Cases with partial trisomy 12 have rarely been found in B-cell chronic lymphocytic leukemia (CLL). We report our clinical, cytogenetic and fluorescence in situ hybridization (FISH) findings in a CLL patient with a duplication of part of the long arm of chromosome 12 between bands q13–q22. This patient was the only case with this duplication among the 112 cases (0.9%) of CLL cytogenetically analyzed in our laboratory. FISH studies using unique-sequence specific probes for the RB-1 (retinoblastoma) gene and the D13S319 locus at the 13q14 band showed a monoallelic loss for the D13S319 locus (20% of cells) with a diploid RB-1 gene. Our case showed an atypical morphology (35% prolymphocytes), a high proliferation rate and progression of the disease, indicating that the duplication of this region may be equivalent to complete trisomy 12 in CLL patients.

Keywords:
Chronic lymphocytic leukemia, Partial trisomy 12, 13q14 deletion, Atypical lymphocytes, Cytogenetics
1.
Juliusson G, Oscier DG, Fitchett M, Ross FM, Stockdill G, Mackie MJ, Parker AC, Castoldi GL, Cuneo A, Knuutila S, Elonen E, Gahrton G: Prognostic subgroups in B-cell chronic lymphocyte leukemia defined by specific chromosomal abnormalities. N Engl J Med 1990;323:720–724.
2.
Oscier DG: Cytogenetic and molecular abnormalities in chronic lymphocytic leukemia. Blood Rev 1994;8:88–97.
3.
Perez-Losada A, Wessman M, Tiainen M, Hopman AH, Willard HF, Sole F, Caballin MR, Woessner S, Knuutila S: Trisomy 12 in chronic lymphocytic leukemia: An interphase cytogenetic study. Blood 1991;78:775–779.
4.
Anastasi J, Le Beau MM, Vardiman JW, Fernald AA, Larson RA, Rowley JD: Detection of trisomy 12 in chronic lymphocytic leukemia by fluorescence in situ hybridization to interphase cells: A single and sensitive method. Blood 1992;79:1796–1801.
5.
Dohner H, Pohl S, Bulgay-Morschel M, Stilgenbauer S, Bentz M, Lichter P: Trisomy 12 in chronic lymphocytic leukemias – A metaphase and interphase cytogenetic analysis. Leukemia 1993;7:516–520.
6.
Que TH, Marco JG, Ellis J, Matutes E, Babapulle VB, Boyle S, Catovsky D: Trisomy 12 in chronic lymphocytic leukemia detected by fluorescence in situ hybridization: Analysis by stage, immunophenotype, and morphology. Blood 1993;82:571–575.
7.
Gahrton G, Robert K-H, Friberg K, Juliusson G, Biberfeld P, Zech L: Cytogenetic mapping of the duplicated segment of chromosome 12 in lymphoproliferative disorders. Nature 1982;297:513–514.
8.
Mecucci C, Delannoy A, Van Den Berghe H: The origin of trisomy 12 in B-cell chronic lymphocytic leukemia. Cancer Genet Cytogenet 1988;36:203–204.
9.
McManus AP, Bailie KEM, Jess H, Desai ZR: A derivative chromosome 14 resulting in partial trisomy of chromosome 12 in B-cell chronic lymphocytic leukemia. Cancer Genet Cytogenet 1994;76:159–160.
10.
Merup M, Juliusson G, Wu X, Jansson M, Stellan B, Rasool O, Stenman G, Gahrton G, Einhorn S: Amplification of multiple regions of chromosome 12, including 12q13–15, in chronic lymphocytic leukemia. Eur J Haematol 1997;58:174–180.
11.
Zech L, Mellstedt H: Chromosome 13 – A new marker for B-cell chronic leukemia. Hereditas 1988;108:77–84.
12.
Stilgenbauer S, Döhner H, Bulgay-Mörschel M, Weitz S, Bentz M, Lichter P: High frequency of monoallelic retinoblastoma gene deletion in B-cell chronic lymphoid leukemia shown by interphase cytogenetic. Blood 1993;81:2118–2124.
13.
Döhner H, Pilz T, Fischer K, Cabot G, Diehl D, Fink T, Stilgenbauer S, Bentz M, Lichter P: Molecular cytogenetics analysis of RB-1 deletions in chronic B-cell leukemias. Leuk Lymphoma 1994;16:97–103.
