title: Sex chromosome loss may represent a disease-associated clonal population in chronic lymphocytic leukemia.
abstract: Whether sex chromosome loss (SCL) is an age-related phenomenon or a cytogenetic marker of hematological disease is unclear. To address this issue in chronic lymphocytic leukemia (CLL), we investigated 20 cases with X or Y chromosome loss detected by conventional cytogenetics (CC). The frequency of SCL was low in CLL (2.3%). It was the sole abnormality, as detected by CC, in 10/20 (50%) patients. Fluorescence in situ hybridization (FISH) analyses confirmed SCL in all patients tested, present in 5-88% of cells (median: 68%). Deletions of 13q were observed by FISH in 16/20 (80%) patients. Compared with CLL without SCL, SCL was significantly associated with 13q deletion, especially when bi-allelic (P = 0.04). Co-hybridization analyses showed that SCL could be a concomitant, primary or secondary change, or be present in an independent clone. FISH analyses were performed on blood sub-populations isolated by Ficoll or flow cytometry. Comparing mononuclear cells (including CLL cells) and polynuclear cells separated by Ficoll, a maximum of 2% of polynuclear cells were found with SCL, whereas mononuclear cells exhibited a significantly higher loss frequency (range: 6-87%) (P = 0.03). Comparing B-cells (including CLL cells) and T-cells sorted by flow cytometry, the proportion of B-CD19+ cells with SCL was significantly higher (range: 88-96%) than that observed in T-CD3+ cells (range: 2-6%) (P = 0.008). We conclude that SCL has to be considered as a clonal aberration in CLL that may participate in the oncogenic process.
authors.affiliation: Service d'Hématologie Biologique, Hôpital Pitié-Salpêtrière, Paris, France; INSERM U872, Centre de Recherche des Cordeliers, Paris, 6, France; UPMC, Paris, 6, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Chapiro
authors.forename: Ileana
authors.initials: I
authors.lastname: Antony-Debre
authors.forename: Nathalie
authors.initials: N
authors.lastname: Marchay
authors.forename: Christophe
authors.initials: C
authors.lastname: Parizot
authors.forename: Claude
authors.initials: C
authors.lastname: Lesty
authors.forename: Hong-Anh
authors.initials: HA
authors.lastname: Cung
authors.forename: Stephanie
authors.initials: S
authors.lastname: Mathis
authors.forename: Aurore
authors.initials: A
authors.lastname: Grelier
authors.forename: Karim
authors.initials: K
authors.lastname: Maloum
authors.forename: Sylvain
authors.initials: S
authors.lastname: Choquet
authors.forename: Zahia
authors.initials: Z
authors.lastname: Azgui
authors.forename: Madalina
authors.initials: M
authors.lastname: Uzunov
authors.forename: Veronique
authors.initials: V
authors.lastname: Leblond
authors.forename: Helene
authors.initials: H
authors.lastname: Merle-Beral
authors.forename: Laurent
authors.initials: L
authors.lastname: Sutton
authors.forename: Frederic
authors.initials: F
authors.lastname: Davi
authors.forename: Florence
authors.initials: F
authors.lastname: Nguyen-Khac
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics*; D041322:Chromosomes, Human, Y / Q000235:genetics*; D002999:Clone Cells; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D016131:Lymphocyte Subsets / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012729:Sex Chromosome Aberrations