title: Interphase cytogenetics and competitive RT-PCR for residual disease monitoring in patients with chronic myeloid leukaemia during interferon-alpha therapy.
abstract: There is a need for fast and sensitive methods to evaluate the response of patients with chronic myeloid leukaemia (CML) to interferon-alpha (IFN-alpha) therapy to complement cytogenetic analysis of Philadelphia (Ph) chromosome-positive metaphases. We have used interphase FISH (fluorescence in situ hybridization) and competitive RT-PCR (reverse transcriptase-polymerase chain reaction) techniques for detection of BCR-ABL-positive cells to measure suppression of leukaemic clone in a series of 51 follow-up samples from 24 CML patients undergoing IFN-alpha treatment. Interphase FISH analysis of the malignant clone in bone marrow using BCR and ABL probes was found to be highly correlated to conventional G-banding metaphase examination (r = 0.98). RT-PCR quantification of BCR-ABL mRNA transcripts in blood also showed a high degree of concordance with the proportion of Ph-positive metaphases (r = 0.93). In addition, the degree of cytogenetic response did not influence the equivalence between karyotype analysis and molecular methods. We concluded that interphase FISH and competitive RT-PCR provide reliable information on residual tumour burden and response to IFN-alpha in CML patients. These molecular methods may significantly improve the efficiency of residual disease monitoring during IFN-alpha therapy of CML.
authors.affiliation: Laboratoire de Cytogénétique Médicale, Faculté de Médecine, Clermont-Ferrand, France.
authors.forename: A
authors.initials: A
authors.lastname: Tchirkov
authors.forename: M
authors.initials: M
authors.lastname: Giollant
authors.forename: F
authors.initials: F
authors.lastname: Tavernier
authors.forename: G
authors.initials: G
authors.lastname: Briançon
authors.forename: O
authors.initials: O
authors.lastname: Tournilhac
authors.forename: F
authors.initials: F
authors.lastname: Kwiatkowski
authors.forename: P
authors.initials: P
authors.lastname: Philippe
authors.forename: B
authors.initials: B
authors.lastname: Choufi
authors.forename: F
authors.initials: F
authors.lastname: Deméocq
authors.forename: P
authors.initials: P
authors.lastname: Travade
authors.forename: P
authors.initials: P
authors.lastname: Malet
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D016898:Interferon-alpha / Q000627:therapeutic use*; D007399:Interphase; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology / Q000628:therapy*; D015465:Leukemia, Myeloid, Accelerated Phase / Q000473:pathology / Q000628:therapy; D015466:Leukemia, Myeloid, Chronic-Phase / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction / Q000379:methods*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl