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Review

Molecular genetics of high-risk chronic lymphocytic leukemia

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Pages 593-602 | Published online: 10 Jan 2014

References

  • Stilgenbauer S, Zenz T. Understanding and managing ultra high-risk chronic lymphocytic leukemia. Hematology Am. Soc. Hematol. Educ. Program 2010, 481–488 (2010).
  • Zenz T, Gribben JG, Hallek M, Döhner H, Keating MJ, Stilgenbauer S. Risk categories and refractory CLL in the era of chemoimmunotherapy. Blood 119(18), 4101–4107 (2012).
  • Dreger P, Corradini P, Kimby E et al.; Chronic Leukemia Working Party of the EBMT. Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus. Leukemia 21(1), 12–17 (2007).
  • Hallek M, Fischer K, Fingerle-Rowson G et al.; International Group of Investigators; German Chronic Lymphocytic Leukaemia Study Group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, Phase 3 trial. Lancet 376(9747), 1164–1174 (2010).
  • Zenz T, Eichhorst B, Busch R et al. TP53 mutation and survival in chronic lymphocytic leukemia. J. Clin. Oncol. 28(29), 4473–4479 (2010).
  • Catovsky D, Richards S, Matutes E et al. UK National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group; NCRI Chronic Lymphocytic Leukaemia Working Group. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet 370(9583), 230–239 (2007).
  • Gonzalez D, Martinez P, Wade R et al. Mutational status of the TP53 gene as a predictor of response and survival in patients with chronic lymphocytic leukemia: results from the LRF CLL4 Trial. J. Clin. Oncol. 29(16), 2223–2229 (2011).
  • Stilgenbauer S, Zenz T, Winkler D et al. German Chronic Lymphocytic Leukemia Study Group. Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J. Clin. Oncol. 27(24), 3994–4001 (2009).
  • Zenz T, Häbe S, Denzel T et al. Detailed analysis of p53 pathway defects in fludarabine-refractory chronic lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trial. Blood 114(13), 2589–2597 (2009).
  • Fabbri G, Rasi S, Rossi D et al. Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation. J. Exp. Med. 208(7), 1389–1401 (2011).
  • Puente XS, Pinyol M, Quesada V et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 475(7354), 101–105 (2011).
  • Quesada V, Conde L, Villamor N et al. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat. Genet. 44(1), 47–52 (2012).
  • Rossi D, Bruscaggin A, Spina V et al. Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. Blood 118(26), 6904–6908 (2011).
  • Wang L, Lawrence MS, Wan Y et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N. Engl. J. Med. 365(26), 2497–2506 (2011).
  • Sportoletti P, Baldoni S, Cavalli L et al. NOTCH1 PEST domain mutation is an adverse prognostic factor in B-CLL. Br. J. Haematol. 151(4), 404–406 (2010).
  • Rossi D, Rasi S, Fabbri G et al. Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. Blood 119(2), 521–529 (2012).
  • Rossi D, Fangazio M, Rasi S et al. Disruption of BIRC3 associates with fludarabine chemorefractoriness in TP53 wild-type chronic lymphocytic leukemia. Blood 119(12), 2854–2862 (2012).
  • Brown CJ, Lain S, Verma CS, Fersht AR, Lane DP. Awakening guardian angels: drugging the p53 pathway. Nat. Rev. Cancer 9(12), 862–873 (2009).
  • Döhner H, Stilgenbauer S, Benner A et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N. Engl. J. Med. 343(26), 1910–1916 (2000).
  • Zenz T, Kröber A, Scherer K et al. Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up. Blood 112(8), 3322–3329 (2008).
  • Dicker F, Herholz H, Schnittger S et al. The detection of TP53 mutations in chronic lymphocytic leukemia independently predicts rapid disease progression and is highly correlated with a complex aberrant karyotype. Leukemia 23(1), 117–124 (2009).
  • Malcikova J, Smardova J, Rocnova L et al. Monoallelic and biallelic inactivation of TP53 gene in chronic lymphocytic leukemia: selection, impact on survival, and response to DNA damage. Blood 114(26), 5307–5314 (2009).
