title: Cryptic deletion involving the ATM locus at 11q22.3 approximately q23.1 in B-cell chronic lymphocytic leukemia and related disorders.
abstract: B-cell chronic lymphocytic leukemia (B-CLL) follows a heterogeneous clinical course, and several biological parameters have been investigated to try to predict its clinical outcome. New staging systems including cytogenetics and CD38 expression as predictive values have been developed. Deletions of 11q22.3 approximately q23.1 detected at diagnosis in cases of CLL patients have been associated with a relatively aggressive disease. This region, which contains the ataxia telangiectasia mutated (ATM) locus, may be implicated in the pathogenesis of lymphoid malignancies. We developed a set of dual-color specific probes to evaluate the ATM deletion by means of fluorescence in situ hybridization (FISH). We also used flow cytometry to investigate CD38 expression. Forty-one patients with CLL or low-grade B-cell lymphomas were studied at diagnosis or before treatment. FISH showed that only three CLL patients had deletions in the 11q23 locus; all three had progressive disease and were resistant to treatment. These data show that our FISH set of probes efficiently detects ATM deletions in CLL. No correlation was found between ATM deletions and CD38 expression level. These results confirm the prognostic significance of ATM deletions in CLL.
authors.affiliation: Laboratoire d'Hématologie, Unité Fonctionelle d'Hématologie, Hôpital Jean Verdier, Avenue du 14 Juillet, 93145 Bondy Cedex, France. virginie.eclache@jvr.ap-hop-paris.fr
authors.forename: Virginie
authors.initials: V
authors.lastname: Eclache
authors.forename: Sylvie
authors.initials: S
authors.lastname: Caulet-Maugendre
authors.forename: Hélène A
authors.initials: HA
authors.lastname: Poirel
authors.forename: Mohand
authors.initials: M
authors.lastname: Djemai
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Robert
authors.forename: Françoise
authors.initials: F
authors.lastname: Lejeune
authors.forename: Martine
authors.initials: M
authors.lastname: Raphaël
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000378:metabolism; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001260:Ataxia Telangiectasia / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004268:DNA-Binding Proteins; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D015463:Leukemia, Prolymphocytic / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008223:Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D015703:Antigens, CD; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1