title: Trisomy 12 defines a group of CLL with atypical morphology: correlation between cytogenetic, clinical and laboratory features in 544 patients.
abstract: We have analysed the clinical and laboratory features in 544 patients with chronic lymphocytic leukaemia (CLL) with available cytogenetics and fluorescence in-situ hybridization (FISH) analysis for trisomy 12 in half of them, to examine the correlation between chromosome abnormalities and clinical or laboratory parameters. Five chromosome groups were defined: (1) trisomy 12 (18%), detected as the sole abnormality or associated with other changes; (2) del(13)(q12-14) (7%); (3) other abnormal karyotypes (20%); (4) normal karyotype (41%); and (5) no divisions (14%). There were no differences in the age distribution between the five groups. Clinical stages (Binet) were: A (74%), B (12%) and C (14%). Stage A was common in cases with del(13q)(82%), normal (84%) and other abnormal karyotypes (74%), whereas it was less common in trisomy 12 cases (64%) and those with no divisions (48%). Typical CLL morphology was found in 83% of cases; 10% had more than 10% prolymphocytes (CLL/PL) and 7% had other atypical features. CLL with trisomy 12 was the only group with a high frequency of either CLL/PL (31%) or atypical morphology (24%). Atypical morphology and CLL/PL were even more frequent when trisomy 12 was associated with other chromosomal abnormalities (70% v 46%). The incidence of cases with CLL/PL and other atypical morphology was significantly lower in the other chromosome groups (P < 0.001). There were no differences in immunophenotype among the various groups except for a higher frequency of stronger Smlg and FMC7 expression in cases with trisomy 12, particularly those with CLL/PL and other atypical morphology. Our findings confirm that trisomy 12 defines a subgroup of CLL with more frequent atypical morphology, including CLL/PL, stronger SmIg and FMC7 expression, more advanced stages (B and C in 18%) and possibly worse prognosis.
authors.affiliation: Academic Department of Haematology and Cytogenetics, Royal Marsden Hospital, London.
authors.forename: E
authors.initials: E
authors.lastname: Matutes
authors.forename: D
authors.initials: D
authors.lastname: Oscier
authors.forename: J
authors.initials: J
authors.lastname: Garcia-Marco
authors.forename: J
authors.initials: J
authors.lastname: Ellis
authors.forename: A
authors.initials: A
authors.lastname: Copplestone
authors.forename: R
authors.initials: R
authors.lastname: Gillingham
authors.forename: T
authors.initials: T
authors.lastname: Hamblin
authors.forename: D
authors.initials: D
authors.lastname: Lens
authors.forename: G J
authors.initials: GJ
authors.lastname: Swansbury
authors.forename: D
authors.initials: D
authors.lastname: Catovsky
mesh_terms: D000368:Aged; D002881:Chromosomes, Human, Pair 12; D005260:Female; D017353:Gene Deletion; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014314:Trisomy