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Blood. 2016 Jan 28;127(4):458-63. doi: 10.1182/blood-2015-07-653840. Epub 2015 Nov 18.

Primary acute myeloid leukemia cells with overexpression of EVI-1 are sensitive to all-trans retinoic acid.

Author information

1
Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands; and.
2
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.

Abstract

Enhanced expression of ecotropic viral integration site 1 (EVI-1) occurs in ∼10% of acute myeloid leukemia (AML) patients and is associated with a very poor disease outcome. Patients with EVI-1-positive AML have poor initial responses to chemotherapy and high relapse rates, indicating an urgent need for alternative treatment strategies improving clinical outcome for these patients. Because treatment of acute promyelocytic patients with all-trans retinoic acid (ATRA) has improved the survival of these patients substantially, we investigated whether ATRA might also be effective for the subgroup of AML patients with EVI-1 overexpression. Here, we show that a substantial part of the EVI-1-positive AML cases respond to ATRA by induction of differentiation and decreased clonogenic capacity of myeloid blasts. Most importantly, we demonstrate that in vivo treatment of primary EVI-1-positive AML with ATRA leads to a significant reduction in leukemic engraftment. Altogether, our results show that a considerable part of the EVI-1-positive primary AML cases are sensitive to ATRA, suggesting that combining ATRA with the currently used conventional chemotherapy might be a promising treatment strategy decreasing relapse rates and enhancing complete remissions in this poor prognostic subgroup of AML patients.

PMID:
26582376
DOI:
10.1182/blood-2015-07-653840
[Indexed for MEDLINE]
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