The frequency of NPM1 mutations in childhood acute myeloid leukemia

Braoudaki, Maria; Papathanassiou, Chrissa; Katsibardi, Κaterina; Tourkadoni, Natalia; Karamolegou, Kalliopi; Tzortzatou‐Stathopoulou, Fotini

doi:10.1186/1756-8722-3-41

Cited by 29 publications

(26 citation statements)

References 22 publications

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“…The association of NPM1 mutations and normal karyotype is well known [35], and was also observed in the present study. NPM1 carriers had higher platelet counts at diagnosis; however, when analyzing age groups separately, this association was significant in adults only, as already observed by Braoudaki et al [36] and Chauhan et al [34], although the group of positive children is too small for a conclusion to be drawn. There was an inverse relation between NPM1 and M3 FAB subtype; in fact, the NPM1 was observed neither in PML-RARa carriers nor in any of the patients carrying the gene fusions tested.…”

Section: Discussionsupporting

confidence: 63%

Molecular genetics and Cytogenetics data of 317 patients with de novo acute leukemia

Campos¹,

Melo²,

Duarte³

et al. 2015

Open J Hematol

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Background/Aims: Cytogenetic and molecular genetics play a pivotal role in treatment of acute leukemias. We prospectively evaluated genetic alterations in Brazilian patients with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) and their association with clinical and laboratorial data. Methods: Flow cytometry, conventional cytogenetics (CC), FISH, PCR, RT-PCR and sequencing were performed on samples from 161 de novo ALL and 155 AML.Results: Main CC findings in AML were t(15;17) (19.4%), +8 (17.4%), complex karyotype (14.6%), t(8;21) (7.6%); in ALL main CC findings were high hyperdiploidy (18.7%), low hyperdiploidy (9.7%), t(1;19) (9.7%), t(9;22) (8.2%). Frequencies of gene fusions and mutations in AML were PML-RARa 21.9%, RUNX1-RUNX1T1 7.1%, CBFB-MYH11 and MLL-AF9 2.6%, FLT3-ITD 14.2%, NPM1mut 13.6%. In ALL, ETV6-RUNX1 and BCR-ABL were present in 11.5% of the cases, TCF3-PBX1 in 10.8% and MLL-AF1 in 1.5%. Results were discordant between CC and RT-PCR in 3.6% of the cases. PML-RARa was associated with younger age, lower WBC and platelet; FLT3-ITD with higher hemoglobin and WBC; NPM1mut with higher platelet and WBC, older age and normal karyotype. BCR-ABL was associated with higher age; MLL-AF1 with higher WBC and EGIL BI-subtype. Conclusions:The incidence of some aberrations in AML differed from international literature. Discrepancies found between methodologies reinforce the importance of both CC and PCR in the diagnosis of leukemias.

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Section: Discussionsupporting

confidence: 63%

Molecular genetics and Cytogenetics data of 317 patients with de novo acute leukemia

Campos¹,

Melo²,

Duarte³

et al. 2015

Open J Hematol

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“…The role of different types of NPM1 mutation, either individually or in the presence of other common gene mutations was suggested to be essential also for childhood AML prognosis [18]. However, these studies generally compared the group of patients with the most frequent mutational type A versus a merged group of patients with other types of mutation.…”

Section: Introductionmentioning

confidence: 99%

Localization of AML-related nucleophosmin mutant depends on its subtype and is highly affected by its interaction with wild-type NPM

et al. 2017

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Mutations of the gene for nucleophosmin (NPM1) are the most frequent genetic aberration in patients with acute myeloid leukemia (AML). The mechanism of leukemic transformation in this leukemia subtype is not fully understood, but aberrant cytoplasmic localization of mutated NPM (NPMmut) is widely considered as an important factor for leukemia manifestation. We analyzed the subcellular localization of three types of NPM with a C-terminal mutation (A, B and E). Genes for the individual NPM forms were fused with a gene for one of fluorescent protein variants in plasmids, which were transfected into three cell lines with different endogenous NPM expression. Subcellular localization of the fluorescent protein-labeled NPM was further correlated with the relative expression of all NPM forms. We confirmed a high cytoplasmic expression of NPMmutA and NPMmutB whereas a substantial fraction of NPMmutE was found to be localized in nucleoli. Moreover, we revealed that the localization of fluorescently labeled NPM is affected by the interaction between various forms of the protein.

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“…The altered expression of genes, such as WT1 , SCL , and Notch1, that play crucial roles in the regulation of hematopoietic progenitor cell proliferation is frequently found in leukemia [1-7]. Increasing data show that the genes involved in hematopoietic stem/progenitor cell (HSPC) proliferation change their expression pattern during leukemogenesis [8].…”

Section: Introductionmentioning

confidence: 99%

The differential expression pattern of the BMI-1, SALL4 and ABCA3 genes in myeloid leukemia

Shen

Liu

et al. 2012

Cancer Cell Int

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Background and methodsIn order to characterize the expression pattern of SALL4, BMI-1 and ABCA3 genes in patients with myeloid leukemia and those who achieved complete remission (CR) after chemotherapy. Real-time PCR was used to determine the expression level of these genes in peripheral blood mononuclear cells from 24 patients with AML, eight patients with AML-CR, 13 patients with CML in the chronic phase (CML-CP), 12 patients with CML in blast crisis (CML-BC), 13 patients with CML-CR and 11 healthy individuals (HI).ResultsOverexpression of the BMI-1 gene was found in the AML, CML-CP and CML-BC groups as compared with HI group, while the BMI-1 expression level was lower in patients who achieved CR. In contrast, significantly increased SALL4 expression was only found in AML group, additionally, SALL4 expression was lower in the CML-CP and CML-CR groups compared with the HI group, while the SALL4 expression level in the CML-BC group was higher and significantly greater than that in the CML-CP and CML-CR groups. Moreover, a positive correlation between the expression of SALL4 and BMI-1 genes was found in samples from most groups. There was no significant difference of ABCA3 expression level in AML and CML-BC group in comparison with HI group. Interestingly, the ABCA3 expression level was significantly decreased in the CML-CP, AML-CR and CML-CR in comparison with the HI group. Moreover, the ABCA3 expression level in all of the CR groups was lower than that in their corresponding groups.ConclusionsThese results describe the altered SALL4, ABCA3 and BMI-1 expression pattern in different phases of myeloid leukemia, which may relate to the development and progression to different diseases. SALL4 expression was strongly correlated with BMI-1 in most of the myeloid leukemia patient groups, providing a potential link between SALL4 and BMI-1 in leukemogenesis.

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The frequency of NPM1 mutations in childhood acute myeloid leukemia

Cited by 29 publications

References 22 publications

Molecular genetics and Cytogenetics data of 317 patients with de novo acute leukemia

Molecular genetics and Cytogenetics data of 317 patients with de novo acute leukemia

Localization of AML-related nucleophosmin mutant depends on its subtype and is highly affected by its interaction with wild-type NPM

The differential expression pattern of the BMI-1, SALL4 and ABCA3 genes in myeloid leukemia

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