In B-cell chronic lymphocytic leukaemia chromosome 17 abnormalities and not trisomy 12 are the single most important cytogenetic abnormalities for the prognosis: A cytogenetic and immunophenotypic study of 480 unselected newly diagnosed patients

Geisler, Christian H.; Philip, Preben; Christensen, B.; Hou‐Jensen, Klaus; Pedersen, Niels Tinggaard; Jensen, O. Myhre; Thorling, K; Andersen, Erik André; Birgens, Henrik; Drivsholm, Aage; Ellegaard, Jørgen; Jk, Larsen; Plesner, Trine Lindhardt; Brown, Peter N.; Andersen, Per Kragh; Hansen, Mogens

doi:10.1016/s0145-2126(97)00095-7

Cited by 102 publications

(64 citation statements)

References 20 publications

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“…A subset of genomic aberrations was identified as important independent predictors of disease progression and survival 3 . Deletions of 11q and 17p, affecting the ataxia telangiectasia mutated (ATM) gene and p53 tumor suppressor gene (TP53) respectively, have been associated with disease progression and reduced survival [4][5][6][7] . Early identification of these deletions could allow clinicians to choose appropriate therapy for these patients 8,9 .…”

Section: Introductionmentioning

confidence: 99%

Array-based karyotyping in chronic lymphocytic leukemia (CLL) detects new unbalanced abnormalities that escape conventional cytogenetics and CLL FISH panel

Urbánková¹,

Papajík²,

Plachy³

et al. 2014

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Aims. Chronic lymphocytic leukemia (CLL) is the most common adult leukemia with a very heterogeneous course. Progress in molecular genetic characterization of CLL has confirmed the prognostic role of unbalanced chromosomal abnormalities currently defined by molecular cytogenetic methods: conventional karyotyping and FISH. However, a significant percentage of genomic abnormalities escapes routine investigation due to the limitations of these methods. It is presently clear that some of these aberrations have impact on prognosis and disease progression. Methods. We examined copy number changes in the tumor genomes of 50 CLL patients using bacterial artificial chromosome (BAC) and/or oligonucleotide array platforms. We compared the results of arrayCGH with those obtained by FISH and conventional cytogenetics and evaluated their clinical importance. Results. A total of 111 copy number changes were detected in 43 patients (86%) with clonal abnormalities present in at least 23% of the cells. Moreover, 14 patients (28%) were found to have 39 genomic changes that had not been detected by standard cytogenetic and/or FISH analyses. These included possibly prognostically important recurrent 2p and 8q24 gains. The most frequent unbalanced changes involved chromosomes 18, 7, 3, 9 and 17. We also determined the minimal deleted region on chromosome 6q in 7 cases by chromosome 6/7 specific array. Conclusions. The results showed that a subset of potentially significant genomic aberrations in CLL is being missed by the current routine techniques. Further, we clearly demonstrated the robustness, high sensitivity and specificity of the arrayCGH analysis as well as its potential for use in routine screening of CLL.

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Section: Introductionmentioning

confidence: 99%

Array-based karyotyping in chronic lymphocytic leukemia (CLL) detects new unbalanced abnormalities that escape conventional cytogenetics and CLL FISH panel

Urbánková¹,

Papajík²,

Plachy³

et al. 2014

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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“…Until recently, the study of CLL cytogenetics had been hampered by the low mitotic activity of CLL cells in vitro, with abnormal metaphases being recovered in less than one-third of patients. 1 The advent of interphase fluorescent in situ hybridization (FISH) studies has shown that more than 80% of CLLs harbor recurrent genetic aberrations, and that the most common aberrations can be arranged in a hierarchical classification strongly predictive of survival. 2 In this classification, patients with the chromosome 17p13.1 deletion (17pϪ, as identified by loss of TP53) had the worst prognosis, with a median survival of 2 to 3 years from initial diagnosis.…”

Section: Introductionmentioning

confidence: 99%

De novo deletion 17p13.1 chronic lymphocytic leukemia shows significant clinical heterogeneity: the M. D. Anderson and Mayo Clinic experience

Tam

Shanafelt

Wierda

et al. 2009

Blood

147

114

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To determine the clinical fate of patients with de novo deletion 17p13.1 (17p؊) chronic lymphocytic leukemia (CLL), we retrospectively studied the outcome of 99 treatment-naive 17p؊ CLL patients from the M. D. Anderson Cancer Center (n ‫؍‬ 64) and the Mayo Clinic (n ‫؍‬ 35). Among 67 asymptomatic patients followed for progression, 53% developed CLL requiring treatment over 3 years. Patients who had not progressed by 18 months subsequently had stable disease, with 3 of 19 patients progressing after follow-up of up to 70 months. Risk factors for progressive disease were Rai stage of 1 or higher and unmutated immunoglobulin variable region heavy chain (IgVH). The overall survival rate was 65% at 3 years. Rai stage 1 or higher, unmutated IgVH, and 17p؊ in 25% or more of nuclei were adverse factors for survival. The 3-year survival rates of patients with 1 or fewer, 2, and 3 of these factors were 95%, 74%, and 22%, respectively (P < .001). Response rates to therapy with rituximab (n ‫؍‬ 6); purine analogues and rituximab (n ‫؍‬ 25); and purine analogues, rituximab, and alemtuzumab (n ‫؍‬ 16) combinations were 50%, 72%, and 81%, respectively. Patients with 17p؊ CLL exhibit clinical heterogeneity, with some patients experiencing an indolent course. Survival can be predicted using clinical and biologic characteristics.

