AID expression in B-cell lymphomas causes accumulation of genomic uracil and a distinct AID mutational signature

DNA Repair

Volumn 25, Issue , 2015, Pages 60-71

  Pettersen, Henrik Sahlin ^a,b   Galashevskaya, Anastasia ^a   Doseth, Berit ^a   Sousa, Mirta M L ^a   Sarno, Antonio ^a   Visnes, Torkild ^a,c   Aas, Per Arne ^a   Liabakk, Nina Beate ^a   Slupphaug, Geir ^a   Sætrom, Pål ^a   Kavli, Bodil ^a   Krokan, Hans E ^a  

^a NORWEGIAN UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Norway)

^b TRONDHEIM UNIVERSITY HOSPITAL   (Norway)

^c SCIENCE FOR LIFE LABORATORY   (Sweden)

Author keywords

Activation induced cytidine deaminase (AID); B cell lymphoma; Base excision repair; Genomic uracil; Kataegis; Mutational signature

Indexed keywords

ACTIVATION INDUCED CYTIDINE DEAMINASE; APOLIPOPROTEIN B MESSENGER RNA EDITING ENZYME CATALYTIC POLYPEPTIDE 1; DEOXYURIDINE; DNA; URACIL; URACIL DNA GLYCOSIDASE; AICDA (ACTIVATION-INDUCED CYTIDINE DEAMINASE); CYTIDINE DEAMINASE; CYTOSINE; SMUG1 PROTEIN, HUMAN;

ANIMAL CELL; ARTICLE; B CELL LYMPHOMA; B-CELL LYMPHOMA CELL LINE; CHRONIC LYMPHATIC LEUKEMIA; CONTROLLED STUDY; DEAMINATION; DNA REPAIR; FEMALE; GENE MUTATION; GENE SILENCING; GENOMICS; HELA CELL LINE; HUMAN; HUMAN CELL; LYMPHOMA; MOUSE; MULTIGENE FAMILY; MUTAGENESIS; NONHUMAN; PROTEIN EXPRESSION; SOMATIC MUTATION; TANDEM MASS SPECTROMETRY; BASE MISPAIRING; ENZYMOLOGY; GENE REARRANGEMENT; GENETICS; METABOLISM; MUTATION; POINT MUTATION; TUMOR CELL LINE;

BASE PAIR MISMATCH; CELL LINE, TUMOR; CYTIDINE DEAMINASE; CYTOSINE; DEAMINATION; DNA REPAIR; DNA, NEOPLASM; GENE KNOCKDOWN TECHNIQUES; HUMANS; IMMUNOGLOBULIN CLASS SWITCHING; LYMPHOMA, B-CELL; MUTATION; POINT MUTATION; URACIL; URACIL-DNA GLYCOSIDASE;

EID: 84918779420     PISSN: 15687864     EISSN: 15687856     Source Type: Journal    
DOI: 10.1016/j.dnarep.2014.11.006     Document Type: Article

References (70)

