Abstract
Acute promyelocytic leukaemia (APL) is characterized by the PML/RARA fusion transcript. PML and RARA mutations have been shown to directly respond to arsenic trioxide (ATO) and all-trans retinoic (ATRA). We analysed the prevalence of PML mutations in 32 patients with de novo or therapy-related APL (t-APL; n = 5), treated with ATO. We identified one ATO-resistant t-APL patient, who presented a PML A216T mutation in both the rearranged and unrearranged PML alleles, and two mutations in the rearranged RARA gene. In this patient, subclones with different PML and RARA mutations acquired clonal dominance during the disease course, probably leading to treatment resistance.
Keywords:
ATO resistance; ATRA; PML and RARA mutations; acute promyelocytic leukaemia; clonal selection.
© 2016 John Wiley & Sons Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Alleles
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Antineoplastic Agents / therapeutic use
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Arsenic Trioxide
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Arsenicals / therapeutic use
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DNA Mutational Analysis / methods
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DNA, Neoplasm / genetics
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Drug Resistance, Neoplasm / genetics
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Female
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Gene Rearrangement
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Humans
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Leukemia, Promyelocytic, Acute / drug therapy
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Leukemia, Promyelocytic, Acute / genetics*
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Male
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Middle Aged
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Mutation*
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Neoplasm Proteins / genetics
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Nuclear Proteins / genetics*
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Oxides / therapeutic use
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Promyelocytic Leukemia Protein
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Receptors, Retinoic Acid / genetics
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Retinoic Acid Receptor alpha
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Transcription Factors / genetics*
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Tumor Suppressor Proteins / genetics*
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Young Adult
Substances
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Antineoplastic Agents
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Arsenicals
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DNA, Neoplasm
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Neoplasm Proteins
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Nuclear Proteins
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Oxides
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Promyelocytic Leukemia Protein
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RARA protein, human
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Receptors, Retinoic Acid
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Retinoic Acid Receptor alpha
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Transcription Factors
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Tumor Suppressor Proteins
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PML protein, human
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Arsenic Trioxide