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“…1,[3][4][5][6] Chromosomal translocation t(2;14) (p13;q32.3) is one example and has been reported in a variety of B-cell malignancies ranging from B-cell precursor acute lymphoblastic leukemia to myeloma. This translocation is frequently the sole cytogenetic abnormality within the neoplastic clone (Watson et al, 7 Geisler et al, 8 Sonoki et al, 9 and http://cgap.nci.nih.gov/ Chromosomes/Mitelman). We report here the recurrent involvement and deregulated expression of a Krüppel zinc finger gene, BCL11A, in 4 cases of B-cell malignancy with t(2;14)(p13;q32.3).…”

Section: Introductionmentioning

confidence: 99%

The BCL11 gene family: involvement of BCL11A in lymphoid malignancies

Satterwhite

Sawada

Willis

et al. 2001

Blood

274

286

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region, is the pathologic target. However, by molecular cloning of t(2;14)(p13;q32.3) from 3 cases of aggressive B-cell chronic lymphocytic leukemia (CLL)/immunocytoma, this study has shown clustered breakpoints on chromosome 2p13 immediately upstream of a CpG island located about 300 kb telomeric of REL. This CpG island was associated with a Krü ppel zinc finger gene (BCL11A), which is normally expressed at high levels only in fetal brain and in germinal center B-cells. There were 3 major RNA isoforms of BCL11A, differing in the number of carboxy-terminal zinc fingers. All 3 RNA isoforms were deregulated as a consequence of t(2;14) (p13;q32.3). BCL11A was highly conserved, being 95% identical to mouse, chicken, and Xenopus homologues. BCL11A was also highly homologous to another gene ( IntroductionMany subtypes of malignancy are associated with specific chromosomal translocations, which play a pivotal role in the pathogenesis of disease. In the leukemias and lymphomas of mature B-cells, these frequently involve the immunoglobulin (IG) loci and result in deregulated expression of the translocated oncogene, due, in part, to the presence of potent B cell-specific transcriptional enhancers within the IG loci. 1 All the common IG translocations have been cloned. Paradigms include the deregulation of cyclin D1 by t(11;14)(q13;q32.3), found in all cases of mantle cell lymphoma; BCL2 by t(14;18)(q32.3;q21.3), found in 80% of follicular lymphoma; and MYC by t(8;14)(q24.1;q32.3) and variant translocations in all cases of Burkitt lymphoma. 1 On the basis of cytogenetics alone, several rare, but nonetheless recurrent IG translocations remain to be cloned, principally in aggressive large-cell B-NHL 2 ; their molecular cloning continues to allow the isolation of novel dominant oncogenes and to define new pathogenic mechanisms. 1,[3][4][5][6] Chromosomal translocation t(2;14) (p13;q32.3) is one example and has been reported in a variety of B-cell malignancies ranging from B-cell precursor acute lymphoblastic leukemia to myeloma. This translocation is frequently the sole cytogenetic abnormality within the neoplastic clone (Watson et al,7 Geisler et al, 8 Sonoki et al, 9 and http://cgap.nci.nih.gov/ Chromosomes/Mitelman). We report here the recurrent involvement and deregulated expression of a Krüppel zinc finger gene, BCL11A, in 4 cases of B-cell malignancy with t(2;14)(p13;q32.3). Patients, materials, and methods Patient materialFour patients with B-cell malignancies and t(2;14)(p13;q32) were studied. Patient material was studied after obtaining written informed consent and local ethical committee approval. Two unusual pediatric patients with CLL (referred to here as patients AS and LH) who exhibited this translocation have been reported on previously 10 ; the translocation breakpoints in these 2 cases were cloned using bacteriophage cloning. 11 In addition, 2 adult patients identified from our cytogenetic databases with identical translocations were also studied. Patient 3 was a previously well 62-year-old female who pres...

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In B-cell chronic lymphocytic leukaemia chromosome 17 abnormalities and not trisomy 12 are the single most important cytogenetic abnormalities for the prognosis: A cytogenetic and immunophenotypic study of 480 unselected newly diagnosed patients

Cited by 102 publications

References 20 publications

Array-based karyotyping in chronic lymphocytic leukemia (CLL) detects new unbalanced abnormalities that escape conventional cytogenetics and CLL FISH panel

Array-based karyotyping in chronic lymphocytic leukemia (CLL) detects new unbalanced abnormalities that escape conventional cytogenetics and CLL FISH panel

De novo deletion 17p13.1 chronic lymphocytic leukemia shows significant clinical heterogeneity: the M. D. Anderson and Mayo Clinic experience

The BCL11 gene family: involvement of BCL11A in lymphoid malignancies

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