1. Kavli B., Otterlei M., Slupphaug G., Krokan H.E. Uracil in DNA-general mutagen, but normal intermediate in acquired immunity. DNA Repair 2007, 6:505-516.
2. Muramatsu M., Sankaranand V.S., Anant S., Sugai M., Kinoshita K., Davidson N.O., Honjo T. Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells. J. Biol. Chem. 1999, 274:18470-18476.
3. Petersen-Mahrt S.K., Harris R.S., Neuberger M.S. AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature 2002, 418:99-103.
4. Di Noia J., Neuberger M.S. Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase. Nature 2002, 419:43-48.
5. Imai K., Slupphaug G., Lee W.I., Revy P., Nonoyama S., Catalan N., Yel L., Forveille M., Kavli B., Krokan H.E., Ochs H.D., Fischer A., Durandy A. Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. Nat. Immunol. 2003, 4:1023-1028.
6. Rada C., Williams G.T., Nilsen H., Barnes D.E., Lindahl T., Neuberger M.S. Immunoglobulin isotype switching is inhibited and somatic hypermutation perturbed in UNG-deficient mice. Curr. Biol.: CB 2002, 12:1748-1755.
7. Conticello S.G. The AID/APOBEC family of nucleic acid mutators. Genome Biol. 2008, 9:229.
8. Harris R.S., Petersen-Mahrt S.K., Neuberger M.S. RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators. Mol. Cell. 2002, 10:1247-1253.
9. Zhang J., Grubor V., Love C.L., Banerjee A., Richards K.L., Mieczkowski P.A., Dunphy C., Choi W., Au W.Y., Srivastava G., Lugar P.L., Rizzieri D.A., Lagoo A.S., Bernal-Mizrachi L., Mann K.P., Flowers C., Naresh K., Evens A., Gordon L.I., Czader M., Gill J.I., Hsi E.D., Liu Q., Fan A., Walsh K., Jima D., Smith L.L., Johnson A.J., Byrd J.C., Luftig M.A., Ni T., Zhu J., Chadburn A., Levy S., Dunson D., Dave S.S. Genetic heterogeneity of diffuse large B-cell lymphoma. Proc. Natl. Acad. Sci. U.S.A. 2013, 110:1398-1403.
10. Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Patterns of somatic mutation in human cancer genomes. Nature 2007, 446:153-158.
11. Alexandrov L.B., Nik-Zainal S., Wedge D.C., Aparicio S.A., Behjati S., Biankin A.V., Bignell G.R., Bolli N., Borg A., Borresen-Dale A.L., Boyault S., Burkhardt B., Butler A.P., Caldas C., Davies H.R., Desmedt C., Eils R., Eyfjord J.E., Foekens J.A., Greaves M., Hosoda F., Hutter B., Ilicic T., Imbeaud S., Imielinski M., Jager N., Jones D.T., Jones D., Knappskog S., Kool M., Lakhani S.R., Lopez-Otin C., Martin S., Munshi N.C., Nakamura H., Northcott P.A., Pajic M., Papaemmanuil E., Paradiso A., Pearson J.V., Puente X.S., Raine K., Ramakrishna M., Richardson A.L., Richter J., Rosenstiel P., Schlesner M., Schumacher T.N., Span P.N., Teague J.W., Totoki Y., Tutt A.N., Valdes-Mas R., van Buuren M.M., van't Veer L., Vincent-Salomon A., Waddell N., Yates L.R., Australian Pancreatic Cancer Genome I., Consortium I.B.C., Consortium I.M.-S., PedBrain I., Zucman-Rossi J., Futreal P.A., McDermott U., Lichter P., Meyerson M., Grimmond S.M., Siebert R., Campo E., Shibata T., Pfister S.M., Campbell P.J., Stratton M.R. Signatures of mutational processes in human cancer. Nature 2013, 500:415-421.
12. Hu Y., Ericsson I., Torseth K., Methot S.P., Sundheim O., Liabakk N.B., Slupphaug G., Di Noia J.M., Krokan H.E., Kavli B. A combined nuclear and nucleolar localization motif in activation-induced cytidine deaminase (AID) controls immunoglobulin class switching. J. Mol. Biol. 2013, 425:424-443.
