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RUNX1-ETO deregulates the proliferation and growth factor responsiveness of human hematopoietic progenitor cells downstream of the myeloid transcription factor, MYCT1 [Letter]

Liddiard, Kate, Burnett, Alan Kenneth, Darley, Richard Lawrence and Tonks, Alex 2012. RUNX1-ETO deregulates the proliferation and growth factor responsiveness of human hematopoietic progenitor cells downstream of the myeloid transcription factor, MYCT1 [Letter]. Leukemia 26 (1) , pp. 177-179. 10.1038/leu.2011.188

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Abstract

To elucidate mechanisms by which RUNX1–ETO, the common acute myeloid leukemia t(8;21) fusion protein, primes hematopoietic cells for oncogenic transformation, we previously carried out Affymetrix gene expression profiling of RUNX1–ETO-expressing human CD34+ progenitor cells. We identified the MYC target gene, MYCT1, as a gene significantly upregulated at an early developmental stage that could be integral to RUNX1–ETO-mediated leukemic phenotype. To determine whether increased MYCT1 expression recapitulates the RUNX1–ETO phenotype, we performed retroviral transduction of MYCT1 as a single molecular abnormality into hematopoietic cell lines and normal human cord blood-derived CD34+ progenitor cells. In the absence of commercially available MYCT1 antibody, retroviral expression vectors, containing full-length MYCT1 coding sequence with (MYCT1-HA) or without (MYCT1) the addition of a C-terminal HA antigen tag, were also generated (Supplementary Materials and methods and Supplementary Figure S1), and transgenic MYCT1 over-expression was confirmed at the mRNA and protein levels (Supplementary Figure S2). Functional validation (Supplementary Figure S3) was provided by replication of the reduced viability of MYCT1-expressing murine myeloid 32D cells in the absence of WEHI-3B-conditioned medium reported by Yin et al.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher: Nature Publishing Group
ISSN: 0887-6924
Last Modified: 07 Jun 2019 20:35
URI: http://orca.cf.ac.uk/id/eprint/26951

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