Chromosome abnormalities of leukaemic B lymphocytes in chronic lymphocytic leukaemia

Hurley, John N.; Fu, Shu Man; Kunkel, Henry G.; Chaganti, R. S. K.; German, James

doi:10.1038/283076a0

Cited by 55 publications

(13 citation statements)

References 8 publications

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“…The initial observations of recurrent chromosome aberrations in CLL were not reported before the late 1970s and early 1980s, and the first abnormality consistently described as a recurrent aberration in CLL was trisomy 12 (2)(3)(4)(5)(6)22). Gahrton et al (5,6) initially observed trisomy 12 as a clonal aberration in 5 of 11 CLL cases studied.…”

Section: Chromosome Banding Studiesmentioning

confidence: 99%

Genetic Features of B‐Cell Chronic Lymphocytic Leukemia

Stilgenbauer

Lichter

Döhner

2000

Rev Clin Exp Hematol

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The genetic features of B-cell chronic lymphocytic leukemia (CLL) are currently being reassessed by molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH). Conventional cytogenetic studies by chromosome banding are difficult in CLL mainly because of the low in vitro mitotic activity of the tumor cells, which leads to poor quantity and quality of metaphase spreads. Molecular genetic analyses are limited because candidate genes are known for only a few chromosomal aberrations that are observed in CLL. FISH was found to be a powerful tool for the genetic analysis of CLL as it overcomes both the low mitotic activity of the CLL cells and the lack of suitable candidate genes for analysis. Using FISH, the detection of chromosomal aberrations can be performed at the single cell level in both dividing and non-dividing cells, thus circumventing the need of metaphase preparations from tumor cells. Probes for the detection of trisomies, deletions and translocation breakpoints can be applied to the regions of interest with the growing number of clones available from genome-wide libraries. Using the interphase cytogenetic FISH approach with a disease specific set of probes, chromosome aberrations can be found in more than 80% of CLL cases. The most frequently observed abnormalities are losses of chromosomal material, with deletions in band 13q14 being the most common, followed by deletions in 11q22-q23, deletions in 17p13 and deletions in 6q21. The most common gains of chromosomal material are trisomies 12q, 8q and 3q. Translocation breakpoints, in particular involving the immunoglobulin heavy chain locus at 14q32, which are frequently observed in other types of non-Hodgkin's lymphoma, are rare events in CLL. Genes affected by common chromosome aberrations in CLL appear to be p53 in cases with 17p deletion and ataxia telangiectasia mutated (ATM), which is mutated in a subset of cases with 11q22-q23 aberrations. However, for the other frequently affected genomic regions, the search for candidate genes is ongoing. In parallel, the accurate evaluation of the incidence of chromosome aberrations in CLL by FISH allows the correlation of genetic abnormalities with clinical disease manifestations and outcome. In particular, 17p abnormalities and deletions in 11q22-q23 have already been shown to be among the most important independent prognostic factors identifying subgroups of patients with rapid disease progression and short survival. In addition, deletion 17p has been associated with resistance to treatment with purine analogs. Therefore, genetic abnormalities may allow a risk assessment for individual patients at the time of diagnosis, thus giving the opportunity for a risk-adapted management.

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Section: Chromosome Banding Studiesmentioning

confidence: 99%

Genetic Features of B‐Cell Chronic Lymphocytic Leukemia

Stilgenbauer

Lichter

Döhner

2000

Rev Clin Exp Hematol

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“…Trisomy 12 is correlated with atypical morphology and shortened survival (worse prognosis) (24, 25). Conventional cytogenetic methods can detect 40-50% abnormalities in B-CLL patients (26, 27), while using fluorescent in situ hybridization (FISH) has brought the sensitivity of cytogenetic analysis to a higher level, by which, 80% of abnormalities can be detected (28). In the previous study, we analyzed the correlation of del (13q), del (11q) and trisomy 12 with features of B-CLL in Iranian cases (29).…”

Section: Introductionmentioning

confidence: 99%

FISH Analysis for del6q21 and del17p13 in B-cell Chronic Lymphocytic Leukemia in Iranians

Teimori

Ashoori

Akbari

et al. 2013

Iran Red Crescent Med J

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BackgroundB-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in the Western world. Major progress has been made in assessing typical chromosomal abnormalities and recognition of the correlation of these chromosomal abnormalities with laboratory features and clinical course of the disease. The most frequent genomic changes are deletions at 13q14, 11q22-23 and 17p13 and trisomy of chromosome 12.ObjectivesThe aim of this study was to investigate the frequency of chromosomal aberrations in B-CLL patients’ peripheral blood and/or bone marrow using a molecular cytogenetic method, interphase fluorescence in situ hybridization (I-FISH) and to evaluate the correlation between these genomic changes and clinical findings.Patients and MethodsI-FISH analyses were performed on bone marrow and blood samples of 66 B-CLL patients.ResultsDeletion of 17p13 was found in 11 (16.6%) and deletion 6q21 was present in 5 (7.5%). Statistical analyses were performed to investigate the correlation of these molecular-cytogenetic findings with family history, Rai staging and CD38 marker. No clear differences in distribution was noted for del17p13 and del6q21 among patients with and without family history, and no direct correlation was noted between these genomic changes and CD38 marker, but the correlation of del17p13 and Rai stage was significant. There was a high frequency of Rai stage II within del17p13 patients.ConclusionsIt was demonstrated that the presence of del6q21 in B-CLL patients indicates poor prognosis and on the contrary, presence of del17p13 points at the good prognostic value of the disease.

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“…Although no common genetic alteration has been found in CLL, several known recurrent aberrations have been identified, i.e., deletions of chromosomes 11q, 13q, and 17p, and trisomy 12, which were discovered by conventional cytogenetic banding techniques during the 1980s [23][24][25]. However, due to the moderate proliferation rate of CLL cells in vitro, early karyotyping studies were limited in their ability to detect aberrations.…”

Section: Genomic Aberrations In Cllmentioning

confidence: 99%

New insights into the pathobiology of chronic lymphocytic leukemia

Gunnarsson

Rosenquist

2011

J Hematopathol

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Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a varying clinical outcome; however, the pathogenic mechanisms involved in disease development have remained largely unknown. In recent years, novel biomarkers, such as certain recurrent genomic alterations and the immunoglobulin heavy variable gene mutational status, have significantly improved the subdivision of the disease along with the prognostic assessment of individual patients. Advanced molecular studies have also revealed important genetic/epigenetic events and potential susceptibility loci for CLL, as well as implicating antigens in CLL development. Furthermore, the presence of monoclonal B cell lymphocytosis (MBL) has been demonstrated to precede CLL and appears to be a pre-leukemic condition. In this review, we will not only focus on recent developments made in the fields of genetics and immunogenetics in CLL, but also provide a brief overview of MBL, since we believe that advancements in these areas will have a major impact on our understanding of CLL pathobiology.

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Chromosome abnormalities of leukaemic B lymphocytes in chronic lymphocytic leukaemia

Cited by 55 publications

References 8 publications

Genetic Features of B‐Cell Chronic Lymphocytic Leukemia

Genetic Features of B‐Cell Chronic Lymphocytic Leukemia

FISH Analysis for del6q21 and del17p13 in B-cell Chronic Lymphocytic Leukemia in Iranians

New insights into the pathobiology of chronic lymphocytic leukemia

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