TY - JOUR
T1 - A rare e14a3 (b3a3) BCR-ABL fusion transcript in chronic myeloid leukemia
T2 - Diagnostic challenges in clinical laboratory practice
AU - Jinawath, Natini
AU - Norris-Kirby, Alexis
AU - Smith, B. Douglas
AU - Gocke, Christopher D.
AU - Batista, Denise A.
AU - Griffin, Constance A.
AU - Murphy, Kathleen M.
PY - 2009/7
Y1 - 2009/7
N2 - 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.
AB - 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.
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U2 - 10.2353/jmoldx.2009.090008
DO - 10.2353/jmoldx.2009.090008
M3 - Article
C2 - 19497989
AN - SCOPUS:69249097923
SN - 1525-1578
VL - 11
SP - 359
EP - 363
JO - Journal of Molecular Diagnostics
JF - Journal of Molecular Diagnostics
IS - 4
ER -