  • Rossi D, Cerri M, Deambrogi C et al. The prognostic value of TP53 mutations in chronic lymphocytic leukemia is independent of Del17p13: implications for overall survival and chemorefractoriness. Clin. Cancer Res. 15(3), 995–1004 (2009).
  • Rossi D, Spina V, Deambrogi C et al. The genetics of Richter syndrome reveals disease heterogeneity and predicts survival after transformation. Blood 117(12), 3391–3401 (2011).
  • Zainuddin N, Murray F, Kanduri M et al. TP53 mutations are infrequent in newly diagnosed chronic lymphocytic leukemia. Leuk. Res. 35(2), 272–274 (2011).
  • Zenz T, Vollmer D, Trbusek M et al. European Research Initiative on CLL (ERIC). TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations. Leukemia 24(12), 2072–2079 (2010).
  • Tam CS, Shanafelt TD, Wierda WG et al. De novo deletion 17p13.1 chronic lymphocytic leukemia shows significant clinical heterogeneity: the M. D. Anderson and Mayo Clinic experience. Blood 114(5), 957–964 (2009).
  • Eichhorst BF, Busch R, Hopfinger G et al. German CLL Study Group. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood 107(3), 885–891 (2006).
  • Bosch F, Abrisqueta P, Villamor N et al. Rituximab, fludarabine, cyclophosphamide, and mitoxantrone: a new, highly active chemoimmunotherapy regimen for chronic lymphocytic leukemia. J. Clin. Oncol. 27(27), 4578–4584 (2009).
  • Schlette EJ, Admirand J, Wierda W et al. p53 expression by immunohistochemistry is an important determinant of survival in patients with chronic lymphocytic leukemia receiving frontline chemo-immunotherapy. Leuk. Lymphoma 50(10), 1597–1605 (2009).
  • Trbusek M, Smardova J, Malcikova J et al. Missense mutations located in structural p53 DNA-binding motifs are associated with extremely poor survival in chronic lymphocytic leukemia. J. Clin. Oncol. 29(19), 2703–2708 (2011).
  • Marinelli M, Raponi S, Del Giudice I et al. Is the aberrant expression of p53 by immunocytochemistry a surrogate marker of TP53 mutation and/or deletion in chronic lymphocytic leukemia? Am. J. Clin. Pathol. 135(1), 173–174 (2011).
  • Hallek M, Cheson BD, Catovsky D et al.; International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute – Working Group 1996 guidelines. Blood 111(12), 5446–5456 (2008).
  • Pospisilova S, Gonzalez D, Malcikova J et al. European Research Initiative on CLL (ERIC). ERIC recommendations on TP53 mutation analysis in chronic lymphocytic leukemia. Leukemia 26(7), 1458–1461 (2012).
  • Dreger P, Döhner H, Ritgen M et al. German CLL Study Group. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood 116(14), 2438–2447 (2010).
  • Pettitt AR, Jackson R, Carruthers S et al. Alemtuzumab in combination with methylprednisolone is a highly effective induction regimen for patients with chronic lymphocytic leukemia and deletion of TP53: final results of the National Cancer Research Institute CLL206 trial. J. Clin. Oncol. 30(14), 1647–1655 (2012).
  • Lobry C, Oh P, Aifantis I. Oncogenic and tumor suppressor functions of Notch in cancer: it’s NOTCH what you think. J. Exp. Med. 208(10), 1931–1935 (2011).
  • Yuan JS, Kousis PC, Suliman S, Visan I, Guidos CJ. Functions of notch signaling in the immune system: consensus and controversies. Annu. Rev. Immunol. 28, 343–365 (2010).
  • Rothenberg EV. T cell lineage commitment: identity and renunciation. J. Immunol. 186(12), 6649–6655 (2011).
  • Santos MA, Sarmento LM, Rebelo M et al. Notch1 engagement by Delta-like-1 promotes differentiation of B lymphocytes to antibody-secreting cells. Proc. Natl Acad. Sci. USA 104(39), 15454–15459 (2007).
