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A Case of AML Characterized by a Novel t(4;15)(q31;q22) Translocation That Confers a Growth-Stimulatory Response to Retinoid-Based Therapy.

Watts, Justin M, Perez, Aymee, Pereira, Lutecia, Fan, Yao-Shan, Brown, Geoffrey, Vega, Francisco, Petrie, Kevin, Swords, Ronan T and Zelent, Arthur (2017) A Case of AML Characterized by a Novel t(4;15)(q31;q22) Translocation That Confers a Growth-Stimulatory Response to Retinoid-Based Therapy. International journal of molecular sciences, 18 (7). ISSN 1422-0067

Item Type: Article

Abstract

Here we report the case of a 30-year-old woman with relapsed acute myeloid leukemia (AML) who was treated with all- retinoic acid (ATRA) as part of investigational therapy (NCT02273102). The patient died from rapid disease progression following eight days of continuous treatment with ATRA. Karyotype analysis and RNA-Seq revealed the presence of a novel t(4;15)(q31;q22) reciprocal translocation involving the and genes. Analysis of primary cells from the patient revealed the expression of mRNA and the resulting fusion protein, but no expression of the reciprocal fusion. Consistent with the response of the patient to ATRA therapy, we observed a rapid proliferation of t(4;15) primary cells following ATRA treatment ex vivo. Preliminary characterization of the retinoid response of t(4;15) AML revealed that in stark contrast to non-t(4;15) AML, these cells proliferate in response to specific agonists of RARα and RARγ. Furthermore, we observed an increase in the levels of nuclear RARγ upon ATRA treatment. In summary, the identification of the novel t(4;15)(q31;q22) reciprocal translocation opens new avenues in the study of retinoid resistance and provides potential for a new biomarker for therapy of AML.

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More Information

Depositing User: Kevin Petrie

Identifiers

Item ID: 12447
Identification Number: https://doi.org/10.3390/ijms18071492
ISSN: 1422-0067
URI: http://sure.sunderland.ac.uk/id/eprint/12447
Official URL: https://www.mdpi.com/1422-0067/18/7/1492

Users with ORCIDS

ORCID for Kevin Petrie: ORCID iD orcid.org/0000-0002-9805-9152

Catalogue record

Date Deposited: 18 Aug 2020 19:11
Last Modified: 30 Sep 2020 10:49

Contributors

Author: Kevin Petrie ORCID iD
Author: Justin M Watts
Author: Aymee Perez
Author: Lutecia Pereira
Author: Yao-Shan Fan
Author: Geoffrey Brown
Author: Francisco Vega
Author: Ronan T Swords
Author: Arthur Zelent

University Divisions

Faculty of Health Sciences and Wellbeing > School of Medicine

Subjects

Sciences > Biomedical Sciences
Sciences > Health Sciences

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