title: Coding sequence and intron-exon junctions of the c-myb gene are intact in the chronic phase and blast crisis stages of chronic myeloid leukemia patients.
abstract: The c-myb gene encodes a transcription factor required for proliferation, differentiation and survival of normal and leukemic hematopoietic cells. c-Myb has a longer half-life in BCR/ABL-expressing than in normal cells, a feature which depends, in part, on PI-3K/Akt-dependent regulation of proteins interacting with the leucine zipper/negative regulatory region of c-Myb. Thus, we asked whether the stability of c-Myb in leukemic cells might be enhanced by mutations interfering with its degradation. We analyzed the c-myb gene in 133 chronic myeloid leukemia (CML) patients in chronic phase and/or blast crisis by denaturing-high performance liquid chromatography (D-HPLC) and sequence analysis of PCR products corresponding to the entire coding sequence and each exon-intron boundary. No mutations were found. We found four single nucleotide polymorphisms (SNPs) and identified an alternatively spliced transcript lacking exon 5, but SNPs frequency and expression of the alternatively spliced transcript were identical in normal and CML cells. Thus, the enhanced stability of c-Myb in CML blast crisis cells and perhaps in other types of leukemia is not caused by a genetic mechanism.
authors.affiliation: Department of Medical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Bussolari
authors.forename: O
authors.initials: O
authors.lastname: Candini
authors.forename: D
authors.initials: D
authors.lastname: Colomer
authors.forename: F
authors.initials: F
authors.lastname: Corradini
authors.forename: C
authors.initials: C
authors.lastname: Guerzoni
authors.forename: S A
authors.initials: SA
authors.lastname: Mariani
authors.forename: S
authors.initials: S
authors.lastname: Cattelani
authors.forename: C
authors.initials: C
authors.lastname: Silvestri
authors.forename: L
authors.initials: L
authors.lastname: Pecorari
authors.forename: I
authors.initials: I
authors.lastname: Iacobucci
authors.forename: S
authors.initials: S
authors.lastname: Soverini
authors.forename: T
authors.initials: T
authors.lastname: Fasano
authors.forename: G
authors.initials: G
authors.lastname: Martinelli
authors.forename: F
authors.initials: F
authors.lastname: Cervantes
authors.forename: B
authors.initials: B
authors.lastname: Calabretta
mesh_terms: D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D018450:Disease Progression; D005091:Exons; D005787:Gene Frequency; D006801:Humans; D007438:Introns; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D020598:Proto-Oncogene Proteins c-myb