Haematologica · 2002
Late appearance of the 11q22.3-23.1 deletion involving the ATM locus in B-cell chronic lymphocytic leukemia and related disorders. Clinico-biological significance.
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Cuneo Antonio, Bigoni Renato, Rigolin Gian Matteo, Roberti Maria Grazia, Bardi Antonella, Cavazzini Francesco, Milani Raffaella, Minotto Claudia, Tieghi Alessia, Della Porta Matteo, Agostini Paola, Tammiso Elisa, Negrini Massimo, Castoldi Gianluigi
Аннотация
BACKGROUND AND OBJECTIVES: Chromosome 11q22.3-23.1 deletions involving the ataxia-teleangiectasia mutated (ATM) locus (11q-/ATM+/-) are detected at diagnosis in 10-20% of cases of B-cell chronic lymphocytic leukemia (CLL) and are associated with a relatively aggressive disease. The aim of this study was to ascertain whether 11q-/ATM+/- may appear late during the course of the disease and to analyze its possible correlation with disease evolution.
DESIGN AND METHODS: Eighty-two patients with CLL and related disorders, i.e. CLL/PL and prolymphocytic leukemia (PLL), without 11q- at diagnosis were sequentially ascertained at 1-2 year intervals by conventional cytogenetic analysis (CCA) and fluorescence in situ hybridization (FISH), using an ATM-specific probe.
RESULTS: Eight patients acquired a submicroscopic 11q deletion 13-43 months after diagnosis: the diagnosis at presentation was CLL in 3 cases, CLL/PL in 3 cases and PLL in 2 cases. A 13q14 deletion preceded the development of 11q- in four patients; additional aberrations included +12 (three cases), 17p13 deletion and 6q21 deletion (one case each). The acquisition of the 11q deletion was more frequently found in those patients presenting with CLL/PL and PLL than typical CLL (p=0.0016) and with splenomegaly (p=0.003). Follow-up data showed that karyotype evolution (p=0.009) and cytological transformation (p<0.001) were associated with the acquisition of this cytogenetic lesion. The variables predicting for a shorter survival in this series included the 11q deletion (p=0.03), along with other classical clinicobiological parameters (performance status, advanced stage, splenomegaly, elevated serum beta2 microglobulin and lactate dehydrogenase levels.
INTERPRETATION AND CONCLUSIONS: a) Submicroscopic 11q deletion involving the ATM locus may, in some instances, represent a secondary change in CLL, CLL/P and PLL, suggesting that sequential FISH analyses are necessary to detect this chromosome anomaly in some patients; b) the acquisition of 11q-/ATM deletion may play a role in determining cytological transformation and disease progression of CLL and related disorders.
DESIGN AND METHODS: Eighty-two patients with CLL and related disorders, i.e. CLL/PL and prolymphocytic leukemia (PLL), without 11q- at diagnosis were sequentially ascertained at 1-2 year intervals by conventional cytogenetic analysis (CCA) and fluorescence in situ hybridization (FISH), using an ATM-specific probe.
RESULTS: Eight patients acquired a submicroscopic 11q deletion 13-43 months after diagnosis: the diagnosis at presentation was CLL in 3 cases, CLL/PL in 3 cases and PLL in 2 cases. A 13q14 deletion preceded the development of 11q- in four patients; additional aberrations included +12 (three cases), 17p13 deletion and 6q21 deletion (one case each). The acquisition of the 11q deletion was more frequently found in those patients presenting with CLL/PL and PLL than typical CLL (p=0.0016) and with splenomegaly (p=0.003). Follow-up data showed that karyotype evolution (p=0.009) and cytological transformation (p<0.001) were associated with the acquisition of this cytogenetic lesion. The variables predicting for a shorter survival in this series included the 11q deletion (p=0.03), along with other classical clinicobiological parameters (performance status, advanced stage, splenomegaly, elevated serum beta2 microglobulin and lactate dehydrogenase levels.
INTERPRETATION AND CONCLUSIONS: a) Submicroscopic 11q deletion involving the ATM locus may, in some instances, represent a secondary change in CLL, CLL/P and PLL, suggesting that sequential FISH analyses are necessary to detect this chromosome anomaly in some patients; b) the acquisition of 11q-/ATM deletion may play a role in determining cytological transformation and disease progression of CLL and related disorders.
Предметные рубрики MeSH
AdultAgedAntineoplastic Combined Chemotherapy ProtocolsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsChromosome DeletionChromosomes, Human, Pair 11DNA-Binding ProteinsDisease ProgressionFemaleFollow-Up StudiesHumansIn Situ Hybridization, FluorescenceInterphaseKaryotypingLeukemia, Lymphocytic, Chronic, B-CellLeukemia, ProlymphocyticMaleMiddle AgedNeoplasm StagingPatient SelectionProtein Serine-Threonine KinasesSplenomegalyTumor Suppressor Proteins