Demonstration of Philadelphia chromosome negative abnormal clones in patients with chronic myelogenous leukemia during major cytogenetic responses induced by imatinib mesylate

M. E. O'Dwyer, Ken Gatter, Marc Loriaux, Brian Druker, Susan Olson, R. E. Magenis, H. Lawce, M. J. Mauro, Richard Maziarz, Rita Braziel

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Imatinib mesylate, an Abl-specific kinase inhibitor, produces sustained complete hematologic responses (CHR) and major cytogenetic responses (MCR) in chronic myeloid leukemia (CML) patients, but long-term outcomes in these patients are not yet known. This article reports the identification of clonal abnormalities in cells lacking detectable Philadelphia (Ph) chromosome/BCR-ABL rearrangements from seven patients with chronic- or accelerated-phase CML, who were treated with imatinib. All seven patients were refractory or intolerant to interferon therapy. Six of seven patients demonstrated MCR and one patient, who had a cryptic translocation, achieved low-level positivity (2.5%) for BCR-ABL by fluorescence in situ hybridization. The median duration of imatinib treatment before the identification of cytogenetic abnormalities in BCR-ABL-negative cells was 13 months. The most common cytogenetic abnormality was trisomy 8, documented in three patients. All patients had varying degrees of dysplastic morphologic abnormalities. One patient exhibited increased numbers of marrow blasts, yet consistently demonstrated no Ph-positive metaphases and the absence of morphologic features of CML. The presence of clonal abnormalities in Ph-negative cells of imatinib-treated CML patients with MCR and CHR highlights the importance of routine metaphase cytogenetic testing and long-term follow-up of all imatinib-treated patients.

Original languageEnglish (US)
Pages (from-to)481-487
Number of pages7
JournalLeukemia
Volume17
Issue number3
DOIs
StatePublished - Mar 1 2003

Fingerprint

Philadelphia Chromosome
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
Clone Cells
Metaphase
Chromosome Aberrations
Leukemia, Myeloid, Accelerated Phase
Imatinib Mesylate
Fluorescence In Situ Hybridization
Interferons
Phosphotransferases
Bone Marrow

Keywords

  • Clonal abnormalities
  • CML
  • Imatinib mesylate
  • MDS
  • ST1571

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

@article{c365829f46764126bc9b85f216fa02ba,
title = "Demonstration of Philadelphia chromosome negative abnormal clones in patients with chronic myelogenous leukemia during major cytogenetic responses induced by imatinib mesylate",
abstract = "Imatinib mesylate, an Abl-specific kinase inhibitor, produces sustained complete hematologic responses (CHR) and major cytogenetic responses (MCR) in chronic myeloid leukemia (CML) patients, but long-term outcomes in these patients are not yet known. This article reports the identification of clonal abnormalities in cells lacking detectable Philadelphia (Ph) chromosome/BCR-ABL rearrangements from seven patients with chronic- or accelerated-phase CML, who were treated with imatinib. All seven patients were refractory or intolerant to interferon therapy. Six of seven patients demonstrated MCR and one patient, who had a cryptic translocation, achieved low-level positivity (2.5{\%}) for BCR-ABL by fluorescence in situ hybridization. The median duration of imatinib treatment before the identification of cytogenetic abnormalities in BCR-ABL-negative cells was 13 months. The most common cytogenetic abnormality was trisomy 8, documented in three patients. All patients had varying degrees of dysplastic morphologic abnormalities. One patient exhibited increased numbers of marrow blasts, yet consistently demonstrated no Ph-positive metaphases and the absence of morphologic features of CML. The presence of clonal abnormalities in Ph-negative cells of imatinib-treated CML patients with MCR and CHR highlights the importance of routine metaphase cytogenetic testing and long-term follow-up of all imatinib-treated patients.",
keywords = "Clonal abnormalities, CML, Imatinib mesylate, MDS, ST1571",
author = "O'Dwyer, {M. E.} and Ken Gatter and Marc Loriaux and Brian Druker and Susan Olson and Magenis, {R. E.} and H. Lawce and Mauro, {M. J.} and Richard Maziarz and Rita Braziel",
year = "2003",
month = "3",
day = "1",
doi = "10.1038/sj.leu.2402848",
language = "English (US)",
volume = "17",
pages = "481--487",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Demonstration of Philadelphia chromosome negative abnormal clones in patients with chronic myelogenous leukemia during major cytogenetic responses induced by imatinib mesylate

AU - O'Dwyer, M. E.

