title: Cytogenetic response to alpha-interferon is predicted in early chronic phase chronic myeloid leukemia by M-bcr breakpoint location.
abstract: Alpha-interferon (alpha-IFN) therapy is an effective agent in early chronic phase (ECP) chronic myeloid leukemia (CML), achieving hematologic control in the majority and major cytogenetic response (MCR) (reduction in Ph' +ve metaphases to < 35%) in a substantial minority. Currently no pretreatment markers exist to ascertain likelihood of meaningful response. The site of breakpoint in M-bcr and relationship to prognosis is controversial. Studies have been hampered by variation in definition of breakpoint and difference in treatment protocols. In this study of ECP CML patients, Southern analysis and reverse transcription polymerase chain reaction (RT-PCR) were used to determine breakpoint location. Patients received alpha-IFN (9 x 10(6) units/day) and dose-adjusted hydroxyurea (HU) to maintain granulocyte count between 1.0-2.0 x 10(9)/l for 6 months or more. Twelve of 31 patients entered on the study achieved a MCR. The Sokal index did not predict for cytogenetic response to alpha-IFN. Eight of 11 patients with 5' breakpoint achieved MCR compared to only four of 20 patients with 3' breakpoint (P = 0.007). These results suggest site of M-bcr rearrangement may be predictive of response to alpha-IFN therapy. If verified by further study, this may allow more appropriate use of alpha-IFN with respect to other modalities such as allogeneic transplant.
authors.affiliation: Department of Haematology, Mater Misericordiae Hospital, Brisbane, Australia.
authors.forename: S L
authors.initials: SL
authors.lastname: Elliott
authors.forename: K M
authors.initials: KM
authors.lastname: Taylor
authors.forename: D L
authors.initials: DL
authors.lastname: Taylor
authors.forename: R L
authors.initials: RL
authors.lastname: Rodwell
authors.forename: B F
authors.initials: BF
authors.lastname: Williams
authors.forename: M M
authors.initials: MM
authors.lastname: Shuttlewood
authors.forename: S J
authors.initials: SJ
authors.lastname: Wright
authors.forename: P E
authors.initials: PE
authors.lastname: Eliadis
authors.forename: I H
authors.initials: IH
authors.lastname: Bunce
authors.forename: T J
authors.initials: TJ
authors.lastname: Frost
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D003582:Cytogenetics / Q000379:methods; D017931:DNA Primers; D015321:Gene Rearrangement; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000628:therapy*; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics*; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D011994:Recombinant Proteins; D015183:Restriction Mapping
chemical_list: D017931:DNA Primers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr