Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/25689
Appears in Collections:Biological and Environmental Sciences Journal Articles
Peer Review Status: Refereed
Title: A case of AML characterized by a novel t(4;15)(q31;q22) translocation that confers a growth-stimulatory response to retinoid-based therapy
Authors: Watts, Justin M
Perez, Aymee
Pereira, Lutecia
Fan, Yao-Shan
Brown, Geoffrey
Vega, Francisco
Petrie, Kevin
Swords, Ronan T
Zelent, Arthur
Keywords: acute myeloid leukemia
t(4
15)(q31
q22)
TMEM154-RASGRF1
ATRA
retinoid
NCT02273102
Issue Date: 11-Jul-2017
Citation: Watts JM, Perez A, Pereira L, Fan Y, Brown G, Vega F, Petrie K, Swords RT & Zelent A (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), Art. No.: 1492.
Abstract: Here we report the case of a 30-year-old woman with relapsed acute myeloid leukemia (AML) who was treated with all-transretinoic 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 theTMEM154andRASGRF1genes. Analysis of primary cells from the patient revealed the expression ofTMEM154-RASGRF1mRNA and the resulting fusion protein, but no expression of the reciprocalRASGRF1-TMEM154fusion. 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.
DOI Link: http://dx.doi.org/10.3390/ijms18071492
Rights: © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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