Aberrations of chromosome 6 in 193 newly diagnosed untreated cases of chronic lymphocytic leukemia

Philip, Preben; Geisler, Christian H.; Hansen, Mogens; Hasselbalch, Hans Carl; Christensen, Bjarne; Drivsholm, Aage; Lund, B; Nielsen, Janni; Jensen, Kaj Bjørn; Andersen, Erik André

doi:10.1016/0165-4608(91)90112-8

Cited by 15 publications

(4 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the time intervals to clinical progression were significantly shorter in the group demonstrating temporal acquisition of 6q abnormalities ( Figure 3). This observation supports prior data that suggest a relatively poor prognosis in B-CLL patients with 6q abnormalities [16]. Our data further suggest that this poor outcome might be related to the clonal acquisition of 6q abnormalities over time, rather than the presence of these abnormalities at baseline.…”

Section: Discussionsupporting

confidence: 91%

“…Whereas no consistent pattern of clonal evolution was observed, the most common secondary chromosome abnormalities involved the long arm of chromosome 6 in the region of 6q21-q24. Structural chromosome 6 abnormalities have been described previously in B-CLL and other lymphoid malignancies [16][17][18], but they have not been documented previously as common secondarily acquired abnormalities in the karyotypic evolution of CLL. All but one of the temporally acquired 6q abnormalities arose in patients with other clonal abnormalities detectable at baseline, supporting the occurrence of clonal evolution in these cases.…”

Section: Discussionmentioning

confidence: 90%

See 1 more Smart Citation

Secondary Abnormalities of Chromosome 6q in B-Cell Chronic Lymphocytic Leukemia: A Sequential Study of Karyotypic Instability in 51 Patients

Finn

Kay²,

Kroft

et al. 1998

Am. J. Hematol.

View full text Add to dashboard Cite

Although karyotypic abnormalities are well documented in B-cell chronic lymphocytic leukemia (B-CLL), few sequential cytogenetic studies have been done. In this study, peripheral blood lymphocytes from fifty-one patients with B-CLL were sequentially karyotyped over a mean interval of 13.8 months (range, one to 51 months). Cytogenetic clones were detected in 33/51 patients (66%) on initial study, including 17 patients with structural abnormalities of chromosome 13q14, and three patients with trisomy 12. Karyotypic evolution was documented in 22/51 patients (43%). The most common secondarily acquired chromosome aberrations were structural abnormalities of the long arm of chromosome 6 involving the region of 6q21-q24 (six patients). Four patients each had acquired structural abnormalities of 1q, 3p, 12q, and 13q. Disease progression, as measured by advance in Rai stage or death from the disease, was observed more often in the clonal evolution group than in the karyotypically stable group (11/22 vs. 5/29; P = 0.017). Patients with secondary abnormalities of 6q had a significantly decreased progression-free survival interval compared with other patients in the study (P = .023). The authors conclude that clonal karyotypic evolution is common in B-CLL, and that clonal evolution correlates with clinical disease progression. Furthermore, the poor outcomes previously attributed to CLL with 6q abnormalities may be related to the clonal acquisition of these abnormalities over time. Future studies should focus on the relevant genetic events underlying the clinical progression observed with karyotypic evolution of B-CLL.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 90%

Secondary Abnormalities of Chromosome 6q in B-Cell Chronic Lymphocytic Leukemia: A Sequential Study of Karyotypic Instability in 51 Patients

Finn

Kay²,

Kroft

et al. 1998

Am. J. Hematol.

View full text Add to dashboard Cite

show abstract

“…(i) A 6p24±25 anomaly may be found in all abnormal metaphases in CLL, representing a cytogenetic defect that is frequently associated with other unbalanced chromosome lesions. The presence of this anomaly in several reports in the literature (Philip et al, 1991;Peterson et al, 1992;Geisler et al, 1997) suggests that it may be a non-random event, as is the case with 4q21 aberration, which was previously reported by Peterson et al (1992) in 4 out of 82 cases with complex karyotypes. Interestingly, a high frequency of gain of chromosome 4q material in both typical and atypical CLL was found in a recent comparative genomic hybridization study of 41 cases (O'Connor et al, 1998), suggesting that chromosome 4q abnormalities may play a role in the pathogenesis of CLL.…”