13. Hagen L., Kavli B., Sousa M.M., Torseth K., Liabakk N.B., Sundheim O., Pena-Diaz J., Otterlei M., Horning O., Jensen O.N., Krokan H.E., Slupphaug G. Cell cycle-specific UNG2 phosphorylations regulate protein turnover, activity and association with RPA. EMBO J. 2008, 27:51-61.
14. Visnes T., Akbari M., Hagen L., Slupphaug G., Krokan H.E. The rate of base excision repair of uracil is controlled by the initiating glycosylase. DNA Repair 2008, 7:1869-1881.
15. Galashevskaya A., Sarno A., Vagbo C.B., Aas P.A., Hagen L., Slupphaug G., Krokan H.E. A robust, sensitive assay for genomic uracil determination by LC/MS/MS reveals lower levels than previously reported. DNA Repair 2013, 12:699-706.
16. Kavli B., Sundheim O., Akbari M., Otterlei M., Nilsen H., Skorpen F., Aas P.A., Hagen L., Krokan H.E., Slupphaug G. hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup. J. Biol. Chem. 2002, 277:39926-39936.
17. Akbari M., Otterlei M., Pena-Diaz J., Aas P.A., Kavli B., Liabakk N.B., Hagen L., Imai K., Durandy A., Slupphaug G., Krokan H.E. Repair of U/G and U/A in DNA by UNG2-associated repair complexes takes place predominantly by short-patch repair both in proliferating and growth-arrested cells. Nucleic Acids Res. 2004, 32:5486-5498.
18. Batth T.S., Keasling J.D., Petzold C.J. Targeted proteomics for metabolic pathway optimization. Methods Mol. Biol. 2012, 944:237-249.
19. MacLean B., Tomazela D.M., Shulman N., Chambers M., Finney G.L., Frewen B., Kern R., Tabb D.L., Liebler D.C., MacCoss M.J. Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics 2010, 26:966-968.
20. Maul R.W., Saribasak H., Martomo S.A., McClure R.L., Yang W., Vaisman A., Gramlich H.S., Schatz D.G., Woodgate R., Wilson D.M., 3rd P.J., Gearhart Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions. Nat. Immunol. 2011, 12:70-76.
21. Greeve J., Philipsen A., Krause K., Klapper W., Heidorn K., Castle B.E., Janda J., Marcu K.B., Parwaresch R. Expression of activation-induced cytidine deaminase in human B-cell non-Hodgkin lymphomas. Blood 2003, 101:3574-3580.
22. Smit L.A., Bende R.J., Aten J., Guikema J.E., Aarts W.M., van Noesel C.J. Expression of activation-induced cytidine deaminase is confined to B-cell non-Hodgkin's lymphomas of germinal-center phenotype. Cancer Res. 2003, 63:3894-3898.
23. Lossos I.S., Levy R., Alizadeh A.A. AID is expressed in germinal center B-cell-like and activated B-cell-like diffuse large-cell lymphomas and is not correlated with intraclonal heterogeneity. Leukemia 2004, 18:1775-1779.
24. Pasqualucci L., Guglielmino R., Houldsworth J., Mohr J., Aoufouchi S., Polakiewicz R., Chaganti R.S., Dalla-Favera R. Expression of the AID protein in normal and neoplastic B cells. Blood 2004, 104:3318-3325.
25. Gallien S., Duriez E., Crone C., Kellmann M., Moehring T., Domon B. Targeted proteomic quantification on quadrupole-orbitrap mass spectrometer. Mol. Cell. Proteomics: MCP 2012, 11:1709-1723.
26. Peterson A.C., Russell J.D., Bailey D.J., Westphall M.S., Coon J.J. Parallel reaction monitoring for high resolution and high mass accuracy quantitative, targeted proteomics. Mol. Cell. Proteomics: MCP 2012, 11:1475-1488.
27. Hu Y., Ericsson I., Doseth B., Liabakk N.B., Krokan H.E., Kavli B. Activation-induced cytidine deaminase (AID) is localized to subnuclear domains enriched in splicing factors. Exp. Cell Res. 2014, 322:178-192.
28. Krokan H.E., Bjoras M. Base excision repair. Cold Spring Harbor Perspect. Biol. 2013, 5:a012583.
