title: Philadelphia chromosome and monosomy 7 in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study.
abstract: During an 8-year period, 3,638 children from institutions of the Pediatric Oncology Group (POG) were diagnosed with acute lymphoblastic leukemia (ALL). Fifty-seven patients had Philadelphia chromosome-positive (Ph1) ALL. Blast cells obtained at diagnosis from 13 of these 57 cases (23%) were also found to have partial or complete monosomy 7 (-7). This subgroup of children with Ph1/-7 ALL was comprised primarily of older males with early B-lineage ALL. Bone marrow specimens from six Ph1/-7 patients were studied further using the polymerase chain reaction and primers that flank the ALL, and chronic myelogenous leukemia breakpoints to determine the molecular characteristic of the 9;22 translocation. Rearrangements were detected in RNA from bone marrow and/or peripheral blood cells of six patients, although four were in hematologic remission at the time of the analysis. Five cases showed the ALL breakpoint, while one child with Ph1/-7 showed the chronic myelogenous leukemia breakpoint. The induction failure rate was much higher in this subgroup (31%) as compared with Ph1-negative cases, and the projected duration of event-free survival reflected the aggressive nature of this subgroup because no children are projected to remain in remission at 2 years. ALL with both the 9;22 translocation and -7 appears to represent a unique and previously undescribed subgroup of childhood ALL associated with a particularly adverse outcome. Leukemic transformation in such patients may involve the interaction of a dominant oncogene (Ph1) and a tumor suppressor gene (-7).
authors.affiliation: Stanford University School of Medicine, CA.
authors.forename: C
authors.initials: C
authors.lastname: Russo
authors.forename: A
authors.initials: A
authors.lastname: Carroll
authors.forename: S
authors.initials: S
authors.lastname: Kohler
authors.forename: M
authors.initials: M
authors.lastname: Borowitz
authors.forename: M
authors.initials: M
authors.lastname: Amylon
authors.forename: A
authors.initials: A
authors.lastname: Homans
authors.forename: A
authors.initials: A
authors.lastname: Kedar
authors.forename: J
authors.initials: J
authors.lastname: Shuster
authors.forename: V
authors.initials: V
authors.lastname: Land
authors.forename: W
authors.initials: W
authors.lastname: Crist
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001483:Base Sequence; D002648:Child; D002897:Chromosomes, Human, Pair 7; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008969:Molecular Sequence Data; D009006:Monosomy; D009841:Oligonucleotides / Q000737:chemistry; D010677:Philadelphia Chromosome; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D015703:Antigens, CD; D009841:Oligonucleotides