the control group (p< 0.001). No statistically significant difference was observed between NPM1 mutation and BCRP expression in both groups with and without NPM1 mutations (p= 0.394). Unlike other studies, no case of NPM1 mutation was reported in the M3 subtype. However, in this study, this mutation was observed in the M3 subtype, and should be investigated for genetic and racial factors' implication. There was no correlation between NPM1 mutation and BCRP expression. There are independently prognostic and treatment management factors in AML patients, which should be examined and considered in order to determine the treatment process and evaluation of drug resistance.

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Cytoplasmic nucleophosmin (cNPM) in acute myeloid leukaemia: Relation to disease characteristics

Cited by 3 publications

References 50 publications

The potential role of nucleophosmin (NPM1) in the development of cancer

The potential role of nucleophosmin (NPM1) in the development of cancer

Genetic Mutation Assessment of NPM1 Gene and Gene Expression of MDR1 in Iraqi Patients with Acute Myeloid Leukemia

Correlation of BCRP Expression to NPM1 Mutations in Acute Myeloid Leukemia

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