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Common chromatin structures at breakpoint cluster regions may lead to chromosomal translocations found in chronic and acute leukemias

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Abstract

The t(9;22) BCR/ABL fusion is associated with over 90% of chronic myelogenous and 25% of acute lymphocytic leukemia. Chromosome 11q23 translocations in acute myeloid and lymphoid leukemia cells demonstrate myeloid lymphoid leukemia (MLL) fusions with over 40 gene partners, like AF9 and AF4 on chromosomes 9 and 4, respectively. Therapy-related leukemia is associated with the above gene rearrangements following the treatment with topoisomerase II (topo II) inhibitors. BCR, ABL, MLL, AF9 and AF4 have defined patient breakpoint cluster regions. Chromatin structural elements including topo II and DNase I cleavage sites and scaffold attachment sites have previously been shown to closely associate with the MLL and AF9 breakpoint cluster regions, implicating these elements in non-homologous recombination (NHR). In this report, using cell lines and primary cells, chromatin structural elements were analyzed in BCR, ABL and AF4 and, for comparison, in MLL2, which is a homolog to MLL, but not associated with chromosome translocations. Topo II and DNase I cleavage sites associated with all breakpoint cluster regions, whereas SARs associated with ABL and AF4, but not with BCR. No close breakpoint clustering with the topo II/DNase I sites were observed; however, a statistically significant 5′ or 3′ distribution of patient breakpoints to the topo II DNase I sites was found, implicating DNA repair and exonucleases. Although MLL2 was expressed in all cell lines tested, except for the presence of one DNAse I site in the promoter, no other structural elements were found in MLL2. A NHR model presented demonstrates the importance of chromatin structure in chromosome translocations involved with leukemia.

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References

  • Abeysinghe SS, Chuzhanova N, Krawczak M, Ball EV, Cooper DN (2003) Translocation and gross deletion breakpoints in human inherited disease and cancer I: Nucleotide composition and recombination-associated motifs. Hum Mut 22:229–244

    Article  PubMed  CAS  Google Scholar 

  • Advani AS, Pendergast AM (2002). Bcr-Abl variants: biological and clinical aspects. Leuk Res 26:713–720

    Article  PubMed  CAS  Google Scholar 

  • Aplan PD, Chervinsky DS, Stanulla M, Burhans WC (1996) Site-specific DNA cleavage within the MLL breakpoint cluster region induced by topoisomerase II inhibitors. Blood 87:2649–2658

    PubMed  CAS  Google Scholar 

  • Asami Y, Jia DW, Tatebayashi K, Yamagata K, Tanokura M, Ikeda H (2002) Effect of the DNA topoisomerase II inhibitor VP-16 on illegitimate recombination in yeast chromosomes. Gene 291:251–257

    Article  PubMed  CAS  Google Scholar 

  • Bae YS Kawasaki I, Ikeda H, Liu LF (1988) Illegitimate recombination mediated by calf thymus DNA topoisomerase II in vitro. Proc Natl Acad Sci USA 85:2076–2080

    Article  Google Scholar 

  • Baxter EJ, Hochhaus A, Bolufer P, Reiter A, Fernandez JM, Senent L, Cervera J, Moscardo F, Sanz MA, Cross NC (2002) The t(4;22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA. Hum Mol Genet 11:1391–1397

    Article  PubMed  CAS  Google Scholar 

  • Betti CJ, Villalobos MJ, Diaz MO, Vaughan AT (2001) Apoptotic triggers initiate translocations within the MLL gene involving the nonhomologous end joining repair system. Cancer Res 61:4550–4555

    PubMed  CAS  Google Scholar 

  • Blanco JG, Edick MM, Relling MV (2004) Etoposide induces chimeric Mll gene fusions. FASEB J 18: 173–175

    PubMed  CAS  Google Scholar 

  • Bloomfield CD, Archer KJ, Mrozek K, Linnington DM, Kanko Y, Head DR, Dai Cin P, Ramondi SC (2002) 11q23 balanced chromosome aberrations in treatment-related myelodysplastic syndromes and acute leukemia: Report from an international workshop. Geneshromosomes Cancer 33:362–378

