title: Fluorescent in situ hybridization and cytogenetic studies of trisomy 12 in chronic lymphocytic leukemia.
abstract: Cytogenetic studies (CG) of 475 chronic lymphocytic leukemia (CLL) cases showed trisomy 12 in 6.1% or 26% of patients with abnormal karyotypes. Fluorescence in situ hybridization (FISH) detected trisomy 12 in 35% of 117 CLL patients. Only 34.6% of cases detected by FISH were detected by CG. Twelve patients had low levels of trisomic cells (4% to 11%) relative to clonal B cells (47.5% to 86%), suggestive of clonal evolution. Untreated patients with trisomy 12 were predominantly male (P < .05) and had an increased incidence of splenomegaly (P < .03). Patients with trisomy 12 were more likely to be previously treated and had advanced Binet stage compared with those without trisomy 12. The median survival was shorter in patients with trisomy 12 (7.8 years) and patients with other chromosomal abnormalities without trisomy 12 by FISH (5.5 years) than in patients with diploid karyotypes (14.4 years). The response to fludarabine was similar to that of patients with diploid karyotypes, but there was a trend for earlier disease progression. FISH detected residual disease in all patients with trisomy 12 in complete (n = 6) or partial remission (n = 4). As few as 1 trisomic cell in 5,000 was detected by performing FISH on fluorescence-activated cell sorter-sorted cells. Trisomy 12 was absent in T cells in patients with trisomy 12. We conclude that FISH identifies trisomy 12 approximately 2.6 times more often than CG, readily identifies minimal residual disease, and predicts for a shorter median survival.
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Department of Hematology, Houston 77030.
authors.forename: S M
authors.initials: SM
authors.lastname: Escudier
authors.forename: J M
authors.initials: JM
authors.lastname: Pereira-Leahy
authors.forename: J W
authors.initials: JW
authors.lastname: Drach
authors.forename: H U
authors.initials: HU
authors.lastname: Weier
authors.forename: A M
authors.initials: AM
authors.lastname: Goodacre
authors.forename: M A
authors.initials: MA
authors.lastname: Cork
authors.forename: J M
authors.initials: JM
authors.lastname: Trujillo
authors.forename: M J
authors.initials: MJ
authors.lastname: Keating
authors.forename: M
authors.initials: M
authors.lastname: Andreeff
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology; D002881:Chromosomes, Human, Pair 12; D006801:Humans; D017403:In Situ Hybridization; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008677:Metaphase; D009000:Monocytes / Q000473:pathology / Q000502:physiology; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D014314:Trisomy
chemical_list: D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte