A rare e14a3 (b3a3) BCR-ABL fusion transcript in chronic myeloid leukemia: diagnostic challenges in clinical laboratory practice.
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.
Jinawath
Natini
N
Institute of Genetic Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Norris-Kirby
Alexis
A
Smith
B Douglas
BD
Gocke
Christopher D
CD
Batista
Denise A
DA
Griffin
Constance A
CA
Murphy
Kathleen M
KM
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
D016044:Fusion Proteins, bcr-abl