Acute promyelocytic leukemia (APL) is commonly associated with t(15;17)(q24.1;q21.2), which results in the fusion of the promyelocytic leukemia (PML) gene at chromosome 15q24.1 with the retinoic acid receptor alpha (RARA) gene at chromosome 17q21.2.1 This fusion accounts for the disease response to all-trans retinoic acid (ATRA), and patients with APL usually have a favorable prognosis.1 However, although rare, RARA fuses with other genes in patients with APL, and reported partner genes include zinc finger and BTB domain containing 16 (ZBTB16, also known as promyelocytic leukemia zinc finger, PLZF),2,3 nucleophosmin (NPM1),4 nuclear mitotic apparatus (NUMA1),5 signal transducer and activator of transcription 5B (STAT5B),6 cAMP-dependent protein kinase type I-alpha regulatory subunit (PRKAR1A),7 FIP1-like 1 (FIP1L1),8 BCL6 corepressor (BCOR),9 and oligonucleotide/oligosaccharide-binding fold-containing 2A (OBFC2A).10 The identity of the partner gene is clinically important, because some RARA partner genes have been associated with resistance to ATRA therapy, in particular ZBTB16-RARA and STAT5B-RARA.3,6 This report presents a patient with APL for whom cytogenetic and molecular testing did not show evidence of t(15;17)(q24.1;q21.2)/PML-RARA, which led to the discovery of interferon regulatory factor 2 binding protein 2 (IRF2BP2), a novel gene partner for RARA.
Dr. Ravandi has disclosed that he receives research support from Sunesis Pharmaceuticals, Inc.; Bristol-Myers Squibb Company; Novartis AG; Seattle Genetics, Inc.; Merck & Co., Inc.; and Actinium Pharmaceuticals, Inc. He is on the advisory board for Sunesis Pharmaceuticals, Inc.; Amgen Inc.; Seattle Genetics, Inc. He receives honoraria from Sunesis Pharmaceuticals, Inc.; Seattle Genetics, Inc. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
The authors wish to thank Dr. Roger Schultz from Signature Genomics Laboratories for his assistance with oligonucleotide microarray analysis.
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