title: Prognostic significance of additional chromosome abnormalities in adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia.
abstract: The clinical and biological significance of additional chromosome aberrations was investigated in a large series of 66 adult patients with Philadelphia (Ph) chromosome positive acute lymphoblastic leukaemia (ALL). Additional chromosome changes were observed in 71% of the cases. 9p abnormalities were identified in 26%, and monosomy 7 as well as hyperdiploid karyotypes 50 were both found in 17% of cases. 9p anomalies were characterized by a low complete remission (CR) rate (58%) and an extremely short median remission duration (MRD: 100 d). In patients with monosomy 7, the poor treatment outcome was confirmed (CR rate 55%: MRD 113 d). In contrast, all patients with hyperdiploid karyotypes 50 achieved CR, and the overall survival was superior to all other Ph-positive ALL patients except those without additional chromosome aberrations. Exclusive rearrangement of the minor breakpoint cluster region of the BCR gene and lack of coexpression of myeloid-associated antigens in cases with 9p anomalies as well as a high frequency of rearrangements of the major breakpoint cluster region of the BCR gene in patients with monosomy 7 (89%) further substantiated that additional chromosome aberrations may characterize distinct subgroups of Ph-positive ALL. Moreover, the necessity of the complementing use of chromosome banding analyses, polymerase chain reaction (PCR) assays, and fluorescence in situ hybridizations in the accurate identification of Ph-positive patients has become evident due to variant Ph translocations in 3%, and negative PCR assays in 4% of the cases.
authors.affiliation: Department of Clinical Genetics, Medical Centre of Human Genetics, Philipps University, Marburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Rieder
authors.forename: W D
authors.initials: WD
authors.lastname: Ludwig
authors.forename: W
authors.initials: W
authors.lastname: Gassmann
authors.forename: J
authors.initials: J
authors.lastname: Maurer
authors.forename: J W
authors.initials: JW
authors.lastname: Janssen
authors.forename: N
authors.initials: N
authors.lastname: Gökbuget
authors.forename: S
authors.initials: S
authors.lastname: Schwartz
authors.forename: E
authors.initials: E
authors.lastname: Thiel
authors.forename: H
authors.initials: H
authors.lastname: Löffler
authors.forename: C R
authors.initials: CR
authors.lastname: Bartram
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
authors.forename: C
authors.initials: C
authors.lastname: Fonatsch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D015321:Gene Rearrangement; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000628:therapy; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome