Chromosomal aberrations in chronic lymphocytic leukaemia – prognostic and predictive role

Authors: L. Krůzová;  T. Papajík;  H. Urbánková
Authors‘ workplace: Hemato-onkologická klinika Lékařské fakulty Univerzity Palackého v Olomouci a Fakultní nemocnice Olomouc
Published in: Transfuze Hematol. dnes,1, 2020, No. Online only, p. 1-24.


Chromosomal aberrations play an important role in the pathogenesis and development of chronic lymphocytic leukaemia (CLL). They characterize the course of the disease and influence decisions regarding treatment. Aberrations with well-known prognostic significance include deletions of regions 11q, 13q, 17p and trisomy of chromosome 12. The importance of other recurrent cytogenetic abnormalities, such as duplications of 2p or 8q24, deletion of 6q21, translocations of 14q32 and complex karyotype have recently come under closer scrutiny. Chromosome aberrations are detected by classical G-banding, fluorescent in situ hybridization (FISH) and in some cases by contemporary array comparative genomic hybridization (arrayCGH). The implementation of next generation sequencing (NGS) has helped identify new gene mutations (particularly TP53, NOTCH1, SF3B1 and BIRC3), which refine patient stratification and influence the choice of treatment strategy. In future, prognostic and predictive models resulting from the combination of all mentioned methods will better reflect disease dynamics and clonal evolution and lead to a more accurate assessment of treatment response and survival.


chronic lymphocytic leukaemia – chromosomal aberrations – prognostic factors – cytogenetics – Fish


1. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127(20):2375–2390.

2. Juliusson G, Merup M. Cytogenetics in chronic lymphocytic leukemia. Semin Oncol 1998;25(1):19–26.

3. Juliusson G, Gahrton G. Chromosome aberrations in B-cell chronic lymphocytic leukemia. Pathogenetic and clinical implications. Cancer Genet Cytogenet 1990;45(2):143–160.

4. Juliusson G, Oscier DG, Fitchett M, et al. Prognostic subgroups in B-cell chronic lymphocytic leukemia defined by specific chromosomal abnormalities. N Engl J Med 1990;323(11):720–724.

5. Dicker F, Schnittger S, Haferlach T, Kern W, Schoch C. Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: A study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression. Blood 2006;108(9):3152–3160.

6. Decker T, Schneller F, Sparwasser T, et al. Immunostimulatory CpG-oligonucleotides cause proliferation, cytokine production, and an immunogenic phenotype in chronic lymphocytic leukemia B cells. Blood 2000;95(3):999–1006.

7. Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000;343(26):1910–1916.

8. Huh YO, Lin KI, Vega F, et al. MYC translocation in chronic lymphocytic leukaemia is associated with increased prolymphocytes and a poor prognosis. Br J Haematol 2008;142(1):36–44.

9. Li Y, Hu S, Wang SA, et al. The clinical significance of 8q24/MYC rearrangement in chronic lymphocytic leukemia. Mod Pathol 2016;29(5):444–451.

10. Haferlach C, Dicker F, Schnittger S, Kern W, Haferlach T. Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgV(H) status and immunophenotyping. Leukemia 2007;21(12):2442–2451.

11. Cavazzini F, Hernandez JA, Gozzetti A, et al. Chromosome 14q32 translocations involving the immunoglobulin heavy chain locus in chronic lymphocytic leukaemia identify a disease subset with poor prognosis. Br J Haematol 2008;142(4):529–537.

12. Jarosova M, Urbankova H, Plachy R, et al. Gain of chromosome 2p in chronic lymphocytic leukemia: significant heterogeneity and a new recurrent dicentric rearrangement. Leuk Lymphoma 2010;51(2):304–313.

13. Baliakas P, Jeromin S, Iskas M, et al. Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact. Blood 2019;133(11):1205–1216.

14. Kruzova L, Schneiderova P, Holzerova M, et al. Complex karyotype as a predictor of high-risk chronic lymphocytic leukemia: A single center experience over 12 years. Leuk Res 2019;85:106218.

15. Lane DP. Cancer. p53, guardian of the genome. Nature 1992;358(6381):15–16.

16. Mayr C, Speicher MR, Kofler DM, et al. Chromosomal translocations are associated with poor prognosis in chronic lymphocytic leukemia. Blood 2006;107(2):742–751.

17. Dohner H, Fischer K, Bentz M, et al. p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood 1995;85(6):1580–1589.

18. Brieghel C, Kinalis S, Yde CW, et al. Deep targeted sequencing of TP53 in chronic lymphocytic leukemia: clinical impact at diagnosis and at time of treatment. Haematologica 2019;104(4):789–796.

