Interphase cytogenetics and competitive RT-PCR for residual disease monitoring in patients with chronic myeloid leukaemia during interferon-alpha therapy.
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.
Tchirkov
A
A
Laboratoire de Cytogénétique Médicale, Faculté de Médecine, Clermont-Ferrand, France.
Giollant
M
M
Tavernier
F
F
Briançon
G
G
Tournilhac
O
O
Kwiatkowski
F
F
Philippe
P
P
Choufi
B
B
Deméocq
F
F
Travade
P
P
Malet
P
P
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
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl