Abstract
The κ deleting element (κDE) located 24 kb downstream of the Cκ gene segment mediates the deletion of Cκ and the Jκ-Cκ Intron enhancer, which results in allelic exclusion of the immunoglobulin κ light chain locus. We here report that the κDE can recombine to each recombination signal sequence (RSS) flanking Jκ1 to Jκ5 in normal hematopoiesis. Moreover, usage of the JκRSS-κDE junctional sequence allows the detection of minimal residual disease in acute lymphoblastic leukemia.
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References
Korsmeyer SJ, Hieter PA, Ravetch JV, Poplack DG, Waldmann TA, Leder P . Developmental hierarchy of immunological gene rearrangements in human leukemic pre-B cells Proc Natl Acad Sci USA 1981 78: 7096–7100
Hieter PA, Korsmeyer SJ, Waldmann TA, Leder P . Human immunoglobulin κ light-chain genes are deleted or rearranged in λ-producing B cells Nature 1981 290: 368–372
Siminovitch KA, Bakhshi A, Goldman P, Korsmeyer SG . A uniform deleting element mediates the loss of κ genes in human B cells Nature 1985 316: 260–262
Klobeck H-G, Zachau HG . The human Cκ gene segment and the kappa deleting element are closely linked Nucleic Acids Res 1988 14: 4591–4603
Graninger WB, Goldman PL, Morton CC, O'Brien SJ, Korsmeyer SJ . The kappa-deleting element. Germline and rearranged, duplicated and dispersed forms J Exp Med 1988 167: 488–501
Schäble KF, Zachau HG . The variable genes of the human immunoglobulin κ locus Biol Chem Hoppe-Seyler 1993 374: 1001–1022
Feddersen RM, Martin DJ, van Ness BG . Novel recombinations in the Ig κ-locus that result in allelic exclusion J Immunol 1990 145: 745–750
Beishuizen A, Verhoeven MAJ, Mol EJ, van Dongen JJM . Detection of immunoglobulin kappa light-chain gene rearrangement patterns by Southern blot analysis Leukemia 1994 8: 2228–2236
Beishuizen A, de Bruijn MAC, Pongers-Willemse MJ, Verhoeven MAJ, van Wering ER, Hählen K, Breit TM, de Bruin-Versteeg S, Hooijkaas H, van Dongen JJM . Heterogeneity in junctional regions of immunoglobulin kappa deleting element rearrangements in B cell leukemias: a new molecular target for detection of minimal residual disease Leukemia 1997 11: 2200–2207
Van Dongen JJM, Seriu T, Panzer-Grumayer ER, Biondi A, Pongers-Willemse MJ, Corral L, Stolz F, Schrappe M, Masera G, Kamps WA, Gadner H, van Wering ER, Ludwig W-D, Basso G, de Bruijn MAC, Cazzaniga G, Hettinger K, van der Does-van den Berg A, Hop WCJ, Riehm H, Bartram CR . Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood Lancet 1998 352: 1731–1738
Pongers-Willemse MJ, Seriu T, Stolz F, Corral L, Gameiro P, Pisa P, Gonzales M, Bartram CR, Panzer-Grumayer ER, Biondi A, San Miguel JF, van Dongen JJM . Primers and protocols for standardized MRD detection in ALL using immunoglobulin and T cell receptor gene rearrangements and TAL1 deletions as PCR targets Leukemia 1999 13: 110–118
Ludwig W-D, Bartram CR, Ritter J, Raghavachar A, Hiddemann W, Heil G, Harbott J, Seibt-Jung H, Teichmann JV, Riehm H . Ambiguous phenotypes and genotypes in 16 children with acute leukemia as characterized by multiparameter analysis Blood 1988 71: 1518–1528
van der Does-van der Berg A, Bartram CR, Basso G, Benoit YCM, Biondi A, Debatin KM, Haas OA, Harbott J, Kamps WA, Köller U, Lampert F, Ludwig W-D, Niemeyer CM, van Wering ER . Minimal requirements for the diagnosis, classification and evaluation of the treatment of childhood acute lymphoblastic leukemia (ALL) in the ‘BFM family’ cooperative group Med Ped Oncol 1992 20: 497–505
Yokota S, Hansen-Hagge TE, Ludwig WD, Reiter A, Raghavachar A, Kleihauer E, Bartram CR . Use of polymerase chain reactions to monitor minimal residual disease in acute lymphoblastic leukemia patients Blood 1991 77: 331–339
van Dongen JJM, Wolvers-Tettero ILM . Analysis of immunoglobulin and T-cell receptor genes. Part I: basic and technical aspects Clin Chim Acta 1991 198: 1–91
Seriu T, Hansen-Hagge TE, Erz DHR, Bartram CR . Improved detection of minimal residual leukemia through modifications of polymerase chain reaction analyses based on clonospecific T cell receptor junctions Leukemia 1995 9: 316–320
Lewis SM, Hesse JE, Mizuuchi K, Gellert M . Novel strand exchanges in V(D)J recombination Cell 1988 55: 1099–1107
Lewis SM . The mechanism of V(D)J joining: lessons from molecular, immunological and comparative analysis Adv Immunol 1994 56: 27–150
Bogue M, Roth DB . Mechanism of V(D)J recombination Curr Opin Immunol 1996 8: 175–180
Whitehurst C, Henney HR, Max EE, Schroeder Jr HW, Stüber F, Siminovitch KA, Garrard WT . Nucleotide sequence of the intron of the germline human κ immunoglobulin gene connecting the J and C regions reveals a matrix association region (MAR) next to the enhancer Nucleic Acids Res 1992 20: 4929–4930
Xu Y, Davidson L, Alt FW, Baltimore D . Deletion of the Ig kappa light chain intronic enhancer/matrix attachment region impairs but does not abolish VκJκ rearrangement Immunity 1996 4: 377–385
Acknowledgements
This work was supported by grants from the Deutsche Krebshilfe and the Deutsche Forschungsgemeinschaft to CRB. The authors gratefully acknowledge Prof W-D Ludwig for immunophenotype analysis, Dr S Yokota and Dr JWG Janssen for helpful discussions, D Erz for technical assistance, A Jordan for secretarial help, and the participants of the German ALL-BFM Study Group for their continuous cooperation.
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Seriu, T., Hansen-Hagge, T., Stark, Y. et al. Immunoglobulin κ gene rearrangements between the κ deleting element and Jκ recombination signal sequences in acute lymphoblastic leukemia and normal hematopoiesis. Leukemia 14, 671–674 (2000). https://doi.org/10.1038/sj.leu.2401745
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DOI: https://doi.org/10.1038/sj.leu.2401745
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