title: Philadelphia-negative chronic myelogenous leukemia with breakpoint cluster region rearrangement: molecular analysis, clinical characteristics, and response to therapy.
abstract: We have detected rearrangement in the breakpoint cluster region (bcr) on chromosome 22 in cells derived from seven chronic myelogenous leukemia (CML) patients who had no cytogenetic evidence of a chromosome abnormality. These Philadelphia (Ph)-negative, bcr rearrangement-positive CML patients had clinical features and laboratory parameters that bore a strong resemblance to those of Ph-positive CML; all patients have shown a favorable response to hydroxyurea, busulphan, or alpha interferon (IFN-alpha) therapy. In one patient, because of the deletion of distal 3' sequences, detection of bcr rearrangement required a large probe that recognized proximal 5' sequences. Cells obtained from five patients were studied by Northern blotting and showed an aberrant 8 kilobase (kb) mRNA indistinguishable from the bcr-abl transcript that is felt to be a pathogenetic factor in Ph-positive CML. In three patients with a normal karyotype, bcr rearrangement was detected at the time of hematologic remission, and represented the only evidence for persistent malignancy. Our results suggest that: (1) the presence of bcr rearrangement in CML is associated with clinical features of Ph-positive disease, even in the absence of the Ph chromosome; (2) deletions occur within bcr and necessitate the use of probes covering both 5' and 3' DNA segments for accurate diagnosis; (3) molecular analysis may provide a useful approach to the follow-up of leukemia therapy in some patients; and (4) these patients respond to hydroxyurea, busulphan, and IFN-alpha therapy.
authors.affiliation: Department of Clinical Immunology and Biological Therapy, M.D. Anderson Hospital and Tumor Institute, Houston, TX 77030.
authors.forename: M
authors.initials: M
authors.lastname: Shtalrid
authors.forename: M
authors.initials: M
authors.lastname: Talpaz
authors.forename: M
authors.initials: M
authors.lastname: Blick
authors.forename: P
authors.initials: P
authors.lastname: Romero
authors.forename: H
authors.initials: H
authors.lastname: Kantarjian
authors.forename: K
authors.initials: K
authors.lastname: Taylor
authors.forename: J
authors.initials: J
authors.lastname: Trujillo
authors.forename: J
authors.initials: J
authors.lastname: Schachner
authors.forename: J U
authors.initials: JU
authors.lastname: Gutterman
authors.forename: R
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000293:Adolescent; D000328:Adult; D015139:Blotting, Southern; D002874:Chromosome Mapping; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007621:Karyotyping; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis
chemical_list: D015342:DNA Probes; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm