Further characterization of morphologically defined typical and atypical CLL: a clinical, immunophenotypic, cytogenetic and prognostic study on 390 cases (original) (raw)
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Blood, 2003
disease show distinctive phenotypic and genotypic features Chronic lymphocytic leukemia patients with highly stable and indolent http://bloodjournal.hematologylibrary.org/content/102/3/1035.full.html Updated information and services can be found at: (4217 articles) Neoplasia (5012 articles) Immunobiology (3712 articles) Clinical Trials and Observations Articles on similar topics can be found in the following Blood collections http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub\_requests
Characteristic chromosome abnormalities in patients with chronic lymphocytic leukemia (CLL) have been shown to provide important prognostic information. Karyotyping and Fluorescence in situ hybridization (FISH) currently used in clinical diagnostics of CLL are targeted tests aimed at specific Cytogenetic marker. The aim of this study was to understand the role of the Cytogenetics and molecular Cytogenetic markers in Chronic Lymphocytic Leukemia through Cytogenetics techniques, i.e. Conventional Cytogenetics and FISH in a clinical diagnostic setting. Karyotyping and FISH were performed in all 15 CLL patients and compared with international prognostic scoring criteria. Here, we conclude that the clinical significance of cytogenetic examination in CLL is apparent. That most of patients with CLL show clonal Chromosomal aberrations (CAs) has become clearer with the ongoing approach of more sensitive detection methods. In CLL, there is a positive relationship between the presence of CAs and progressive disease, showing a prognostic role for cytogenetic investigations. The prognostic relevance of these Cytogenetics alterations requires further evaluation in prospective of targeted therapy.
Structural alterations in chronic lymphocytic leukaemia. Cytogenetic and FISH analysis
Hematological Oncology, 2013
In this study, we described cytogenetics and fluorescence in situ hybridization (FISH) analysis performed in chronic lymphocytic leukaemia (CLL) patients with structural alterations. Results were correlated with clinical characteristics. A total of 38 CLL patients: 16 cases with complex and 22 with simple karyotypes were studied. For comparison of clinical parameters, a control group of 78 CLL patients with normal karyotype and without FISH genomic alterations were also evaluated. We found 38 structural abnormalities not previously described in the literature, 28 (74%) of them were translocations. In cases with complex karyotypes, chromosomes 6, 8 and 13 were the most frequently involved in new alterations (nine each), followed by chromosomes 12, 14 and 15 (six each). Chromosome 8p was particularly involved in losses, being 8p21-pter the commonest region of overlap. Cases with simple karyotypes, showed del(6q) as the most frequent alteration (39%). Del(9)(q11) was recurrent in our series. Analysis of clinical parameters showed significant differences in white blood count (p = 0.005) and platelet count (p = 0.015) between patients with structural alterations and the control group. In addition, patients with structural alterations had a significantly shorter time to first treatment (TFT) (29 months) than the control group (69 months) (p = 0.037). Cases with complex karyotypes had a lower proportion of patients in Rai 0 clinical stage (15.4% vs 75%) (p = 0.005) and higher b 2 microglobulin levels (3.3 vs 2.5 mg/mL) (p = 0.037) than those with simple karyotypes. Furthermore, a shorter TFT (13 months) and overall survival (56 months) in the complex karyotypes group compared with controls (69 and 144 months, respectively) (p = 0.015 and p = 0.005, respectively) were also found. Our results support the importance of cytogenetic analysis for clinical outcome in CLL and suggest that the diversity of genomic alterations is much greater than previously appreciated.
Neoplasma, 2011
We evaluated the prognostic impact of chromosomal abnormalities as detected by interphase fluorescence in situ hybridization (iFISH) in 86 chronic lymphocytic leukemia (CLL) patients. Overall, 39 of 86 (45%) patients displayed one (35%) or more (10%) chromosomal abnormalities, del13q (31%) being more frequently detected than trisomy 12 (19%) followed by del11q (17%), del17p (6%) and del6q (5%). Significant differences in the treatment free intervals (TFIs) were observed among individual cytogenetic subgroups (p=0.027) with the shortest mean TFIs in subgroups with del17p, del11q and trisomy 12 (10, 12 and 14 months, respectively) as compared to subgroups with normal cytogenetics (38 months) and del13q (68 months). Poor response to therapy was observed in subgroups with del11q (p=0.044) and trisomy 12 (p=0.047) while patients with normal cytogenetics had good response (p=0.003). Furthermore, del17p and del11q were associated with highest tumor burden and disease activity as reflected by corresponding laboratory data.
Cancer genetics
Pretherapy patients with chronic lymphocytic leukemia (CLL) from US Intergroup trial E2997 were analyzed with single nucleotide polymorphism microarrays to detect acquired chromosomal anomalies. The four CLL-typical anomalies (11q-, รพ12, 13q-, and 17p-) were found at expected frequencies. Acquired anomalies in other regions account for 70% of the total detected anomalies, and their number per participant has a significant effect on progression-free survival after adjusting for the effects of 17p-(and other covariates). These results were compared with those from a previous study of more than 50,000 participants from the GENEVA consortium of genomewide association studies, which analyzed individuals with a variety of medical conditions and healthy controls. The percentage of individuals with acquired anomalies is vastly different between the two studies (GENEVA 0.8%; E2997 80%). The composition of the anomalies also differs, with GENEVA having a higher percentage of acquired uniparental disomies and a lower percentage of deletions. The four common CLL anomalies are among the most frequent in GENEVA participants, some of whom may have CLL-precursor conditions or early stages of CLL. However, the patients from E2997 (and other studies of symptomatic CLL) have recurrent acquired anomalies that were not found in GENEVA participants, thus identifying genomic changes that may be unique to symptomatic stages of CLL.
Trisomy 12 is uncommon in typical chronic lymphocytic leukaemias
British Journal of Haematology, 1994
The incidence of trisomy 12 was studied by conventional chromosome analysis in 11 1 patients referred as B-cell chronic lymphocytic leukaemia (B-CLL). Fluorescent in situ hybridization (FISH) was also applied in 34 of those patients with either a normal karyotype or no analysable mitoses. By karyotyping, trisomy 12 was present in 11'7% (1 3/111), whereas additional FISH increased the incidence to 14.4% (16/111). When subdividing our cases in either typical CLL (n = go), fulfilling the FAB classification criteria, or atypical CLL (n = 21). with one or more variations from those criteria, the incidence of t 1 2 by metaphase analysis was 3% and 48%. respectively. Additional FISH increased the incidence to 4% and 57%. The most common aberration in atypical CLL was FMC7 positivity (n = 11). followed by CD5 negativity (n = 8), strong surface immunoglobulin staining (n = 7 ) and atypical morphology (n = 6). Trisomy 12 could only be demonstrated in a small proportion of neoplastic cells in all positive cases. By FISH and/or karyotyping, all available samples at diagnosis of the disease were positive.