title: Cytogenetic and molecular analysis in Philadelphia negative CML.
abstract: We studied the clinical, hematologic, cytogenetic and molecular biologic features in four patients with Philadelphia (Ph) negative chronic myeloid leukemia (CML). In all four cases the clinical and hematologic characteristics were indistinguishable from Ph positive CML. Cytogenetic analysis showed a normal karyotype in two patients and chromosomal translocations apparently not affecting chromosome 22 in the other two cases. Southern blot analysis using probes of the bcr region, demonstrated a bcr break-point in all four patients. In situ hybridization with bcr, c-abl, and c-sis probes showed unusual hybridization sites for 5'-bcr and c-abl indicating complex chromosomal rearrangements affecting three different chromosomes in the four patients investigated. Using polymerase chain reaction (PCR) followed by hybridization to oligonucleotide probes specific for the bcr-abl fusion region, the expression of a chimeric bcr-abl mRNA was detected. In these patients we demonstrated that (a) CML with a breakpoint in the bcr region without cytogenetically detectable Ph chromosome is characterized by the same genomic recombination of 5'-bcr and c-abl as CML with standard Ph translocation and (b) unusual localization of 5'-bcr and c-abl sequences caused by complex Ph translocation does not interfere with transcription of the bcr-abl fusion gene.
authors.affiliation: Department of Cell Biology & Genetics, Erasmus University, Rotterdam, The Netherlands.
authors.forename: D C
authors.initials: DC
authors.lastname: van der Plas
authors.forename: A B
authors.initials: AB
authors.lastname: Hermans
authors.forename: D
authors.initials: D
authors.lastname: Soekarman
authors.forename: E M
authors.initials: EM
authors.lastname: Smit
authors.forename: A
authors.initials: A
authors.lastname: de Klein
authors.forename: N
authors.initials: N
authors.lastname: Smadja
authors.forename: G
authors.initials: G
authors.lastname: Alimena
authors.forename: R
authors.initials: R
authors.lastname: Goudsmit
authors.forename: G
authors.initials: G
authors.lastname: Grosveld
authors.forename: A
authors.initials: A
authors.lastname: Hagemeijer
mesh_terms: D000328:Adult; D015139:Blotting, Southern; D003582:Cytogenetics; D004247:DNA; D005260:Female; D006801:Humans; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization
chemical_list: D004247:DNA