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VPREB1 deletions occur independent of lambda light chain rearrangement in childhood acute lymphoblastic leukemia

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References

  1. Loh ML, Mullighan CG . Advances in the genetics of high-risk childhood B-progenitor acute lymphoblastic leukemia and juvenile myelomonocytic leukemia: implications for therapy. Clin Cancer Res 2012; 18: 2754–2767.

    CAS  PubMed  Google Scholar 

  2. Den Boer ML, van Slegtenhorst M, De Menezes RX, Cheok MH, Buijs-Gladdines JG, Peters ST et al. A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study. Lancet Oncol 2009; 10: 125–134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 2007; 446: 758–764.

    CAS  PubMed  Google Scholar 

  4. Harvey RC, Mullighan CG, Wang X, Dobbin KK, Davidson GS, Bedrick EJ et al. Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome. Blood 2010; 116: 4874–4884.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Trageser D, Iacobucci I, Nahar R, Duy C, von Levetzow G, Klemm L et al. Pre-B cell receptor-mediated cell cycle arrest in Philadelphia chromosome-positive acute lymphoblastic leukemia requires IKAROS function. J Exp Med 2009; 206: 1739–1753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. van Delft FW, Horsley S, Colman S, Anderson K, Bateman C, Kempski H et al. Clonal origins of relapse in ETV6-RUNX1 acute lymphoblastic leukemia. Blood 2011; 117: 6247–6254.

    Article  CAS  PubMed  Google Scholar 

  7. Hertzberg L, Vendramini E, Ganmore I, Cazzaniga G, Schmitz M, Chalker J et al. Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group. Blood 2010; 115: 1006–1017.

    Article  CAS  PubMed  Google Scholar 

  8. Kuster L, Grausenburger R, Fuka G, Kaindl U, Krapf G, Inthal A et al. ETV6/RUNX1-positive relapses evolve from an ancestral clone and frequently acquire deletions of genes implicated in glucocorticoid signaling. Blood 2011; 117: 2658–2667.

    Article  CAS  PubMed  Google Scholar 

  9. Buitenkamp TD, Pieters R, Gallimore NE, van der Veer A, Meijerink JP, Beverloo HB et al. Outcome in children with Down's syndrome and acute lymphoblastic leukemia: role of IKZF1 deletions and CRLF2 aberrations. Leukemia 2012; 26: 2204–2211.

    Article  CAS  PubMed  Google Scholar 

  10. Zhang J, Mullighan CG, Harvey RC, Wu G, Chen X, Edmonson M et al. Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood 2011; 118: 3080–3087.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bowman WP, Larsen EL, Devidas M, Linda SB, Blach L, Carroll AJ et al. Augmented therapy improves outcome for pediatric high risk acute lymphocytic leukemia: results of Children's Oncology Group trial P9906. Pediatr Blood Cancer 2011; 57: 569–577.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Mullighan CG, Su X, Zhang J, Radtke I, Phillips LA, Miller CB et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med 2009; 360: 470–480.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Schiffman JD, Lorimer PD, Rodic V, Jahromi MS, Downie JM, Bayerl MG et al. Genome wide copy number analysis of paediatric Burkitt lymphoma using formalin-fixed tissues reveals a subset with gain of chromosome 13q and corresponding miRNA over expression. Br J Haematol 2011; 155: 477–486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Brauninger A, Goossens T, Rajewsky K, Kuppers R . Regulation of immunoglobulin light chain gene rearrangements during early B cell development in the human. Eur J Immunol 2001; 31: 3631–3637.

    Article  CAS  PubMed  Google Scholar 

  15. Korsmeyer SJ, Hieter PA, Sharrow SO, Goldman CK, Leder P, Waldmann TA . Normal human B cells display ordered light chain gene rearrangements and deletions. J Exp Med 1982; 156: 975–985.

    Article  CAS  PubMed  Google Scholar 

  16. Hogan LE, Meyer JA, Yang J, Wang J, Wong N, Yang W et al. Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies. Blood 2011; 118: 5218–5226.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Mullighan CG, Downing JR . Genome-wide profiling of genetic alterations in acute lymphoblastic leukemia: recent insights and future directions. Leukemia 2009; 23: 1209–1218.

    Article  CAS  PubMed  Google Scholar 

  18. Herzog S, Reth M, Jumaa H . Regulation of B-cell proliferation and differentiation by pre-B-cell receptor signalling. Nat Rev Immunol 2009; 9: 195–205.

    Article  CAS  PubMed  Google Scholar 

  19. Minegishi Y, Coustan-Smith E, Wang YH, Cooper MD, Campana D, Conley ME . Mutations in the human lambda5/14.1 gene result in B cell deficiency and agammaglobulinemia. J Exp Med 1998; 187: 71–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Shimizu T, Mundt C, Licence S, Melchers F, Martensson IL . VpreB1/VpreB2/lambda 5 triple-deficient mice show impaired B cell development but functional allelic exclusion of the IgH locus. J Immunol 2002; 168: 6286–6293.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

JDS was supported by American Society of Hematology (ASH) Scholar Award, CureSearch Foundation Award, Cancer and Control Population Sciences Pilot Award from Huntsman Cancer Institute, and is the Edward B Clark, MD Chair in Pediatric Research. DSM was supported by Albert Einstein School of Medicine Student Exchange Program. SPH is the Ergen Family Chair in Pediatric Cancer. CGM is Pew Scholar in the Biomedical Sciences and a St Baldrick's Scholar. MM is a Scholar of the Leukemia and Lymphoma Society and a Senior Investigator of the Wellcome Trust. This work was also supported by grants to the COG including the COG Chair’s grant (CA98543) and a supplement to support the TARGET Project, U10 CA98413 (COG Statistical Center) and U24 CA114766 (COG Specimen Banking), and the American Lebanese Syrian Associated Charities of St Jude Children’s Research Hospital.

AUTHOR CONTRIBUTIONS

DSM, JD, CCM, MM, NM, NT, JKF, RCH, SPH, JJY, PB, CGM, RRM, and JDS wrote the paper. DSM, JD, CCM, MSJ, JJY, RRM, and JDS designed and performed research. MM and SPH contributed reagents, cell lines and/or samples. CLW, RCH, SPH, JJY, CGM contributed genomic data.

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Correspondence to J D Schiffman.

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JDS is a scientific consultant for Affymetrix, Inc. The remaining authors declare no conflict of interest.

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Supplementary Information accompanies this paper on the Leukemia website

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Mangum, D., Downie, J., Mason, C. et al. VPREB1 deletions occur independent of lambda light chain rearrangement in childhood acute lymphoblastic leukemia. Leukemia 28, 216–220 (2014). https://doi.org/10.1038/leu.2013.223

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