PAX5 is a tumor suppressor in mouse mutagenesis models of acute lymphoblastic leukemia

Blood

Volumn 125, Issue 23, 2015, Pages 3609-3617

  Dang, Jinjun ^a   Wei, Lei ^a,g   De Ridder, Jeroen ^b   Su, Xiaoping ^a,f   Rust, Alistair G ^c,e   Roberts, Kathryn G ^a   Payne Turner, Debbie ^a   Cheng, Jinjun ^a   Ma, Jing ^a   Qu, Chunxu ^a   Wu, Gang ^a   Song, Guangchun ^a   Huether, Robert G ^a,d   Schulman, Brenda ^a   Janke, Laura ^a   Zhang, Jinghui ^a   Downing, James R ^a   Van Der Weyden, Louise ^a   Adams, David J ^a   Mullighan, Charles G ^a  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^b Department of Microelectronics   (Netherlands)

^c WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^d AMBRY GENETICS   (United States)

^e INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^f UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^g ROSWELL PARK CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 CHLORO N2 [1 (5 FLUORO 2 PYRIMIDINYL)ETHYL] N4 (5 METHYL 1H PYRAZOL 3 YL) 2,4 PYRIMIDINEDIAMINE; JANUS KINASE 1; JANUS KINASE 3; RAS PROTEIN; RUXOLITINIB; TRANSCRIPTION FACTOR PAX5; PAX5 PROTEIN, MOUSE; TUMOR SUPPRESSOR PROTEIN;

ACUTE LYMPHOBLASTIC LEUKEMIA; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CHROMOSOME 15; COMPARATIVE GENOMIC HYBRIDIZATION; CONTROLLED STUDY; DNA BINDING; EXOME; EXON; GENE DOSAGE; GENE EXPRESSION; HAPLOINSUFFICIENCY; HETEROZYGOSITY; IMMUNOHISTOCHEMISTRY; IMMUNOPHENOTYPING; INTRON; LATENT PERIOD; LEUKEMOGENESIS; LOSS OF FUNCTION MUTATION; MISSENSE MUTATION; MOUSE; MUTAGENESIS; NONHUMAN; PATHOGENESIS; PENETRANCE; PHENOTYPE; PRE B LYMPHOCYTE; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA SEQUENCE; SIGNAL TRANSDUCTION; SOMATIC MUTATION; TRANSCRIPTION INITIATION; WILD TYPE; ANIMAL; EXPERIMENTAL NEOPLASM; GENE DELETION; GENETICS; METABOLISM; MUTANT MOUSE STRAIN; PATHOLOGY;

ANIMALS; B-CELL-SPECIFIC ACTIVATOR PROTEIN; GENE DELETION; MICE; MICE, MUTANT STRAINS; NEOPLASMS, EXPERIMENTAL; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; TUMOR SUPPRESSOR PROTEINS;

EID: 84930934045     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2015-02-626127     Document Type: Article

References (62)