    Google Scholar 

  • Bode J, Benham C, Ernst E, Knopp A, Marschalek R, Strick R, Strissel P (2000) Fatal connections: when DNA ends meet on the nuclear matrix. J Cell Biochem 35:3–22

    Article  Google Scholar 

  • Borgnetto ME, Zunino F, Tinelli S, Kas E, Capranico G (1996) Drug-specific sites of topoisomerase II DNA cleavage in Drosophila chromatin: heterogeneous localization and reversibility. Cancer Res 56:1855–1862

    PubMed  CAS  Google Scholar 

  • Charron M, Hancock R (1991) Chromosome recombination and defective genome segregation induced in Chinese hamster cells by the topoisomerase II inhibitor VM-26. Chromosoma 100:97–102

    Article  PubMed  CAS  Google Scholar 

  • Chissoe SL, Bodenteich A, Wang YF, Wang YP, Burian D, Clifton SW, Crabtree J, Freeman A, Iyer K, Jian L, Yichen M, et al (1995) Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal translocation. Genomics 27:67–82

    Article  PubMed  CAS  Google Scholar 

  • Clemens MJ, Bushell M, Morley SJ (1998) Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines. Oncogene 17:2921–2931

    Article  PubMed  CAS  Google Scholar 

  • Demiroglu A, Steer EJ, Heath C, Taylor K, Bentley M, Allen SL, Koduru P, Brody JP, Hawson G, Rodwell R and Doody ML, et al (2001) The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins. Blood 98:3778–3783

    Article  PubMed  CAS  Google Scholar 

  • Domer PH, Head DR, Renganathan N, Raimondi SC, Yang E, Atlas M (1995) Molecular analysis of 13 cases of MLL/11q23 secondary acute leukemia and identification of topoisomerase II consensus-binding sequences near the chromosomal breakpoint of a secondary leukemia with the t(4;11). Leukemia 9:1305–1312

    PubMed  CAS  Google Scholar 

  • Durrieu F, Samejima K, Fortune JM, Kandels-Lewis S, Osheroff N, Earnshaw WC (2000) DNA topoisomerase II alpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution. Curr Biol 10:923–926

    Article  PubMed  CAS  Google Scholar 

  • Echlin-Bell DR, Smith LL, Li L, Strissel PL, Strick R, Gupta V, Banerjee J, Larson R, Relling MV, Raimondi SC, Hayashi Y, Taki T, Zeleznik-Le N, Rowley JD (2003) Polymorphisms in the MLL BCR. Hum Genet 113:80–91

    PubMed  CAS  Google Scholar 

  • Elliott B, Jasin M (2002) Double-strand breaks and translocations in cancer. Cell Mol Life Sci 59:373–385

    Article  PubMed  CAS  Google Scholar 

  • Filipski J, Leblanc J, Youdale T, Sikorska M, Walker PR (1990) Periodicity of DNA folding in higher order chromatin structures. EMBO J 9:1319–1327

    PubMed  CAS  Google Scholar 

  • Fitzgerald KT, Diaz MO (1999) MLL2, A new mammalian member of the trx/MLL family of genes. Genomics 59:187–192

    Article  PubMed  CAS  Google Scholar 

  • Greaves MF (1996) Infant leukaemia biology, aetiology and treatment. Leukemia 10:372–377

    PubMed  CAS  Google Scholar 

  • Gu Y, Nakamura T, Alder H, Prasad R, Canaani O, Cimino G, Canaani E (1992) The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax to the AF-4 gene. Proc Natl Acad Sci USA 71:701–708

    CAS  Google Scholar 

  • Hensel JP, Gellert E, Fey GH, Marschalek R (2001) Breakpoints of t(4;11) translocations in the human MLL and AF4 genes in ALL patients are preferentially clustered outside of high-affinity matrix attachment regions. J Cell Biochem 82:299–309

    Article  PubMed  CAS  Google Scholar 

  • Huang Y, Nakada S, Ishiko T, Utsugisawa T, Datta R, Kharbanda S, Yoshida K, Talanian RV, Weichselbaum R, Kufe D, Yuan ZM (1999) Role for caspase-mediated cleavage of Rad51 in induction of apoptosis by DNA damage. Mol Cell Biol 4:2986–2997

