title: A rare e14a3 (b3a3) BCR-ABL fusion transcript in chronic myeloid leukemia: diagnostic challenges in clinical laboratory practice.
abstract: Patients with chronic myelogenous leukemia have a t(9;22)(q34;q11.2) or variant translocation that results in a BCR-ABL fusion gene. BCR-ABL detection by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) is the standard practice for monitoring residual disease in patients with chronic myelogenous leukemia who receive tyrosine kinase inhibitor therapies. In this study, we describe a patient who tested positive for the BCR-ABL translocation by fluorescence in situ hybridization and cytogenetic analysis but tested negative by qRT-PCR molecular analysis at the time of diagnosis. Further PCR analysis and DNA sequencing with alternative primer sets demonstrated the presence of an e14a3 (also known as b3a3) BCR-ABL fusion. The e14a3 fusion is rare, but may be underreported as a result of many commercially available and laboratory-developed primer sets that fail to detect breakpoints in the ABL gene that are downstream of intron 1. For this patient, if the qRT-PCR assay had been used to monitor disease response/progression after treatment and not in conjunction with fluorescence in situ hybridization or cytogenetics at the time of diagnosis, the negative result would have been misinterpreted as molecular remission.
authors.affiliation: Institute of Genetic Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Natini
authors.initials: N
authors.lastname: Jinawath
authors.forename: Alexis
authors.initials: A
authors.lastname: Norris-Kirby
authors.forename: B Douglas
authors.initials: BD
authors.lastname: Smith
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Gocke
authors.forename: Denise A
authors.initials: DA
authors.lastname: Batista
authors.forename: Constance A
authors.initials: CA
authors.lastname: Griffin
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000369:Aged, 80 and over; D002883:Chromosomes, Human, Pair 14; D020732:Cytogenetic Analysis; D004252:DNA Mutational Analysis; D005188:False Negative Reactions; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000235:genetics; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016044:Fusion Proteins, bcr-abl