Abstract |
We recently identified a new acute myeloid leukemia (AML) subtype characterized by mutations at exon-12 of the nucleophosmin (NPM) gene and aberrant cytoplasmic expression of NPM protein (NPMc+). NPMc+ AML accounts for about 35% of adult AML and it is associated with normal karyotype, wide morphological spectrum, CD34-negativity, high frequency of FLT3-ITD mutations and good response to induction therapy. In an attempt to identify a human cell line to serve as a model for the in vitro study of NPMc+ AML, we screened 79 myeloid cell lines for mutations at exon-12 of NPM. One of these cell lines, OCI/AML3, showed a TCTG duplication at exon-12 of NPM. This mutation corresponds to the type A, the NPM mutation most frequently observed in primary NPMc+ AML. OCI/AML3 cells also displayed typical phenotypic features of NPMc+ AML, that is, expression of macrophage markers and lack of CD34, and the immunocytochemical hallmark of this leukemia subtype, that is, the aberrant cytoplasmic expression of NPM. The OCI/AML3 cell line easily engrafts in NOD/SCID mice and maintains in the animals the typical features of NPMc+ AML, such as the NPM cytoplasmic expression. For all these reasons, the OCI/AML3 cell line represents a remarkable tool for biomolecular studies of NPMc+ AML.
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Authors | H Quentmeier, M P Martelli, W G Dirks, N Bolli, A Liso, R A F Macleod, I Nicoletti, R Mannucci, A Pucciarini, B Bigerna, M F Martelli, C Mecucci, H G Drexler, B Falini |
Journal | Leukemia
(Leukemia)
Vol. 19
Issue 10
Pg. 1760-7
(Oct 2005)
ISSN: 0887-6924 [Print] England |
PMID | 16079892
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, CD34
- Biomarkers
- NPM1 protein, human
- Nuclear Proteins
- Nucleophosmin
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Topics |
- Animals
- Antigens, CD34
(metabolism)
- Biomarkers
(metabolism)
- Cytoplasm
(metabolism)
- DNA Mutational Analysis
- Exons
(genetics)
- Gene Expression Regulation, Leukemic
- Humans
- Karyotyping
- Leukemia, Promyelocytic, Acute
(genetics, metabolism)
- Macrophages
(metabolism)
- Male
- Mice
- Mice, Inbred NOD
- Mice, SCID
- Middle Aged
- Mutation
(genetics)
- Nuclear Proteins
(genetics, metabolism)
- Nucleophosmin
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