title: Clonal cytogenetic abnormalities in Philadelphia chromosome negative cells in chronic myeloid leukemia patients treated with imatinib.
abstract: Treatment of chronic myeloid leukemia (CML) with imatinib (Gleevec) induces a much higher rate of partial and complete cytogenetic responses (CCR) than interferon-alpha (IFN)-based therapies. Conventional wisdom suggests that elimination of the Philadelphia (Ph)- positive cells will lead to re-establishment of normal Ph-negative hematopoiesis. Surprisingly, karyotypic abnormalities were detected in the chromosome negative cells of some patients with cytogenetic response to imatinib. In some cases, this was associated with a myelodysplastic syndrome (MDS). While clonal evolution in Ph-positive cells is considered part of the progression of CML, clonal evolution in Ph-negative cells had been observed only rarely in a small number of patients treated with IFN or bone marrow transplantation, raising the question whether the phenomenon may be causally linked to imatinib therapy. In this manuscript, we will review the currently available data, suggest possible causes and discuss potential implications for patient management. We are fully aware that a systematic study of a larger patient cohort will be required to conclusively address these issues.
authors.affiliation: Department of Pathology and the Division of Hematology and Oncology, Oregon Health & Science University, Portland, Oregon 97239, USA. loriauxm@ohsu.edu
authors.forename: Marc
authors.initials: M
authors.lastname: Loriaux
authors.forename: Michael
authors.initials: M
authors.lastname: Deininger
mesh_terms: D001549:Benzamides; D016026:Bone Marrow Transplantation; D002869:Chromosome Aberrations; D015331:Cohort Studies; D018450:Disease Progression; D006410:Hematopoiesis; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000378:metabolism; D007621:Karyotyping; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000235:genetics; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate