Transformation of human cd34+ hematopoietic progenitor cells with dek-nup214 induces aml in an immunocompromised mouse model

ABSTRACT Acute myeloid leukemia (AML) is a heterogeneous disease comprising a large number of subtypes defined by specific chromosome abnormalities. One such subtype carries the

t(6;9)(p22;q34) chromosome rearrangement, which leads to expression of the DEK-NUP214 chimeric gene, and has a particularly poor outcome. To provide a better understanding of the molecular

etiology of these relatively rare individual AML variants, it is necessary to generate _in vivo_ models, which can also serve as a means to evaluate targeted therapies based on their

specific genetic abnormalities. Here, we describe the development of a human cell AML, generated in CD34+ human hematopoietic progenitor cells xenografted into immunocompromised mice that

express human myeloid cell growth factors. Within 6 months, these mice develop a human cell AML with phenotypic characteristics of the primary t(6;9) disease and a CD45+CD13+CD34+CD38+

immunophenotype. Gene expression studies show that members of the HOX family of genes (HOXA9, 10, B3, B4 and PBX3) are highly upregulated in the AML from this mouse model as well as from

primary human t(6;9) AML. Gene expression analysis also identified several other significantly disregulated pathways involving KRAS, BRCA1 and ALK, for example. This is the first report of a

humanized model of the DEK-NUP214 disease and provides a means to study the development and treatment of this particular subtype of AML. Access through your institution Buy or subscribe

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leukemia. _Leukemia_ 2013; 27: 1000–1008. Article  CAS  PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Cancer Center, Georgia Regents University,,

Augusta,, GA, USA H Qin, J K Cowell & M Ren * Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA S Malek Authors * H Qin

View author publications You can also search for this author inPubMed Google Scholar * S Malek View author publications You can also search for this author inPubMed Google Scholar * J K

Cowell View author publications You can also search for this author inPubMed Google Scholar * M Ren View author publications You can also search for this author inPubMed Google Scholar

CORRESPONDING AUTHOR Correspondence to M Ren. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. ADDITIONAL INFORMATION Supplementary Information

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permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Qin, H., Malek, S., Cowell, J. _et al._ Transformation of human CD34+ hematopoietic progenitor cells with DEK-NUP214 induces AML in an

immunocompromised mouse model. _Oncogene_ 35, 5686–5691 (2016). https://doi.org/10.1038/onc.2016.118 Download citation * Received: 03 September 2015 * Revised: 02 February 2016 * Accepted:

12 February 2016 * Published: 11 April 2016 * Issue Date: 27 October 2016 * DOI: https://doi.org/10.1038/onc.2016.118 SHARE THIS ARTICLE Anyone you share the following link with will be able

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