DR negativity is a distinctive feature of M1/M2 AML cases with NPM1 mutation

Syampurnawati, Meilani; Tatsumi, E; Ardianto, Bambang; Takenokuchi, Mariko; Nakamachi, Yuji; Kawano, Seiji; Kumagai, Shunichi; Saigo, Katsuyasu; Matsui, Toshimitsu; Takahashi, Takayuki; Nagai, Kenichi; Gunadi, Gunadi; Nishio, Hisahide; Yabe, Hiroki; Kondo, Shinichi; Hayashi, Yoshitake

doi:10.1016/j.leukres.2007.11.017

Cited by 22 publications

(12 citation statements)

References 13 publications

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“…However, neither a complete and characteristic immuno- Letters to the Editor phenotype nor a clear-cut genetic background has been observed in these studies. Syampurnawati et al 9 described cases with AML M1/M2 lacking the expression of HLA-DR in which NPM1 mutations were observed in 69%. Thus, a relation to the molecular genetic aberration, that is NPM1 mutation, was found; however, again the correlation was not complete and no comprehensive immunophenotype was described.…”

Section: Mll-ptdmentioning

confidence: 99%

Flow cytometric identification of acute myeloid leukemia with limited differentiation and NPM1 type A mutation: a new biologically defined entity

et al. 2009

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Section: Mll-ptdmentioning

confidence: 99%

Flow cytometric identification of acute myeloid leukemia with limited differentiation and NPM1 type A mutation: a new biologically defined entity

et al. 2009

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“…Myeloid and monocytic subtypes of NPM1 ‐mutated AML have been shown to demonstrate distinct immunophenotypes, beyond the expression of monocytic markers, suggesting there may be biologic differences between these two groups . Multiple studies have shown that, in addition to frequent expression of monocytic markers, NPM1 ‐mutated AMLs are predominantly negative for CD34 and often show negativity for HLA‐DR as well, potentially mimicking acute promyelocytic leukemia (APL) with PML‐RARA. Interestingly, previous work has shown improved outcomes in cases of AML that are negative for CD34 expression …”

Section: Introductionmentioning

confidence: 99%

A distinct immunophenotype identifies a subset of NPM1‐mutated AML with TET2 or IDH1/2 mutations and improved outcome

et al. 2018

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Recent work has identified distinct molecular subgroups of acute myeloid leukemia (AML) with implications for disease classification and prognosis. NPM1 is one of the most common recurrently mutated genes in AML. NPM1 mutations often co-occur with FLT3-ITDs and mutations in genes regulating DNA methylation, such as DNMT3A, TET2, and IDH1/2. It remains unclear whether these genetic alterations are associated with distinct immunophenotypic findings or affect prognosis. We identified 133 cases of NPM1-mutated AML and correlated sequencing data with immunophenotypic and clinical findings. Of 84 cases (63%) that lacked monocytic differentiation ("myeloid AML"), 40 (48%) demonstrated an acute promyelocytic leukemia-like (APL-like) immunophenotype by flow cytometry, with absence of CD34 and HLA-DR and strong myeloperoxidase expression, in the absence of a PML-RARA translocation. Pathologic variants in TET2, IDH1, or IDH2 were identified in 39/40 APL-like cases. This subset of NPM1-mutated AML was associated with longer relapse-free and overall survival, when compared with cases that were positive for CD34 and/or HLA-DR. The combination of NPM1 and TET2 or IDH1/2 mutations along with an APL-like immunophenotype identifies a distinct subtype of AML. Further studies addressing its biology and clinical significance may be especially relevant in the era of IDH inhibitors and recent work showing efficacy of ATRA therapy in NPM1 and IDH1-mutated AML.

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“…A number of studies have described the presence of common mutations within the final exon (exon-12) of the NPM1 gene in patients with AML [1,5,7-11]. These mutations cause the cytoplasmic localization of NPM and abrogate its function [12]. …”

Section: Introductionmentioning

confidence: 99%

The frequency of NPM1 mutations in childhood acute myeloid leukemia

et al. 2010

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BackgroundMutations in the nucleophosmin (NPM1) gene have been solely associated with childhood acute myeloid leukemia (AML). We evaluated the frequency of NPM1 mutations in childhood AML, their relation to clinical and cytogenetic features and the presence of common FLT3 and RAS mutations.ResultsNPM1 mutations were found in 8% of cases. They involved the typical type 'A' mutation and one novel mutation characterized by two individual base pair substitutions, which resulted in 2 amino acid changes (W290) and (S293) in the NPM protein. FLT3/ITD mutations were observed in 12% of the cases and in one NPM1-mutated case bearing also t(8;21) (q22;q22). No common RAS mutations were identified.ConclusionsA relatively consistent NPM1 mutation rate was observed, but with variations in types of mutations. 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.

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DR negativity is a distinctive feature of M1/M2 AML cases with NPM1 mutation

Cited by 22 publications

References 13 publications

Flow cytometric identification of acute myeloid leukemia with limited differentiation and NPM1 type A mutation: a new biologically defined entity

Flow cytometric identification of acute myeloid leukemia with limited differentiation and NPM1 type A mutation: a new biologically defined entity

A distinct immunophenotype identifies a subset of NPM1‐mutated AML with TET2 or IDH1/2 mutations and improved outcome

The frequency of NPM1 mutations in childhood acute myeloid leukemia

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