Correlation of chromosome abnormalities with laboratory features and clinical course in B‐cell chronic lymphocytic leukaemia

Oscier, David; Stevens, Janice R.; Hamblin, Terry J.; Pickering, RM; Lambert, R. De; Fitchett, M.

doi:10.1111/j.1365-2141.1990.tb06367.x

Cited by 68 publications

(45 citation statements)

References 10 publications

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“…5,15,13 An association was found between 6qÀ and a high white blood cell (WBC) count, more extensive adenopathy at presentation 15 and shorter treatment-free interval (TFI). 18 The latter finding, however, was not confirmed in another study, 16 showing no difference in terms of clinical behavior between CLL with and without 6qÀ.…”

Section: Introductionmentioning

confidence: 42%

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Chronic lymphocytic leukemia with 6q− shows distinct hematological features and intermediate prognosis

et al. 2003

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Cytogenetic and fluorescence in situ hybridization studies were successfully performed in 217 chronic lymphocytic leukemia (CLL). In all, 13 patients with 6q21 deletion were identified and characterized in comparison with 92 patients with 'favourable' karyotype (normal or 13qÀ), 69 cases with 'intermediate risk'(1-2 anomalies) and 43 cases with 'unfavourable' karyotype (complex, 11qÀ or 17pÀ). Six out of 13 cases with 6qÀ showed an excess of atypical lymphocytes, a finding confirmed at the histologic level; 420% CD38 þ cells were seen in 5/6 cases. IGVH mutational status revealed 498% homology to the germline sequence in 4/10 cases. When compared with the 'favourable' group, patients with 6qÀ showed a higher white blood cell (WBC) count, frequent splenomegaly, atypical morphology, CD38 þ and short time from diagnosis to first treatment and short survival. A higher median WBC count was found in the 6qÀ group vs the intermediate-risk group; survival was shorter in the unfavourable group. To ascertain if the 6qÀ anomaly was an independent factor predicting for an inferior outcome among those patients with 'favourable' cytogenetics, we performed an analysis of prognostic factors in 105 patients (92 'favourable' plus 13 with 6qÀ), showing that the 6qÀ chromosome maintained its prognostic significance at multivariate analysis (P ¼ 0.02) along with stage (P ¼ 0.01). We conclude that CLL with 6qÀ is characterized by a high incidence of atypical morphology, classical immunophenotype with CD38 positivity and intermediate incidence of IGVH somatic hypermutation. Clinicobiological features and outcome show that this cytogenetic subset of CLL should be allocated in an intermediate-risk category.

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Section: Introductionmentioning

confidence: 42%

“…When comparing the 6qÀ group with other CLL cases, a significant difference was only found in the initial WBC count and in the frequency of atypical morphology, as suggested previously. 16,18 In addition, we were able to document an association between CD38 positivity and 6qÀ in 117 assessable cases.…”

Section: The 6qà Is Associated With Intermediate Prognosismentioning

confidence: 80%

Chronic lymphocytic leukemia with 6q− shows distinct hematological features and intermediate prognosis

et al. 2003

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“…Whang-Peng et al 11 found an association between 6q deletions and shorter survival in NHL without the translocation t(14;18). Oscier et al 12 in their single center chromosome banding analysis found a shorter treatment-free survival for B-CLL patients with abnormalities involving 6q. However, in the large multicenter banding study compiled by the IWCCLL no adverse prognostic effect of 6q deletions was found.…”

Section: Introductionmentioning

confidence: 99%

Incidence and clinical significance of 6q deletions in B cell chronic lymphocytic leukemia