Section: Discussionmentioning

confidence: 50%

Four novel non‐random chromosome rearrangements in B‐cell chronic lymphocytic leukaemia: 6p24–25 and 12p12–13 translocations, 4q21 anomalies and monosomy 21

et al. 2000

View full text Add to dashboard Cite

Summary. Nine patients with previously unreported chromosome changes were identi®ed among 209 B-cell chronic lymphocytic leukaemia (CLL) cases: three patients had a translocation involving 6p24±25; three had a 12p12±13 translocation; two had 4q21 involvement (one with coexisting 6p anomaly); and two had monosomy 21.Interphase¯uorescence in situ hybridization (FISH) detected some cryptic aberrations (12, 6q±, 17pÀ, 11qÀ) in those patients with 6p translocations, whereas only a cytogenetically undetected 13q14 deletion was found in the remaining cases.Atypical morphology was noted in six cases, including both cases with monosomy 21, two cases with 6p and 4q21 anomaly and one case with 12p involvement. Four of these cases also had more than one phenotype deviation with respect to the classical CLL phenotype. Disease progression after 21±51 months (median 41) was noted in two cases with 6p and 4q21 involvement and in one case with 12p anomaly and monosomy 21.We arrived at the following conclusions: (i) 6p24±25 and, possibly, 4q21 lesions represent non-random events in CLL, occurring in association with other well-known unbalanced rearrangements; (ii) 12p rearrangements and monosomy 21 may possibly represent early chromosome defects that are not associated with the classical DNA gains and losses known to be present in the majority of CLL; and (iii) atypical morphology and immunophenotype as well as disease progression were frequently observed in these cases

show abstract

“…Abnormalities of chromosome 6 occur in 6–9% of patients, with additional chromosomes affected in about half (Pittman & Catovsky 1984; Juliusson et al ., 1990; Oscier et al ., 1990; Philip et al ., 1991; Gaidano et al ., 1994). As a single abnormality it appears to have no prognostic significance.…”

Section: Chromosomementioning

confidence: 99%

Molecular abnormalities in B-cell chronic lymphocytic leukaemia

Fegan¹

2001

Clinical &Amp; Laboratory Haematology

View full text Add to dashboard Cite

Chronic lymphocytic leukaemia is the commonest adult leukaemia, however the pathogenesis is largely unknown. Since the 1980s specific chromosomal abnormalities have been identified, of which the commonest are deletions of chromosomes 6q, 11q23, 13q14 and 17q13 and trisomy 12. The search for the responsible oncogenes at these sites has proved to be extremely frustrating. There are many oncogenes at 11q23 but the exact gene(s) responsible have yet to be identified. Germline abnormalities of the ATM gene occur in about 18% of patients compared to a normal population carriage of 0.5% but not all studies agree that ATM is the gene responsible. Unfortunately, despite the identification of various minimally deleted regions and the full sequencing of 13q14 no oncogenes have been identified. All original studies suggested the presence of a autosomally recessive tumour suppressor gene at this site but more recent studies suggest this may not be the case and the pathogenesis is more complex than first thought. Similarly, no genes have been identified at 6q or on chromosome 12. We know that the p53 tumour suppressor gene at 17p13 is an important prognostic indicator but it occurs in a minority of patients (about 15%), usually in patients with advanced disease, and therefore probably is not of aetiological importance.

show abstract

Aberrations of chromosome 6 in 193 newly diagnosed untreated cases of chronic lymphocytic leukemia

Cited by 15 publications

References 19 publications

Secondary Abnormalities of Chromosome 6q in B-Cell Chronic Lymphocytic Leukemia: A Sequential Study of Karyotypic Instability in 51 Patients

Secondary Abnormalities of Chromosome 6q in B-Cell Chronic Lymphocytic Leukemia: A Sequential Study of Karyotypic Instability in 51 Patients

Four novel non‐random chromosome rearrangements in B‐cell chronic lymphocytic leukaemia: 6p24–25 and 12p12–13 translocations, 4q21 anomalies and monosomy 21

Molecular abnormalities in B-cell chronic lymphocytic leukaemia

Contact Info

Product

Resources

About