29. Pettersen H.S., Sundheim O., Gilljam K.M., Slupphaug G., Krokan H.E., Kavli B. Uracil-DNA glycosylases SMUG1 and UNG2 coordinate the initial steps of base excision repair by distinct mechanisms. Nucleic Acids Res. 2007, 35:3879-3892.
30. Yamane A., Resch W., Kuo N., Kuchen S., Li Z., Sun H.W., Robbiani D.F., McBride K., Nussenzweig M.C., Casellas R. Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes. Nat. Immunol. 2011, 12:62-69.
31. Liu M., Duke J.L., Richter D.J., Vinuesa C.G., Goodnow C.C., Kleinstein S.H., Schatz D.G. Two levels of protection for the B cell genome during somatic hypermutation. Nature 2008, 451:841-845.
32. Hasham M.G., Donghia N.M., Coffey E., Maynard J., Snow K.J., Ames J., Wilpan R.Y., He Y., King B.L., Mills K.D. Widespread genomic breaks generated by activation-induced cytidine deaminase are prevented by homologous recombination. Nat. Immunol. 2010, 11:820-826.
33. Nilsen H., Otterlei M., Haug T., Solum K., Nagelhus T.A., Skorpen F., Krokan H.E. Nuclear and mitochondrial uracil-DNA glycosylases are generated by alternative splicing and transcription from different positions in the UNG gene. Nucleic Acids Res. 1997, 25:750-755.
34. Nilsen H., Steinsbekk K.S., Otterlei M., Slupphaug G., Aas P.A., Krokan H.E. Analysis of uracil-DNA glycosylases from the murine Ung gene reveals differential expression in tissues and in embryonic development and a subcellular sorting pattern that differs from the human homologues. Nucleic Acids Res. 2000, 28:2277-2285.
35. Andersen S., Heine T., Sneve R., Konig I., Krokan H.E., Epe B., Nilsen H. Incorporation of dUMP into DNA is a major source of spontaneous DNA damage, while excision of uracil is not required for cytotoxicity of fluoropyrimidines in mouse embryonic fibroblasts. Carcinogenesis 2005, 26:547-555.
36. Ordinario E.C., Yabuki M., Larson R.P., Maizels N. Temporal regulation of Ig gene diversification revealed by single-cell imaging. J. Immunol. 2009, 183:4545-4553.
37. Sharbeen G., Yee C.W., Smith A.L., Jolly C.J. Ectopic restriction of DNA repair reveals that UNG2 excises AID-induced uracils predominantly or exclusively during G1 phase. J. Exp. Med. 2012, 209:965-974.
38. Schrader C.E., Guikema J.E., Linehan E.K., Selsing E., Stavnezer J. Activation-induced cytidine deaminase-dependent DNA breaks in class switch recombination occur during G1 phase of the cell cycle and depend upon mismatch repair. J. Immunol. 2007, 179:6064-6071.
39. Hardeland U., Kunz C., Focke F., Szadkowski M., Schar P. Cell cycle regulation as a mechanism for functional separation of the apparently redundant uracil DNA glycosylases TDG and UNG2. Nucleic Acids Res. 2007, 35:3859-3867.
40. Pena-Diaz J., Hegre S.A., Anderssen E., Aas P.A., Mjelle R., Gilfillan G.D., Lyle R., Drablos F., Krokan H.E., Saetrom P. Transcription profiling during the cell cycle shows that a subset of Polycomb-targeted genes is upregulated during DNA replication. Nucleic Acids Res. 2013, 41:2846-2856.
41. Akbari M., Pena-Diaz J., Andersen S., Liabakk N.B., Otterlei M., Krokan H.E. Extracts of proliferating and non-proliferating human cells display different base excision pathways and repair fidelity. DNA Repair 2009, 8:834-843.
42. Hardianti M.S., Tatsumi E., Syampurnawati M., Furuta K., Saigo K., Nakamachi Y., Kumagai S., Ohno H., Tanabe S., Uchida M., Yasuda N. Activation-induced cytidine deaminase expression in follicular lymphoma: association between AID expression and ongoing mutation in FL. Leukemia 2004, 18:826-831.