14.
Liu Y, Hermanson M, Grander D, Merup M, Wu X, Heyman M, Rasool O, Juliusson G, Gahrton G, Detlofsson R, Nikiforova N, Buys C, Söderhall S, Yankovsky N, Zabarovsky E, Einhorn S: 13q deletions in lymphoid malignancies. Blood 1995;86:1911–1915.
15.
Stilgenbauer S, Leupolt E, Ohl S, Weiss G, Schröder M, Fischer K, Bentz M, Lichter P, Döhner H: Heterogenity of deletions involving RB-1 and the D13S25 locus in B-cell chronic lymphocytic leukemia revealed by fluorescence in situ hybridization. Cancer Res 1995;55:3475–3477.
16.
Garcia-Marco JA, Price CM, Catovsky D: Interphase cytogenetics in chronic lymphocytic leukemia. Cancer Genet Cytogent 1997;94:52–58.
17.
Matutes E, Owusu-Ankomah K, Morilla R, Garcia Marco J, Houlihan A, Que TH, Catovsky D: The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia 1994;8:1640–1645.
18.
Seabright, M: Rapid banding technique for human chromosomes. Lancet 1971;ii:971–972.
19.
Mitelman F (ed): ISCN. Guidelines for cancer cytogenetics, supplement to an International System for Human Cytogenetic Nomenclature. Basel, Karger, 1991.
20.
Peterson LC, Lindquist LL, Church S, Kay NE: Frequent clonal abnormalities of chromosome band 13q14 in B-cell chronic lymphocytic leukemia: Multiple clones, subclones, and nonclonal alterations in 82 midwestern patients. Genes Chrom. Cancer 1992;4:273–280.
21.
Mould S, Gardiner M, Corcoran M, Oscier DG: Trisomy 12 and structural abnormalities of 13q14 occurring in the same clone in chronic lymphocytic leukemia. B J Haematol 1996;92:389–392.
22.
Navarro B, Garcia-Marco JA, Jones D, Price CM, Catovsky D: Association and clonal distribution of trisomy 12 and 13q14 deletions in chronic lymphocytic leukaemia. Br J Haematol 1998;102:1330–1334.
23.
Chena CH, Pedrazzini E, Sarmiento M, Arrossagaray G, Bengio R, Slavutsky I: Molecular genetics in chronic lymphocytic leukemia. Cytogenet Cell Genet 1999;85:66.
24.
Hogan WJ, Tefferi A, Borell TJ, Jenkins R, Li CY, Witzig TE: Prognosis relevance of monosomy at the 13q14 locus detected by fluorescence in situ hybridization in B-cell chronic lymphocytic leukemia. Cancer Genet Cytogenet 1999;110:77–81.
25.
Dierlamm J, Wlodarska I, Michaux L, Vermeesch JR, Meeus P, Stul M, Criel A, Verhoef G, Thomas J, Delannoy A, Louwagie A, Cassiman J-J, Mecucci C, Hagemeijer A, Van Den Berghe H: FISH identified different types of duplications with 12q13–15 as commonly involved segment in B-cell lymphoproliferative malignancies characterized by partial trisomy 12. Genes Chrom Cancer 1997;20:155–166.
26.
Stock AD, Dennis TR: A translocation breakpoint at chromosome band 12q13 associated with B-cell chronic lymphocytic leukemia. Cancer Genet Cytogenet 1999;111:166–168.
27.
Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 1992;358:80–83.
28.
Finlay CA: The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth. Mol Cell Biol 1993;13:301–306.
29.
Watanabe T, Hotta T, Ichikawa A, Kinoshita T, Nagai H, Uchida T, Murate T, Saito H: The MDM2 oncogene overexpression in chronic lymphocytic leukemia and low-grade lymphoma of B-cell origin. Blood 1994;84:3158–3165.
30.
Huang YQ, Raphael B, Buchbinder A, Li, JJ, Zhang WG, Friedman-Kien AE: Rearrangement and expression of MDM2 oncogene in chronic lymphocytic leukemia. Am J Hematol 1994;47:139–141.
© 2001 S. Karger AG, Basel
2001
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.