1. Inaba H, Greaves M, Mullighan CG. Acute lymphoblastic leukaemia. Lancet. 2013; 381(9881):1943-1955.
2. Mullighan CG. Genomic characterization of childhood acute lymphoblastic leukemia. Semin Hematol. 2013;50(4):314-324.
3. Mullighan CG, Goorha S, Radtke I, et al. Genomewide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature. 2007; 446(7137):758-764.
4. Mullighan CG, Su X, Zhang J, et al Children's Oncology Group. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009;360(5):470-480.
5. Nebral K, Denk D, Attarbaschi A, et al. Incidence and diversity of PAX5 fusion genes in childhood acute lymphoblastic leukemia. Leukemia. 2009; 23(1):134-143.
6. Liu GJ, Cimmino L, Jude JG, et al. Pax5 loss imposes a reversible differentiation block in B-progenitor acute lymphoblastic leukemia. Genes Dev. 2014;28(12):1337-1350.
7. Heltemes-Harris LM, Willette MJ, Ramsey LB, et al. Ebf1 or Pax5 haploinsufficiency synergizes with STAT5 activation to initiate acute lymphoblastic leukemia. J Exp Med. 2011;208(6): 1135-1149.
8. Roubinian JR, Papoian R, Talal N. Effects of neonatal thymectomy and splenectomy on survival and regulation of autoantibody formation in NZB/NZW F1 mice. J Immunol. 1977;118(5): 1524-1529.
9. Urbánek P, Wang ZQ, Fetka I, Wagner EF, Busslinger M. Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAP. Cell. 1994;79(5):901-912.
10. Wolff L, Koller R, Hu X, Anver MR. A Moloney murine leukemia virus-based retrovirus with 4070A long terminal repeat sequences induces a high incidence of myeloid as well as lymphoid neoplasms. J Virol. 2003;77(8):4965-4971.
11. Hardy RR, Hayakawa K. B cell development pathways. Annu Rev Immunol. 2001;19:595-621.
12. Mullighan CG, Miller CB, Radtke I, et al. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature. 2008;453(7191): 110-114.
13. Olshen AB, Venkatraman ES, Lucito R, Wigler M. Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics. 2004;5(4):557-572.
14. Gentleman RC, Carey VJ, Bates DM, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004;5(10):R80.
15. Zhang J, Wheeler DA, Yakub I, et al. SNPdetector: a software tool for sensitive and accurate SNP detection. PLOS Comput Biol. 2005;1(5):e53.
16. Holmfeldt L, Wei L, Diaz-Flores E, et al. The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nat Genet. 2013;45(3): 242-252.
17. Keane TM, Goodstadt L, Danecek P, et al. Mouse genomic variation and its effect on phenotypes and gene regulation. Nature. 2011;477(7364): 289-294.
18. Sherry ST, Ward MH, Kholodov M, et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2001;29(1):308-311.
19. Zhang J, Ding L, Holmfeldt L, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012;481(7380):157-163.
20. Uren AG, Mikkers H, Kool J, et al. A high-throughput splinkerette-PCR method for the isolation and sequencing of retroviral insertion sites. Nat Protoc. 2009;4(5):789-798.
21. de Ridder J, Uren A, Kool J, Reinders M, Wessels L. Detecting statistically significant common insertion sites in retroviral insertional mutagenesis screens. PLOS Comput Biol. 2006;2(12):e166.
22. Suzuki T, Shen H, Akagi K, et al. New genes involved in cancer identified by retroviral tagging. Nat Genet. 2002;32(1):166-174.
23. Collier LS, Carlson CM, Ravimohan S, Dupuy AJ, Largaespada DA. Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature. 2005; 436(7048):272-276.
24. Schrödinger L. The PyMOL Molecular Graphics System, Version 1.7.4 Schrödinger, LLC.
25. Garvie CW, Hagman J, Wolberger C. Structural studies of Ets-1/Pax5 complex formation on DNA. Mol Cell. 2001;8(6):1267-1276.
26. Xu HE, Rould MA, Xu W, Epstein JA, Maas RL, Pabo CO. Crystal structure of the human Pax6 paired domain-DNA complex reveals specific roles for the linker region and carboxy-terminal subdomain in DNA binding. Genes Dev. 1999; 13(10):1263-1275.
27. Bandaranayake RM, Ungureanu D, Shan Y, Shaw DE, Silvennoinen O, Hubbard SR. Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F. Nat Struct Mol Biol. 2012;19(8):754-759.
28. Mullighan CG, Zhang J, Harvey RC, et al. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci USA. 2009;106(23):9414-9418.
29. Hedvat M, Huszar D, Herrmann A, et al. The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell. 2009;16(6):487-497.
30. Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010;363(12):1117-1127.
31. Tseng YY, Moriarity BS, Gong W, et al. PVT1 dependence in cancer with MYC copy-number increase. Nature. 2014;512(7512):82-86.
32. Bamford S, Dawson E, Forbes S, et al. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br J Cancer. 2004;91(2):355-358.