19. Zenz T, Krober 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 2008;112(8):3322–3329.

20. 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 2009;23(1):117–124.

21. Zainuddin N, Berglund M, Wanders A, et al. TP53 mutations predict for poor survival in de novo diffuse large B-cell lymphoma of germinal center subtype. Leuk Res 2009;33(1):60–66.

22. Delgado J, Espinet B, Oliveira AC, et al. Chronic lymphocytic leukaemia with 17p deletion: a retrospective analysis of prognostic factors and therapy results. Br J Haematol 2012;157(1):67–74.

23. Fabris S, Mosca L, Todoerti K, et al. Molecular and transcriptional characterization of 17p loss in B-cell chronic lymphocytic leukemia. Genes Chromosomes Cancer 2008;47(9):781–793.

24. Zenz T, Vollmer D, Trbusek M, et al. TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations. Leukemia 2010;24(12):2072–2079.

25. Landau DA, Carter SL, Stojanov P, et al. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell 2013;152(4):714–726.

26. Nadeu F, Delgado J, Royo C, et al. Clinical impact of clonal and subclonal TP53, SF3B1, BIRC3, NOTCH1 and ATM mutations in chronic lymphocytic leukemia. Blood 2016;127(17):2122–2130.

27. Nadeu F, Clot G, Delgado J, et al. Clinical impact of the subclonal architecture and mutational complexity in chronic lymphocytic leukemia. Leukemia 2018;32(3):645–653.

28. Van Dyke DL, Werner L, Rassenti LZ, et al. The Dohner fluorescence in situ hybridization prognostic classification of chronic lymphocytic leukaemia (CLL): the CLL Research Consortium experience. Br J Haematol 2016;173(1):105–113.

29. Yu L, Kim HT, Kasar S, et al. Survival of Del17p CLL Depends on genomic complexity and somatic mutation. Clin Cancer Res 2017;23(3):735–745.

30. Marasca R, Maffei R, Martinelli S, et al. Clinical heterogeneity of de novo 11q deletion chronic lymphocytic leukaemia: prognostic relevance of extent of 11q deleted nuclei inside leukemic clone. Hematol Oncol 2013;31(2):88–95.

31. Schaffner C, Stilgenbauer S, Rappold GA, Dohner H, Lichter P. Somatic ATM mutations indicate a pathogenic role of ATM in B-cell chronic lymphocytic leukemia. Blood 1999;94(2):748–753.

32. Rose-Zerilli MJ, Forster J, Parker H, et al. ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia: data from the UK LRF CLL4 trial. Haematologica 2014;99(4):736–742.

33. Rossi D, Fangazio M, Rasi S, et al. Disruption of BIRC3 associates with fludarabine chemorefractoriness in TP53 wild-type chronic lymphocytic leukemia. Blood 2012;119(12):2854–2862.

34. Jain P, Keating M, Thompson PA, et al. High fluorescence in situ hybridization percentage of deletion 11q in patients with chronic lymphocytic leukemia is an independent predictor of adverse outcome. Am J Hematol 2015;90(6):471–477.

35. Kipps TJ, Fraser G, Coutre SE, et al. Long-term studies assessing outcomes of ibrutinib therapy in patients with del(11q) chronic lymphocytic leukemia. Clin Lymphoma Myeloma Leuk 2019;19(11):715–722.e6.

36. Ouillette P, Erba H, Kujawski L, Kaminski M, Shedden K, Malek SN. Integrated genomic profiling of chronic lymphocytic leukemia identifies subtypes of deletion 13q14. Cancer Res 2008;68(4):1012–1021.

37. Ouillette P, Collins R, Shakhan S, et al. The prognostic significance of various 13q14 deletions in chronic lymphocytic leukemia. Clin Cancer Res 2011;17(21):6778–6790.

38. Puiggros A, Delgado J, Rodriguez-Vicente A, et al. Biallelic losses of 13q do not confer a poorer outcome in chronic lymphocytic leukaemia: analysis of 627 patients with isolated 13q deletion. Br J Haematol 2013;163(1):47–54.

39. Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 2002;99(24):15524–15529.

40. Calin GA, Ferracin M, Cimmino A, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 2005;353(17):1793–1801.

41. Klein U, Lia M, Crespo M, et al. The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell 2010;17(1):28–40.

42. Parker H, Rose-Zerilli MJ, Parker A, et al. 13q deletion anatomy and disease progression in patients with chronic lymphocytic leukemia. Leukemia 2011;25(3):489–497.

