Interphase fluorescence in situ hybridization analysis of del(11)(q23) and del(17)(p13) in chronic lymphocytic leukemia. a study of 40 early-onset patients.
Although B-cell chronic lymphocytic leukemia (B-CLL) is the most common form of leukemia in Western countries, little is known about its underlying molecular abnormalities and their prognostic significance, particularly for use in early therapeutic interventions in young patients. As TP53 tumor suppressor gene abnormalities and 11q23 deletions are reported to be prognostically adverse in hematologic malignancies, we used interphase fluorescence in situ hybridization to analyze their incidence and prognostic significance in young B-CLL patients. Bone marrow samples from 40 untreated B-CLL patients at diagnosis were studied using five yeast artificial chromosome clones from the 11q23.1 approximately q23.3 chromosomal region and a probe specific for the 17p13.1 locus. Twenty-three patients (58%) carried 11q deletions. Interestingly, 16 of 17 patients (94%) who showed early disease progression exhibited this chromosomal abnormality, suggesting that 11q deletions may help to identify more aggressive disease in early stage patients. In contrast, monoallelic TP53 deletions were found in all of the patients. The TP53 and 11q deletions were only present in a proportion of the clonal B-cells, which suggests that they are secondary events in B-CLL.
Doneda
Luisa
L
Department of Biology and Genetics Medical Faculty, University of Milan, Milan, Italy. lidia.larrizza@unimi.it
Montillo
Marco
M
Intropido
Liliana
L
Tedeschi
Alessandra
A
Morra
Enrica
E
Larizza
Lidia
L
D000328:Adult; D017668:Age of Onset; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000648:ultrastructure; D001853:Bone Marrow / Q000473:pathology; D002872:Chromosome Deletion; D018244:Chromosomes, Artificial, Yeast; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics / Q000648:ultrastructure*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics / Q000648:ultrastructure*; D002999:Clone Cells / Q000648:ultrastructure; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007399:Interphase; D007558:Italy / Q000453:epidemiology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000648:ultrastructure; D011379:Prognosis