A rare e14a3 (b3a3) BCR-ABL fusion transcript in chronic myeloid leukemia: Diagnostic challenges in clinical laboratory practice

Natini Jinawath, Alexis Norris-Kirby, B Douglas Smith, Christopher Gocke, Denise Batista, Constance A. Griffin, Kathleen M. Murphy

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)359-363
Number of pages5
JournalJournal of Molecular Diagnostics
Volume11
Issue number4
DOIs
StatePublished - Jul 2009

Fingerprint

Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Fluorescence In Situ Hybridization
Polymerase Chain Reaction
Cytogenetic Analysis
Gene Fusion
Reverse Transcriptase Polymerase Chain Reaction
DNA Sequence Analysis
Cytogenetics
Protein-Tyrosine Kinases
Introns
Disease Progression
Therapeutics
Genes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pathology and Forensic Medicine

Cite this

A rare e14a3 (b3a3) BCR-ABL fusion transcript in chronic myeloid leukemia : Diagnostic challenges in clinical laboratory practice. / Jinawath, Natini; Norris-Kirby, Alexis; Smith, B Douglas; Gocke, Christopher; Batista, Denise; Griffin, Constance A.; Murphy, Kathleen M.

In: Journal of Molecular Diagnostics, Vol. 11, No. 4, 07.2009, p. 359-363.

Research output: Contribution to journalArticle

@article{62079239e0f842baa8d6c5dea1ba21de,
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.",
author = "Natini Jinawath and Alexis Norris-Kirby and Smith, {B Douglas} and Christopher Gocke and Denise Batista and Griffin, {Constance A.} and Murphy, {Kathleen M.}",
year = "2009",
month = "7",
doi = "10.2353/jmoldx.2009.090008",
language = "English (US)",
volume = "11",
pages = "359--363",
journal = "Journal of Molecular Diagnostics",
issn = "1525-1578",
publisher = "Association of Molecular Pathology",
number = "4",

}

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

AU - Batista, Denise

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.

UR - http://www.scopus.com/inward/record.url?scp=69249097923&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69249097923&partnerID=8YFLogxK

U2 - 10.2353/jmoldx.2009.090008

DO - 10.2353/jmoldx.2009.090008

M3 - Article

C2 - 19497989

AN - SCOPUS:69249097923

VL - 11

SP - 359

EP - 363

JO - Journal of Molecular Diagnostics

JF - Journal of Molecular Diagnostics

SN - 1525-1578

IS - 4

ER -