43. Lia M, Carette A, Tang H, et al. Functional dissection of the chromosome 13q14 tumor-suppressor locus using transgenic mouse lines. Blood 2012;119(13):2981–2990.

44. Grygalewicz B, Woroniecka R, Rygier J, et al. Monoallelic and biallelic deletions of 13q14 in a group of CLL/SLL patients investigated by CGH Haematological Cancer and SNP array (8x60K). Mol Cytogenet 2016;9:1.

45. Chena C, Avalos JS, Bezares RF, et al. Biallelic deletion 13q14.3 in patients with chronic lymphocytic leukemia: cytogenetic, FISH and clinical studies. Eur J Haematol 2008;81(2):94–99.

46. Humplikova L, Kollinerova S, Papajik T, et al. Expression of miR-15a and miR-16-1 in patients with chronic lymphocytic leukemia. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2013;157(4):284–293.

47. Garg R, Wierda W, Ferrajoli A, et al. The prognostic difference of monoallelic versus biallelic deletion of 13q in chronic lymphocytic leukemia. Cancer 2012;118(14):3531–3537.

48. Puiggros A, Venturas M, Salido M, et al. Interstitial 13q14 deletions detected in the karyotype and translocations with concomitant deletion at 13q14 in chronic lymphocytic leukemia: different genetic mechanisms but equivalent poorer clinical outcome. Genes Chromosomes Cancer 2014;53(9):788–797.

49. Dal Bo M, Rossi FM, Rossi D, et al. 13q14 deletion size and number of deleted cells both influence prognosis in chronic lymphocytic leukemia. Genes Chromosomes Cancer 2011;50(8):633–643.

50. Delgado J, Aventin A, Briones J, Sanchez J, Nomdedeu J, Sierra J. The use of tetradecanoylphorbol acetate-stimulated peripheral blood cells enhances the prognostic value of interphase fluorescence in situ hybridization in patients with chronic lymphocytic leukemia. Genes Chromosomes Cancer 2010;49(4):327–332.

51. Hernandez JA, Rodriguez AE, Gonzalez M, et al. A high number of losses in 13q14 chromosome band is associated with a worse outcome and biological differences in patients with B-cell chronic lymphoid leukemia. Haematologica 2009;94(3):364–371.

52. Van Dyke DL, Shanafelt TD, Call TG, et al. A comprehensive evaluation of the prognostic significance of 13q deletions in patients with B-chronic lymphocytic leukaemia. Br J Haematol 2010;148(4):544–550.

53. Ibbotson R, Athanasiadou A, Sutton LA, et al. Coexistence of trisomies of chromosomes 12 and 19 in chronic lymphocytic leukemia occurs exclusively in the rare IgG-positive variant. Leukemia 2012;26(1):170–172.

54. Porpaczy E, Bilban M, Heinze G, et al. Gene expression signature of chronic lymphocytic leukaemia with Trisomy 12. Eur J Clin Invest 2009;39(7):568–575.

55. 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 2012;97(3):437–441.

56. Zucchetto A, Caldana C, Benedetti D, et al. CD49d is overexpressed by trisomy 12 chronic lymphocytic leukemia cells: evidence for a methylation-dependent regulation mechanism. Blood 2013;122(19):3317–3321.

57. Athanasiadou A, Stamatopoulos K, Tsompanakou A, et al. Clinical, immunophenotypic, and molecular profiling of trisomy 12 in chronic lymphocytic leukemia and comparison with other karyotypic subgroups defined by cytogenetic analysis. Cancer Genet Cytogenet 2006;168(2):109–119.

58. Balatti V, Lerner S, Rizzotto L, et al. Trisomy 12 CLLs progress through NOTCH1 mutations. Leukemia 2013;27(3):740–743.

59. Strati P, Abruzzo LV, Wierda WG, O'Brien S, Ferrajoli A, Keating MJ. Second cancers and Richter transformation are the leading causes of death in patients with trisomy 12 chronic lymphocytic leukemia. Clin Lymphoma Myeloma Leuk 2015;15(7):420–427.

60. Chigrinova E, Rinaldi A, Kwee I, et al. Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome. Blood 2013;122(15):2673–2682.

61. Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nature Reviews Cancer 2008;8:976.

62. Krysov S, Dias S, Paterson A, et al. Surface IgM stimulation induces MEK1/2-dependent MYC expression in chronic lymphocytic leukemia cells. Blood 2012;119(1):170–179.

63. Rossi D, Spina V, Deambrogi C, et al. The genetics of Richter syndrome reveals disease heterogeneity and predicts survival after transformation. Blood 2011;117(12):3391–3401.