    Google Scholar 

  • Huntsman DG, Chin SF, Muleris M, Batley SJ, Collins VP, Wiedemann L M, Aparicio S, Caldas C (1999) MLL2 the second human homolog of the Drosophila trithorax gene, maps to 19q13.1 and is amplified in solid tumor cell lines. Oncogene 18:7975–7984

    Article  PubMed  CAS  Google Scholar 

  • Iarovala OV, Shkumatov P, Razin SV (2004) Breakpoint cluster regions of the AML-1 and ETO genes contain MAR elements and are preferentially associated with the nuclear matrix in proliferating HEL cells. J Cell Sci 117:4583–4590

    Article  Google Scholar 

  • Jeffs AR, Benjes SM, Smith TL, Sowerby SJ, Morris CM (1998) The BCR gene recombines preferentially with Alu elements in complex BCR-ABL translocations of chronic myeloid leukaemia. Hum Mol Gen 7:767–776

    Article  PubMed  CAS  Google Scholar 

  • Jeffs AR, Wells E, Morris CM (2001) Nonrandom distribution of interspersed repeat elements in the BCR and ABL1 genes and its relations to breakpoint cluster regions. Genes Chromosomes Cancer 92:144–154

    Article  Google Scholar 

  • Jiang X Trujillo JM, Liang JC (1990) Chromosomal breakpoints within the first intron of the ABL gene are nonrandom in patients with chronic myelogenous leukemia. Blood 76:597–601

    Google Scholar 

  • Khobta A, Carlo-Stella C, Capranico G (2004) Specific histone patterns and acetylase/deacetylase activity at the breakpoint-cluster region of the human MLL gene. Cancer Res 64:2656–2662

    Article  PubMed  CAS  Google Scholar 

  • Kingma PS, Greider CA, Osheroff N (1997) Spontaneous DNA lesions poison human topoisomerase II alpha and stimulate cleavage proximal to leukemic 11q23 chromosomal breakpoints. Biochemistry 36:5934–5939

    Article  PubMed  CAS  Google Scholar 

  • Langer T, Metzler M, Reinhardt D, Viehmann S, Borkhardt A, Reichel M, Stanulla M, Schrappe M, Creutzig U, Ritter J, Leis, et al (2003) Analysis of t(9;11) chromosomal breakpoint sequences in childhood acute leukemia: almost identical MLL breakpoints in therapy-related AML after treatment without etoposides. Genes Chromosomes Cancer 36:393–401

    Article  PubMed  CAS  Google Scholar 

  • Langst G, Schatz T, Langowski J, Grummt I (1997) Structural analysis of mouse rDNA: coincidence between nuclease hypersensitive sites, DNA curvature and regulatory elements in the intergenic spacer. Nucleic Acids Res 25:511–517

    Article  PubMed  CAS  Google Scholar 

  • Liu LF (1989) DNA topoisomerase poisons as antitumor drugs. Annu Rev Biochem 58:351–375

    Article  PubMed  CAS  Google Scholar 

  • Lovett BD, Nigro L, Rappaport EF, Blair IA, Osheroff N, Zheng N, Megonigal MD, Williams WR, Nowell PC, Felix CA (2001) Near-precise interchromosomal recombination and functional DNA topoisomerase II cleavage sites at MLL and AF-4 genomic breakpoints in treatment-related acute lymphoblastic leukemia with t(4;11) translocation. Proc Natl Acad Sci USA 98:9802–9807

    Article  PubMed  CAS  Google Scholar 

  • Mitelman F (1994) Catalog of chromosome aberrations in cancer 5th edn. Wiley–Liss, New York

    Google Scholar 

  • Mondal N, Parvin JD (2001) DNA topoisomerase II alpha is required for RNA polymerase II transcription on chromatin templates. Nature 413:435–438

    Article  PubMed  CAS  Google Scholar 

  • Nakamura T, Alder H, Gu Y, Prasad R, Canaani O, Kamada N, Gale RP, Lange B, Crist WM, Nowell PC, Croce CM, Canaani E (1993) Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs. Proc Natl Acad Sci USA 90:4631–4635