  • Aster JC, Blacklow SC, Pear WS. Notch signalling in T-cell lymphoblastic leukaemia/lymphoma and other haematological malignancies. J. Pathol. 223(2), 262–273 (2011).
  • Paganin M, Ferrando A. Molecular pathogenesis and targeted therapies for NOTCH1-induced T-cell acute lymphoblastic leukemia. Blood Rev. 25(2), 83–90 (2011).
  • Balatti V, Bottoni A, Palamarchuk A et al. NOTCH1 mutations in CLL associated with trisomy 12. Blood 119(2), 329–331 (2012).
  • Del Giudice I, Rossi D, Chiaretti S et al. NOTCH1 mutations in +12 chronic lymphocytic leukemia (CLL) confer an unfavorable prognosis, induce a distinctive transcriptional profiling and refine the intermediate prognosis of +12 CLL. Haematologica 97(3), 437–441 (2012).
  • López C, Delgado J, Costa D et al. Different distribution of NOTCH1 mutations in chronic lymphocytic leukemia with isolated trisomy 12 or associated with other chromosomal alterations. Genes Chromosomes Cancer 51(9), 881–889 (2012).
  • Rosati E, Sabatini R, Rampino G et al. Constitutively activated Notch signaling is involved in survival and apoptosis resistance of B-CLL cells. Blood 113(4), 856–865 (2009).
  • Rasi S, Monti S, Spina V, Foà R, Gaidano G, Rossi D. Analysis of NOTCH1 mutations in monoclonal B-cell lymphocytosis. Haematologica 97(1), 153–154 (2012).
  • Rossi D, Rasi S, Spina V et al. Different impact of NOTCH1 and SF3B1 mutations on the risk of chronic lymphocytic leukemia transformation to Richter syndrome. Br. J. Haematol. 158(3), 426–429 (2012).
  • Groth C, Fortini ME. Therapeutic approaches to modulating Notch signaling: current challenges and future prospects. Semin. Cell Dev. Biol. 23(4), 465–472 (2012).
  • Will CL, Lührmann R. Spliceosome structure and function. Cold Spring Harb. Perspect. Biol. 3(7), a003707 (2011).
  • David CJ, Manley JL. Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged. Genes Dev. 24(21), 2343–2364 (2010).
  • Luke MM, Della Seta F, Di Como CJ, Sugimoto H, Kobayashi R, Arndt KT. The SAP, a new family of proteins, associate and function positively with the SIT4 phosphatase. Mol. Cell. Biol. 16(6), 2744–2755 (1996).
  • Wang C, Chua K, Seghezzi W, Lees E, Gozani O, Reed R. Phosphorylation of spliceosomal protein SAP 155 coupled with splicing catalysis. Genes Dev. 12(10), 1409–1414 (1998).
  • Das BK, Xia L, Palandjian L, Gozani O, Chyung Y, Reed R. Characterization of a protein complex containing spliceosomal proteins SAPs 49, 130, 145, and 155. Mol. Cell. Biol. 19(10), 6796–6802 (1999).
  • Wahl MC, Will CL, Lührmann R. The spliceosome: design principles of a dynamic RNP machine. Cell 136(4), 701–718 (2009).
  • Papaemmanuil E, Cazzola M, Boultwood J et al. Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N. Engl. J. Med. 365(15), 1384–1395 (2011).
  • Yoshida K, Sanada M, Shiraishi Y et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 478(7367), 64–69 (2011).
  • Greco M, Capello D, Bruscaggin A et al. Analysis of SF3B1 mutations in monoclonal B-cell lymphocytosis. Hematol. Oncol. doi:10.1002/hon.2013 (2012) (Epub ahead of print).
  • Spitali P, Aartsma-Rus A. Splice modulating therapies for human disease. Cell 148(6), 1085–1088 (2012).
  • Kern C, Cornuel JF, Billard C et al. Involvement of BAFF and APRIL in the resistance to apoptosis of B-CLL through an autocrine pathway. Blood 103(2), 679–688 (2004).
  • Endo T, Nishio M, Enzler T et al. BAFF and APRIL support chronic lymphocytic leukemia B-cell survival through activation of the canonical NF-κB pathway. Blood 109(2), 703–710 (2007).
  • Hewamana S, Alghazal S, Lin TT et al. The NF-κB subunit Rel A is associated with in vitro survival and clinical disease progression in chronic lymphocytic leukemia and represents a promising therapeutic target. Blood 111(9), 4681–4689 (2008).
  • Buggins AG, Pepper C, Patten PE et al. Interaction with vascular endothelium enhances survival in primary chronic lymphocytic leukemia cells via NF-κB activation and de novo gene transcription. Cancer Res. 70(19), 7523–7533 (2010).
  • Herishanu Y, Pérez-Galán P, Liu D et al. The lymph node microenvironment promotes B-cell receptor signaling, NF-κB activation, and tumor proliferation in chronic lymphocytic leukemia. Blood 117(2), 563–574 (2011).
  • Vallabhapurapu S, Karin M. Regulation and function of NF-κB transcription factors in the immune system. Annu. Rev. Immunol. 27, 693–733 (2009).
  • Li X, Yang Y, Ashwell JD. TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2. Nature 416(6878), 345–347 (2002).
  • Zarnegar BJ, Wang Y, Mahoney DJ et al. Noncanonical NF-κB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK. Nat. Immunol. 9(12), 1371–1378 (2008).
  • Conze DB, Zhao Y, Ashwell JD. Non-canonical NF-κB activation and abnormal B cell accumulation in mice expressing ubiquitin protein ligase-inactive c-IAP2. PLoS Biol. 8(10), e1000518 (2010).
  • Rossi D, Deaglio S, Dominguez-Sola D et al. Alteration of BIRC3 and multiple other NF-κB pathway genes in splenic marginal zone lymphoma. Blood 118(18), 4930–4934 (2011).
  • Stilgenbauer S, Liebisch P, James MR et al. Molecular cytogenetic delineation of a novel critical genomic region in chromosome bands 11q22.3-923.1 in lymphoproliferative disorders. Proc. Natl Acad. Sci. USA 93(21), 11837–11841 (1996).
  • Schaffner C, Stilgenbauer S, Rappold GA, Döhner H, Lichter P. Somatic ATM mutations indicate a pathogenic role of ATM in B-cell chronic lymphocytic leukemia. Blood 94(2), 748–753 (1999).
  • Austen B, Powell JE, Alvi A et al. Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL. Blood 106(9), 3175–3182 (2005).
  • Guarini A, Marinelli M, Tavolaro S et al. ATM gene alterations in chronic lymphocytic leukemia patients induce a distinct gene expression profile and predict disease progression. Haematologica 97(1), 47–55 (2012).
  • Skowronska A, Austen B, Powell JE et al. ATM germline heterozygosity does not play a role in chronic lymphocytic leukemia initiation but influences rapid disease progression through loss of the remaining ATM allele. Haematologica 97(1), 142–146 (2012).
  • Hewamana S, Lin TT, Jenkins C et al. The novel nuclear factor-κB inhibitor LC-1 is equipotent in poor prognostic subsets of chronic lymphocytic leukemia and shows strong synergy with fludarabine. Clin. Cancer Res. 14(24), 8102–8111 (2008).
  • Hertlein E, Wagner AJ, Jones J et al. 17-DMAG targets the nuclear factor-κB family of proteins to induce apoptosis in chronic lymphocytic leukemia: clinical implications of HSP90 inhibition. Blood 116(1), 45–53 (2010).
  • Woyach JA, Johnson AJ, Byrd JC. The B-cell receptor signaling pathway as a therapeutic target in CLL. Blood 120(6), 1175–1184 (2012).
  • Cheson BD, Byrd JC, Rai KR et al. Novel targeted agents and the need to refine clinical end points in chronic lymphocytic leukemia. J. Clin. Oncol. 30(23), 2820–2822 (2012).

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