AU - Gatter, Ken

AU - Loriaux, Marc

AU - Druker, Brian

AU - Olson, Susan

AU - Magenis, R. E.

AU - Lawce, H.

AU - Mauro, M. J.

AU - Maziarz, Richard

AU - Braziel, Rita

PY - 2003/3/1

Y1 - 2003/3/1

N2 - Imatinib mesylate, an Abl-specific kinase inhibitor, produces sustained complete hematologic responses (CHR) and major cytogenetic responses (MCR) in chronic myeloid leukemia (CML) patients, but long-term outcomes in these patients are not yet known. This article reports the identification of clonal abnormalities in cells lacking detectable Philadelphia (Ph) chromosome/BCR-ABL rearrangements from seven patients with chronic- or accelerated-phase CML, who were treated with imatinib. All seven patients were refractory or intolerant to interferon therapy. Six of seven patients demonstrated MCR and one patient, who had a cryptic translocation, achieved low-level positivity (2.5%) for BCR-ABL by fluorescence in situ hybridization. The median duration of imatinib treatment before the identification of cytogenetic abnormalities in BCR-ABL-negative cells was 13 months. The most common cytogenetic abnormality was trisomy 8, documented in three patients. All patients had varying degrees of dysplastic morphologic abnormalities. One patient exhibited increased numbers of marrow blasts, yet consistently demonstrated no Ph-positive metaphases and the absence of morphologic features of CML. The presence of clonal abnormalities in Ph-negative cells of imatinib-treated CML patients with MCR and CHR highlights the importance of routine metaphase cytogenetic testing and long-term follow-up of all imatinib-treated patients.

AB - Imatinib mesylate, an Abl-specific kinase inhibitor, produces sustained complete hematologic responses (CHR) and major cytogenetic responses (MCR) in chronic myeloid leukemia (CML) patients, but long-term outcomes in these patients are not yet known. This article reports the identification of clonal abnormalities in cells lacking detectable Philadelphia (Ph) chromosome/BCR-ABL rearrangements from seven patients with chronic- or accelerated-phase CML, who were treated with imatinib. All seven patients were refractory or intolerant to interferon therapy. Six of seven patients demonstrated MCR and one patient, who had a cryptic translocation, achieved low-level positivity (2.5%) for BCR-ABL by fluorescence in situ hybridization. The median duration of imatinib treatment before the identification of cytogenetic abnormalities in BCR-ABL-negative cells was 13 months. The most common cytogenetic abnormality was trisomy 8, documented in three patients. All patients had varying degrees of dysplastic morphologic abnormalities. One patient exhibited increased numbers of marrow blasts, yet consistently demonstrated no Ph-positive metaphases and the absence of morphologic features of CML. The presence of clonal abnormalities in Ph-negative cells of imatinib-treated CML patients with MCR and CHR highlights the importance of routine metaphase cytogenetic testing and long-term follow-up of all imatinib-treated patients.

KW - Clonal abnormalities

KW - CML

KW - Imatinib mesylate

KW - MDS

KW - ST1571

UR - http://www.scopus.com/inward/record.url?scp=0345382731&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0345382731&partnerID=8YFLogxK

U2 - 10.1038/sj.leu.2402848

DO - 10.1038/sj.leu.2402848

M3 - Article

C2 - 12646934

AN - SCOPUS:0345382731

VL - 17

SP - 481

EP - 487

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 3

ER -