33. Mullighan CG, Zhang J, Kasper LH, et al. CREBBP mutations in relapsed acute lymphoblastic leukaemia. Nature. 2011; 471(7337):235-239.
34. Roberts KG, Morin RD, Zhang J, et al. Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia. Cancer Cell. 2012;22(2):153-166.
35. Zhang J, Mullighan CG, Harvey RC, 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(11):3080-3087.
36. Shah S, Schrader KA, Waanders E, et al. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia. Nat Genet. 2013;45(10):1226-1231.
37. Gruber TA, Larson Gedman A, Zhang J, et al. An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia. Cancer Cell. 2012;22(5):683-697.
38. Roberts KG, Li Y, Payne-Turner D, et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014;371(11):1005-1015.
39. Bains T, Heinrich MC, Loriaux MM, et al. Newly described activating JAK3 mutations in T-cell acute lymphoblastic leukemia. Leukemia. 2012; 26(9):2144-2146.
40. Neumann M, Greif PA, Baldus CD. Mutational landscape of adult ETP-ALL. Oncotarget. 2013; 4(7):954-955.
41. Degryse S, de Bock CE, Cox L, et al. JAK3 mutants transform hematopoietic cells through JAK1 activation, causing T-cell acute lymphoblastic leukemia in a mouse model. Blood. 2014;124(20):3092-3100.
42. Atak ZK, Gianfelici V, Hulselmans G, et al. Comprehensive analysis of transcriptome variation uncovers known and novel driver events in T-cell acute lymphoblastic leukemia. PLoS Genet. 2013;9(12):e1003997.
43. De Keersmaecker K, Atak ZK, Li N, et al. Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia. Nat Genet. 2013;45(2): 186-190.
44. Akagi K, Suzuki T, Stephens RM, Jenkins NA, Copeland NG. RTCGD: retroviral tagged cancer gene database. Nucleic Acids Res. 2004; 32(Database issue):D523-D527.
45. Mullighan CG, Collins-Underwood JR, Phillips LA, et al. Rearrangement of CRLF2 in B-progenitor-and Down syndrome-associated acute lymphoblastic leukemia. Nat Genet. 2009;41(11): 1243-1246.
46. Papaemmanuil E, Rapado I, Li Y, et al. RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia. Nat Genet. 2014; 46(2):116-125.
47. Bercovich D, Ganmore I, Scott LM, et al. Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome. Lancet. 2008;372(9648):1484-1492.
48. Shochat C, Tal N, Bandapalli OR, et al. Gain-of-function mutations in interleukin-7 receptor-α (IL7R) in childhood acute lymphoblastic leukemias. J Exp Med. 2011;208(5):901-908.
49. Shochat C, Tal N, Gryshkova V, et al. Novel activating mutations lacking cysteine in type I cytokine receptors in acute lymphoblastic leukemia. Blood. 2014;124(1):106-110.
50. Kuiper RP, Schoenmakers EF, van Reijmersdal SV, et al. High-resolution genomic profiling of childhood ALL reveals novel recurrent genetic lesions affecting pathways involved in lymphocyte differentiation and cell cycle progression. Leukemia. 2007;21(6):1258-1266.
51. Kontro M, Kuusanmäki H, Eldfors S, et al. Novel activating STAT5B mutations as putative drivers of T-cell acute lymphoblastic leukemia. Leukemia. 2014;28(8):1738-1742.
52. Goossens S, Radaelli E, Blanchet O, et al. ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling. Nat Commun. 2015;6:5794.
53. Tzoneva G, Perez-Garcia A, Carpenter Z, et al. Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL. Nat Med. 2013;19(3):368-371.
54. Lahortiga I, De Keersmaecker K, Van Vlierberghe P, et al. Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia. Nat Genet. 2007; 39(5):593-595.
55. Jeong EG, Kim MS, Nam HK, et al. Somatic mutations of JAK1 and JAK3 in acute leukemias and solid cancers. Clin Cancer Res. 2008;14(12): 3716-3721.
56. Flex E, Petrangeli V, Stella L, et al. Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia. J Exp Med. 2008;205(4): 751-758.
57. Abaan OD, Polley EC, Davis SR, et al. The exomes of the NCI-60 panel: a genomic resource for cancer biology and systems pharmacology. Cancer Res. 2013;73(14):4372-4382.
58. Neumann M, Vosberg S, Schlee C, et al. Mutational spectrum of adult T-ALL. Oncotarget. 2015;6(5):2754-2766.
59. Gutierrez A, Kentsis A, Sanda T, et al. The BCL11B tumor suppressor is mutated across the major molecular subtypes of T-cell acute lymphoblastic leukemia. Blood. 2011;118(15): 4169-4173.
60. Tartaglia M, Martinelli S, Cazzaniga G, et al. Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia. Blood. 2004;104(2): 307-313.
61. Irving J, Matheson E, Minto L, et al. Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition. Blood. 2014;124(23): 3420-3430.
62. Ma X, Edmonson M, Yergeau D, et al. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia. Nat Commun. 2015;6:6604.