43. Bodor C., Bognar A., Reiniger L., Szepesi A., Toth E., Kopper L., Matolcsy A. Aberrant somatic hypermutation and expression of activation-induced cytidine deaminase mRNA in mediastinal large B-cell lymphoma. Br. J. Haematol. 2005, 129:373-376.
44. Deutsch A.J., Aigelsreiter A., Staber P.B., Beham A., Linkesch W., Guelly C., Brezinschek R.I., Fruhwirth M., Emberger W., Buettner M., Beham-Schmid C., Neumeister P. MALT lymphoma and extranodal diffuse large B-cell lymphoma are targeted by aberrant somatic hypermutation. Blood 2007, 109:3500-3504.
45. McCarthy H., Wierda W.G., Barron L.L., Cromwell C.C., Wang J., Coombes K.R., Rangel R., Elenitoba-Johnson K.S., Keating M.J., Abruzzo L.V. High expression of activation-induced cytidine deaminase (AID) and splice variants is a distinctive feature of poor-prognosis chronic lymphocytic leukemia. Blood 2003, 101:4903-4908.
46. Palacios F., Moreno P., Morande P., Abreu C., Correa A., Porro V., Landoni A.I., Gabus R., Giordano M., Dighiero G., Pritsch O., Oppezzo P. High expression of AID and active class switch recombination might account for a more aggressive disease in unmutated CLL patients: link with an activated microenvironment in CLL disease. Blood 2010, 115:4488-4496.
47. Yousif A.S., Stanlie A., Begum N.A., Honjo T. Opinion: uracil DNA glycosylase (UNG) plays distinct and non-canonical roles in somatic hypermutation and class switch recombination. Int. Immunol. 2014, 26:575-578.
48. Shalhout S., Haddad D., Sosin A., Holland T.C., Al-Katib A., Martin A., Bhagwat A.S. Genomic uracil homeostasis during normal B cell maturation and loss of this balance during B cell cancer development. Mol. Cell. Biol. 2014, 34:4019-4032.
49. Roche B., Claes A., Rougeon F. Deoxyuridine triphosphate incorporation during somatic hypermutation of mouse VkOx genes after immunization with phenyloxazolone. J. Immunol. 2010, 185:4777-4782.
50. Crouch E.E., Li Z., Takizawa M., Fichtner-Feigl S., Gourzi P., Montano C., Feigenbaum L., Wilson P., Janz S., Papavasiliou F.N., Casellas R. Regulation of AID expression in the immune response. J. Exp. Med. 2007, 204:1145-1156.
51. Han J.H., Akira S., Calame K., Beutler B., Selsing E., Imanishi-Kari T. Class switch recombination and somatic hypermutation in early mouse B cells are mediated by B cell and Toll-like receptors. Immunity 2007, 27:64-75.
52. Pasqualucci L., Bhagat G., Jankovic M., Compagno M., Smith P., Muramatsu M., Honjo T., Morse H.C., Nussenzweig M.C., Dalla-Favera R. AID is required for germinal center-derived lymphomagenesis. Nat. Genet. 2008, 40:108-112.
53. Kotani A., Kakazu N., Tsuruyama T., Okazaki I.M., Muramatsu M., Kinoshita K., Nagaoka H., Yabe D., Honjo T. Activation-induced cytidine deaminase (AID) promotes B cell lymphomagenesis in Emu-cmyc transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:1616-1620.
54. Hakim O., Resch W., Yamane A., Klein I., Kieffer-Kwon K.R., Jankovic M., Oliveira T., Bothmer A., Voss T.C., Ansarah-Sobrinho C., Mathe E., Liang G., Cobell J., Nakahashi H., Robbiani D.F., Nussenzweig A., Hager G.L., Nussenzweig M.C., Casellas R. DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes. Nature 2012, 484:69-74.
55. Klein I.A., Resch W., Jankovic M., Oliveira T., Yamane A., Nakahashi H., Di Virgilio M., Bothmer A., Nussenzweig A., Robbiani D.F., Casellas R., Nussenzweig M.C. Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell 2011, 147:95-106.
