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.
authors.affiliation: Division of Hematology and Ocology, Department of Medicine, Oregon Health & Science University, Portland 97201, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: O'Dwyer
authors.forename: K M
authors.initials: KM
authors.lastname: Gatter
authors.forename: M
authors.initials: M
authors.lastname: Loriaux
authors.forename: B J
authors.initials: BJ
authors.lastname: Druker
authors.forename: S B
authors.initials: SB
authors.lastname: Olson
authors.forename: R E
authors.initials: RE
authors.lastname: Magenis
authors.forename: H
authors.initials: H
authors.lastname: Lawce
authors.forename: M J
authors.initials: MJ
authors.lastname: Mauro
authors.forename: R T
authors.initials: RT
authors.lastname: Maziarz
authors.forename: R M
authors.initials: RM
authors.lastname: Braziel
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides; D016022:Case-Control Studies; D002898:Chromosomes, Human, Pair 8; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020732:Cytogenetic Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000235:genetics* / Q000473:pathology; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014314:Trisomy
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate