Transformation of human CD34+ hematopoietic progenitor cells with DEK-NUP214 induces AML in an immunocompromised mouse model

H. Qin, S. Malek, John Kenneth Cowell, Mingqiang Ren

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5686-5691
Number of pages6
JournalOncogene
Volume35
Issue number43
DOIs
StatePublished - Oct 27 2016

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Hematopoietic Stem Cells
Acute Myeloid Leukemia
Gene Expression
Human Development
Myeloid Cells
Chromosome Aberrations
Genes
Intercellular Signaling Peptides and Proteins
Chromosomes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Transformation of human CD34+ hematopoietic progenitor cells with DEK-NUP214 induces AML in an immunocompromised mouse model. / Qin, H.; Malek, S.; Cowell, John Kenneth; Ren, Mingqiang.

In: Oncogene, Vol. 35, No. 43, 27.10.2016, p. 5686-5691.

Research output: Contribution to journalArticle

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