    Article  PubMed  CAS  Google Scholar 

  • Negrini M, Felix CA, Martin C, Lange BJ, Nakamura T, Canaani E, Croce CM (1993) Potential topoisomerase II DNA-binding sites at the breakpoints of a t(9;11) chromosome translocation in acute myeloid leukemia. Cancer Res 53:4489–4492

    PubMed  CAS  Google Scholar 

  • Papadopoulos P, Ridge SA, Boucher CA, Stocking C, Wiedemann LM (1995) The novel activation of ABL by fusion to an ets-related gene, TEL. Cancer Res 55:34–38

    PubMed  CAS  Google Scholar 

  • Pedersen-Bjergaard J, Brondum-Nielsen K, Karle H, Johansson B (1997) Chemotherapy-related-late occurring-Philadelphia chromosome in AML, ALL and CML. Similar events related to treatment with DNA topoisomerase II inhibitors? Leukemia 11:1571–1574

    Article  PubMed  CAS  Google Scholar 

  • Pierce AJ, Hu P, Han M, Ellis N, Jasin M (2001) Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells. Genes Dev 15: 3237–3242

    Article  PubMed  CAS  Google Scholar 

  • Rassool FV (2003) DNA double strand breaks (DSB) and non-homologous end joining (NHEJ) pathways in human leukemia. Cancer Lett 193:1–9

    Article  PubMed  CAS  Google Scholar 

  • Reichel M, Gillert E, Angermuller S, Hensel JP, Heidel F, Lode M, Leis T, Biondi A, Haas OA, Strehl S, Panzer-Grumayer, et al (2001) Biased distribution of chromosomal breakpoints involving the MLL gene in infants versus children and adults with t(4;11) ALL. Oncogene 20:2900–2907

    Article  PubMed  CAS  Google Scholar 

  • Reichel M, Gillert E, Nilson I, Siegler G, Gre il J, Fey GH, Marschalek R (1998) Fine structure of translocation breakpoints in leukemic blasts with chromosomal translocation t(4;11): the DNA damage-repair model of translocation. Oncogene 17:3035–3044

    Article  PubMed  CAS  Google Scholar 

  • Reichel M, Gillert E, Breitenlohner I, Repp R, Greil J, Beck JD, Fey GH, Marschalek R (1999) Rapid isolation of chromosomal breakpoints from patients with t(4;11) acute lymphoblastic leukemia. Cancer Res 59:3357–3362

    PubMed  CAS  Google Scholar 

  • Reilling MV, Yanishevski Y, Nemec I, Evans WE, Boyett JM, Behm FG, Pui C-H (1998) Etoposide and antimetabolite pharmacology in patients who develop secondary acute myeloid leukemia. Leukemia 12:346–352

    Article  Google Scholar 

  • Ross JA (2000) Dietary flavonoids and the MLL gene: a pathway to infant leukemia? Proc Natl Acad Sci USA 97:4411–4413

    Article  PubMed  CAS  Google Scholar 

  • Rowley JD (1999) The role of chromosome translocations in leukemogenesis. Semin Hematol 36:59–72

    PubMed  CAS  Google Scholar 

  • Rowley J, Olney HJ (2002) International workshop on the relationship of prior therapy to balanced chromosome aberrations in therapy-related myelodysplastic syndromes and acute leukemia: Overview report. Genes Chromosomes Cancer 33:331–345

    Article  PubMed  Google Scholar 

  • Saglio G, Storlazzi CT, Giugliano E, Surace C Anelli L, Rege-Cambrin G, Zagaria A, Jimenez Velasco A, Heiniger A, Scaravaglio P, Torres Gomez A, et al (2002) 76-kb duplicon maps close to the BCR gene on chromosome 22 and the ABL gene on chromosome 9: possible involvement in the genesis of the Philadelphia chromosome translocation. Proc Natl Acad Sci USA 99:9882–9887

    Article  PubMed  CAS  Google Scholar 

  • Salovoyan VT, Bezvenyuk ZA, Salminen A, Austin CA, Courtney MJ (2002) The role of topoisomeras II in the excision of DNA loop domains during apoptosis. J Biol Chem 277:21458–21467