56. Burns M.B., Lackey L., Carpenter M.A., Rathore A., Land A.M., Leonard B., Refsland E.W., Kotandeniya D., Tretyakova N., Nikas J.B., Yee D., Temiz N.A., Donohue D.E., McDougle R.M., Brown W.L., Law E.K., Harris R.S. APOBEC3B is an enzymatic source of mutation in breast cancer. Nature 2013, 494:366-370.
57. Nilsen H., Haushalter K.A., Robins P., Barnes D.E., Verdine G.L., Lindahl T. Excision of deaminated cytosine from the vertebrate genome: role of the SMUG1 uracil-DNA glycosylase. EMBO J. 2001, 20:4278-4286.
58. An Q., Robins P., Lindahl T., Barnes D.E. C --> T mutagenesis and gamma-radiation sensitivity due to deficiency in the Smug1 and Ung DNA glycosylases. EMBO J. 2005, 24:2205-2213.
59. Hauser J., Sveshnikova N., Wallenius A., Baradaran S., Saarikettu J., Grundstrom T. B-cell receptor activation inhibits AID expression through calmodulin inhibition of E-proteins. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:1267-1272.
60. Wallenius A., Hauser J., Aas P.A., Sarno A., Kavli B., Krokan H.E., Grundstrom T. Expression and recruitment of uracil-DNA glycosylase are regulated by E2A during antibody diversification. Mol. Immunol. 2014, 60:23-31.
61. Phan R.T., Dalla-Favera R. The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells. Nature 2004, 432:635-639.
62. Kuppers R., Dalla-Favera R. Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene 2001, 20:5580-5594.
63. Dorsett Y., Robbiani D.F., Jankovic M., Reina-San-Martin B., Eisenreich T.R., Nussenzweig M.C. A role for AID in chromosome translocations between c-myc and the IgH variable region. J. Exp. Med. 2007, 204:2225-2232.
64. Leuenberger M., Frigerio S., Wild P.J., Noetzli F., Korol D., Zimmermann D.R., Gengler C., Probst-Hensch N.M., Moch H., Tinguely M. AID protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma is associated with poor prognosis and complex genetic alterations. Mod. Pathol. 2010, 23:177-186. (an official journal of the United States and Canadian Academy of Pathology, Inc).
65. Willenbrock K., Renne C., Rottenkolber M., Klapper W., Dreyling M., Engelhard M., Kuppers R., Hansmann M.L., Jungnickel B. The expression of activation induced cytidine deaminase in follicular lymphoma is independent of prognosis and stage. Histopathology 2009, 54:509-512.
66. Orthwein A., Di Noia J.M. Activation induced deaminase: how much and where?. Semin. Immunol. 2012, 24:246-254.
67. Andersen S., Ericsson M., Dai H.Y., Pena-Diaz J., Slupphaug G., Nilsen H., Aarset H., Krokan H.E. Monoclonal B-cell hyperplasia and leukocyte imbalance precede development of B-cell malignancies in uracil-DNA glycosylase deficient mice. DNA Repair 2005, 4:1432-1441.
68. Nilsen H., Stamp G., Andersen S., Hrivnak G., Krokan H.E., Lindahl T., Barnes D.E. Gene-targeted mice lacking the Ung uracil-DNA glycosylase develop B-cell lymphomas. Oncogene 2003, 22:5381-5386.
69. Gruber T.A., Chang M.S., Sposto R., Muschen M. Activation-induced cytidine deaminase accelerates clonal evolution in BCR-ABL1-driven B-cell lineage acute lymphoblastic leukemia. Cancer Res. 2010, 70:7411-7420.
70. Klemm L., Duy C., Iacobucci I., Kuchen S., von Levetzow G., Feldhahn N., Henke N., Li Z., Hoffmann T.K., Kim Y.M., Hofmann W.K., Jumaa H., Groffen J., Heisterkamp N., Martinelli G., Lieber M.R., Casellas R., Muschen M. The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemia. Cancer Cell 2009, 16:232-245.