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inv(16) and NPM1mut AMLs engraft human cytokine knock-in mice.
- Source :
-
Blood [Blood] 2016 Oct 27; Vol. 128 (17), pp. 2130-2134. Date of Electronic Publication: 2016 Aug 31. - Publication Year :
- 2016
-
Abstract
- Favorable-risk human acute myeloid leukemia (AML) engrafts poorly in currently used immunodeficient mice, possibly because of insufficient environmental support of these leukemic entities. To address this limitation, we here transplanted primary human AML with isolated nucleophosmin (NPM1) mutation and AML with inv(16) in mice in which human versions of genes encoding cytokines important for myelopoiesis (macrophage colony-stimulating factor [M-CSF], interleukin-3, granulocyte-macrophage colony-stimulating factor, and thrombopoietin) were knocked into their respective mouse loci. NPM1 <superscript>mut</superscript> AML engrafted with higher efficacy in cytokine knock-in (KI) mice and showed a trend toward higher bone marrow engraftment levels in comparison with NSG mice. inv(16) AML engrafted with high efficacy and was serially transplantable in cytokine KI mice but, in contrast, exhibited virtually no engraftment in NSG mice. Selected use of cytokine KI mice revealed that human M-CSF was required for inv(16) AML engraftment. Subsequent transcriptome profiling in an independent AML patient study cohort demonstrated high expression of M-CSF receptor and enrichment of M-CSF inducible genes in inv(16) AML cases. This study thus provides a first xenotransplantation mouse model for and informs on the disease biology of inv(16) AML.<br /> (© 2016 by The American Society of Hematology.)
- Subjects :
- Animals
Chromosome Aberrations
Chromosomes, Human, Pair 16 genetics
Cytokines
Gene Knock-In Techniques
Heterografts
Humans
Mice
Mutation
Nuclear Proteins genetics
Nucleophosmin
Disease Models, Animal
Leukemia, Myeloid, Acute genetics
Leukemia, Myeloid, Acute pathology
Neoplasm Transplantation methods
Transplantation, Heterologous methods
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 128
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 27581357
- Full Text :
- https://doi.org/10.1182/blood-2015-12-689356