    Article  Google Scholar 

  • Schaefer-Rego KE, Leibowitz D, Mears JG (1990) Chromatin alterations surrounding the BCR/ABL fusion gene in K562 cells. Oncogene 5:1669–1673

    PubMed  CAS  Google Scholar 

  • Schichman S, Caligiuri M, Gu Y, Strout M, Canaani E, Bloomfield CD, Croce CM (1994) ALL-1 partial duplication in acute leukemia. Proc Natl Acad Sci USA 91:6236–6239

    Article  PubMed  CAS  Google Scholar 

  • Sinclair PB, Nacheva EP, Leversha M, Telford N, Chang J, Reid A, Bench A, Champion K, Huntly B, Green AR (2000) Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia. Blood 95:738–743

    PubMed  CAS  Google Scholar 

  • Spence JM, Critcher R, Ebersole TA, Valdivia M M, Earnshaw W C, Fukagawa T, Farr CJ (2002) Co-localization of centromere activity, proteins and topoisomerase II within a subdomain of the major human X alpha satellite array. EMBO J 21:5269–5280

    Article  PubMed  CAS  Google Scholar 

  • Sperry AO, Blasquez VC, Garrard WT (1989) Dysfunction of chromosomal loop attachment sites: Illegitimate recombination linked to matrix association regions and topoisomerase II. Proc Natl Acad Sci USA 86:5497–5501

    Article  PubMed  CAS  Google Scholar 

  • Spitzner JR, Muller MT (1988) A consensus sequence for cleavage by vertebrate DNA topoisomerase II. Nucleic Acids Res 16:5533–5556

    Article  PubMed  CAS  Google Scholar 

  • Stanulla M, Wang J, Chervinsky DS, Thandla S, Aplan PD (1997) DNA cleavage within the MLL breakpoint cluster region is a specific event which occurs as part of higher-order chromatin fragmentation during the initial stages of apoptosis. Mol Cell Biol 17:4070–4079

    PubMed  CAS  Google Scholar 

  • Strick R, Laemmli UK (1995) SARs are cis elements of chromosome dynamics: synthesis of a SAR repressor protein. Cell 83:1137–1148

    Article  PubMed  CAS  Google Scholar 

  • Strick R, Strissel PL, Borgers S, Smith SL, Rowley J D (2000) Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia. Proc Natl Acad Sci USA 97:4790–4795

    Article  PubMed  CAS  Google Scholar 

  • Strick R, Strissel PL, Gavrilov K, Levi-Setti R (2001) Cation-chromatin binding as shown by ion microscopy is essential for the structural integrity of chromosomes. J Cell Biol 155:899–910

    Article  PubMed  CAS  Google Scholar 

  • Strissel PL, Espinosa RIII, Rowley JD, Swift H (1996a) Scaffold attachment regions in centromere-associated DNA. Chromosoma 105:122–133

    Article  CAS  Google Scholar 

  • Strissel PL, Gill-Super H, Thirman MJ, Pomykala H, Yonebayashi Y, Tanabe S, Zeleznik-Le N, Rowley JD (1996b) Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment related acute myeloid leukemia: Correlation with scaffold attachment regions and topoisomerase II consensus binding sites. Blood 87:1912–1922

    Google Scholar 

  • Strissel PL, Hadan HA, Pomykala HM, Diaz MO, Rowley JD, Olopade OI (1998a) Scaffold associated regions in the human type I interferon gene cluster on the short arm of chromosome 9. Genomics 47:217–229

    Article  CAS  Google Scholar 

  • Strissel PL, Strick R, Rowley JD, Zeleznik-Le NJ (1998b) An in vivo topoisomerase II cleavage site and a DNase I hypersensitive site colocalize near exon 9 in the MLL breakpoint cluster region. Blood 92:3793–3803

    CAS  Google Scholar 

  • Strissel PL, Strick R, Tomek R J, Roe B, Zeleznik-Le N (2000) AF9, a common partner gene in MLL translocations of leukemia patients, demonstrates similar DNA structural properties to MLL that could act as recombination “hot spots”. Hum Mol Genet 9:1671–1679