et al. 1999

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Deletions affecting the long arm of chromosome 6 (6q) are among the most commonly observed chromosomal aberrations in lymphoid malignancies and have been identified as adverse prognostic factor in subsets of tumors. Whereas at least two regions of minimal deletion have been established, one in 6q21-q23 and another in 6q25-q27, no tumor suppressor gene that might be involved in the pathogenesis of lymphoid malignancies has been so far identified from these segments. For B cell chronic lymphocytic leukemia (B-CLL) conflicting data have been reported regarding the incidence and prognostic significance of 6q deletions. In the current study we have used two YAC clones mapping to deletion regions in bands 6q21 and 6q27 as probes for fluorescence in situ hybridization (FISH) in a large series of B-CLL cases to analyze the incidence, localization and clinical significance of 6q aberrations. Among 285 patients with B-CLL studied we identified 21 cases (7%) with 6q deletions. All deletions were found with the probe mapping to 6q21 while the 6q27 region was deleted only in a third of these cases. Analysis of the clinical characteristics and laboratory parameters showed that the patients with 6q deletions had higher white blood cell counts and more extensive lymphadenopathy. However, the overall survival and the treatmentfree intervals were similar in the two groups. We conclude that deletions in 6q21 occur in 7% of B-CLL and identify a subgroup of patients characterized by a larger tumor mass but no inferior outcome.

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“…1,2 In several studies, the presence of trisomy 12 has been shown to be associated with a more aggressive clinical course. 1,[3][4][5] The role of genes potentially involved in the pathogenesis of CLL with trisomy 12 is not established. While the critical region of most aberrations in CLL could be narrowed down to a set of candidate genes, this has been difficult in the case of trisomy 12.…”

Section: Introductionmentioning

confidence: 99%

“…Earlier studies indicated that the bands 12q13-q15 comprise the minimally gained region. 3,[6][7][8] Recent RNA expression analyses showed an overexpression of genes located to chromosome 12 in CLL cases with trisomy 12 as compared to cases without this aberration. 9,10 The aim of the current study was to characterize the protein expression patterns of chromosome 12 candidate genes with oncogenic potential or functional relevance in apoptosis, cell cycle, signal transduction or somatic hypermutation (for details see Table 1) when comparing CLL cases with or without trisomy 12, CD19 þ -Bcells from healthy donors and lymphoma cell lines (JVM-2, EHEB and JURKAT).…”

Section: Introductionmentioning

confidence: 99%

Protein expression analysis of chromosome 12 candidate genes in chronic lymphocytic leukemia (CLL)

et al. 2005

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The pathogenic role of trisomy 12 in chronic lymphocytic leukemia (CLL) remains unresolved, but recently an upregulated RNA expression level has been observed for chromosome 12 candidate genes. In the current study, the protein expression of chromosome 12 candidate genes was characterized by comparing CLL cases with (n ¼ 58) or without (n ¼ 16) trisomy 12, CD19 þ -B-cells and cell lines (JVM-2, EHEB, JURKAT). Immunoblotting was performed to quantify the levels of AID, APAF-1, ARF3, CCND2, CDK2, CKD4, GLI, MDM-2, p27, Smac/ DIABLO and STAT6 (signal transducer and activator of transcription 6). The cell lines showed distinct expression patterns for CCND2, MDM-2, p27, Smac/DIABLO and STAT6, and displayed higher levels of CDK2 and CDK4 than the CLL cases. JURKAT and the CLL cases expressed uniformly high levels of p27, but low levels of CCND2. AID expression in the CLL cases was weak with slight variations regardless of the subgroup affiliation. The expression of the investigated proteins was independent of the trisomy 12 status as well as of the VH mutation status. The comparison of CD19 þ -B-cells with CLL revealed higher protein levels in CLL for CDK4, p27, Smac/ DIABLO and STAT6. Further studies including protein expression experiments in genetic high-risk subgroups of CLL have to elucidate whether these proteins qualify as candidates for targeted CLL therapies.

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Correlation of chromosome abnormalities with laboratory features and clinical course in B‐cell chronic lymphocytic leukaemia

Cited by 68 publications

References 10 publications

Chronic lymphocytic leukemia with 6q− shows distinct hematological features and intermediate prognosis

Chronic lymphocytic leukemia with 6q− shows distinct hematological features and intermediate prognosis

Incidence and clinical significance of 6q deletions in B cell chronic lymphocytic leukemia

Protein expression analysis of chromosome 12 candidate genes in chronic lymphocytic leukemia (CLL)

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