    Article  PubMed  CAS  Google Scholar 

  • Taki T, Kano H, Taniwaki M, Sako M, Yanagisawa M, Hayashi Y (1999) AF5q31, a newly identified AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia with ins(5;11)(q31;q13q23). Proc Natl Acad Sci USA 96:14535–14540

    Article  PubMed  CAS  Google Scholar 

  • Tennyson RB, Ebran N, Herrera AE, Lindsley JE (2002) A novel selection system for chromosome translocations in Saccharomyces cerevisiae. Genetics 160:1363–1373

    PubMed  CAS  Google Scholar 

  • Timmons MS, Witte ON (1989) Structural characterization of the BCR gene product. Oncogene 4:559–567

    PubMed  CAS  Google Scholar 

  • Udvardy A, Schedl P (1991) Chromatin structure, not DNA sequence specificity, is the primary determinant of topoisomerase II sites of action in vivo. Mol Cell Biol 11:4973–4984

    PubMed  CAS  Google Scholar 

  • van der Burg M, Beverloo HB, Langerak AW, Wijsman J, van Drunen E, Slater R, van Dongen JJ (1999) Rapid and sensitive detection of all types of MLL gene translocations with a single FISH probe set. Leukemia 13:2107–2113

    Article  PubMed  Google Scholar 

  • von Bergh AR, Beverloo HB, Rombout P, van Wering ER, van Weel MH, Beverstock GC, Kluin PM, Slater RM, Schuuring E (2002) LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia. Genes Chromosomes Cancer 35:92–96

    Article  Google Scholar 

  • Watt PM, Hickson ID (1994) Structure and function of type II DNA topoisomerases. J Biochem 303:681–695

    CAS  Google Scholar 

  • Wiedeman LM, MacGregor A, Caldas C (1999) Analysis of the region of the 5′ end of the MLL gene involved in genomic duplication events. Brit J Haematol 105:256–264

    Article  Google Scholar 

  • Willmore E, Frank AJ, Padget K, Tilby MJ, Austin CA (1998) Etoposide targets topoisomerase II alpha and II beta in leukemic cells: isoform specific cleavage complexes visualized and quantified in situ by a novel immunofluorescence technique. Mol Pharmacol 54:78–85

    PubMed  CAS  Google Scholar 

  • Wu TC, Lichten M (1994) Meiosis-induced double strand break sites determined by yeast chromatin structure. Science 263:515–518

    Article  PubMed  CAS  Google Scholar 

  • Yang L, Rowe TC, Nelson EM, Liu LF (1985) In vivo mapping of DNA topoisomerase II specific cleavage sites on SV40 chromatin. Cell 41:127–132

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Strissel P, Strick R, Chen J, Nucifora G, Le Beau M, Larson RA, Rowley JD (2002) Genomic DNA breakpoints cluster in AML1/RUNX1 and ETO with topoisomerase II DNA cleavage and DNase I hypersensitive sites in t(8;21) leukemia. Proc Natl Acad Sci USA 99:3070–3075

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Zeleznik-Le N, Emmanuel N, Jayathilaka N, Chen J, Strissel P, Strick R, Li L, Neilly MB, Taki T, Hayashi et al (2004) Characterization of genomic breakpoints in MLL and CBP in leukemia patients with t(11;16). Genes Chromosomes Cancer 41:257–265

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors would like to dedicate this study to Dr. Hewson Swift, from the University of Chicago, deceased in 2004, who supported the idea that “chromatin matters” in chromosomal rearrangements. The authors would also like to thank Dr. Janet Rowley for her continued support with this study. This project was supported by ACS Grant # 01-06 to PLS and RS

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  1. Reiner Strick & Pamela L. Strissel

    Present address: Department of Obstetrics and Gynecology, University of Erlangen-Nuremberg, Laboratory for Molecular Medicine, Universitaetsstr. 21-23, 91054, Erlangen, Germany

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  1. Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA

    Reiner Strick, Yanming Zhang, Neelmini Emmanuel & Pamela L. Strissel

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Strick, R., Zhang, Y., Emmanuel, N. et al. Common chromatin structures at breakpoint cluster regions may lead to chromosomal translocations found in chronic and acute leukemias. Hum Genet 119, 479–495 (2006). https://doi.org/10.1007/s00439-006-0146-9

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