64. Put N, Van Roosbroeck K, Konings P, et al. Chronic lymphocytic leukemia and prolymphocytic leukemia with MYC translocations: a subgroup with an aggressive disease course. Ann Hematol 2012;91(6):863–873.

65. Blanco G, Puiggros A, Baliakas P, et al. Karyotypic complexity rather than chromosome 8 abnormalities aggravates the outcome of chronic lymphocytic leukemia patients with TP53 aberrations. Oncotarget 2016;7(49):80916–80924.

66. Chapiro E, Lesty C, Gabillaud C, et al. "Double-hit" chronic lymphocytic leukemia: An aggressive subgroup with 17p deletion and 8q24 gain. Am J Hematol 2018;93(3):375–382.

67. Stilgenbauer S, Bullinger L, Benner A, et al. Incidence and clinical significance of 6q deletions in B cell chronic lymphocytic leukemia. Leukemia 1999;13(9):1331–1334.

68. Jarosova M, Hruba M, Oltova A, et al. Chromosome 6q deletion correlates with poor prognosis and low relative expression of FOXO3 in chronic lymphocytic leukemia patients. Am J Hematol 2017;92(10):E604–E607.

69. Finn WG, Kay NE, Kroft SH, Church S, Peterson LC. Secondary abnormalities of chromosome 6q in B-cell chronic lymphocytic leukemia: a sequential study of karyotypic instability in 51 patients. Am J Hematol 1998;59(3):223–229.

70. Cuneo A, Rigolin GM, Bigoni R, et al. Chronic lymphocytic leukemia with 6q- shows distinct hematological features and intermediate prognosis. Leukemia 2004;18(3):476–483.

71. Urbankova H, Papajik T, Plachy R, et al. Array-based karyotyping in chronic lymphocytic leukemia (CLL) detects new unbalanced abnormalities that escape conventional cytogenetics and CLL FISH panel. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014;158(1):56–64.

72. Ticchioni M, Essafi M, Jeandel PY, et al. Homeostatic chemokines increase survival of B-chronic lymphocytic leukemia cells through inactivation of transcription factor FOXO3a. Oncogene 2007;26(50):7081–7091.

73. Van Den Neste E, Robin V, Francart J, et al. Chromosomal translocations independently predict treatment failure, treatment-free survival and overall survival in B-cell chronic lymphocytic leukemia patients treated with cladribine. Leukemia 2007;21(8):1715–1722.

74. Cavazzini F, Rizzotto L, Sofritti O, et al. Clonal evolution including 14q32/IGH translocations in chronic lymphocytic leukemia: analysis of clinicobiologic correlations in 105 patients. Leuk Lymphoma 2012;53(1):83–88.

75. Berkova A, Pavlistova L, Babicka L, et al. Combined molecular biological and molecular cytogenetic analysis of genomic changes in 146 patients with B-cell chronic lymphocytic leukemia. Neoplasma 2008;55(5):400–408.

76. Kojima K, Taniwaki M, Yoshino T, et al. Trisomy 12 and t(14;18) in B-cell chronic lymphocytic leukemia. Int J Hematol 1998;67(2):199–203.

77. Sen F, Lai R, Albitar M. Chronic lymphocytic leukemia with t(14;18) and trisomy 12. Arch Pathol Lab Med 2002;126(12):1543-6.

78. Michaux L, Mecucci C, Stul M, et al. BCL3 rearrangement and t(14;19)(q32;q13) in lymphoproliferative disorders. Genes Chromosomes Cancer 1996;15(1):38–47.

79. Ohno H, Doi S, Yabumoto K, Fukuhara S, McKeithan TW. Molecular characterization of the t(14;19)(q32;q13) translocation in chronic lymphocytic leukemia. Leukemia 1993;7(12):2057–2063.

80. Huh YO, Abruzzo LV, Rassidakis GZ, et al. The t(14;19)(q32;q13)-positive small B-cell leukaemia: a clinicopathologic and cytogenetic study of seven cases. Br J Haematol 2007;136(2):220–228.

81. Lu G, Kong Y, Yue C. Genetic and immunophenotypic profile of IGH@ rearrangement detected by fluorescence in situ hybridization in 149 cases of B-cell chronic lymphocytic leukemia. Cancer Genet Cytogenet 2010;196(1):56–63.

82. Martin-Subero JI, Ibbotson R, Klapper W, et al. A comprehensive genetic and histopathologic analysis identifies two subgroups of B-cell malignancies carrying a t(14;19)(q32;q13) or variant BCL3-translocation. Leukemia 2007;21(7):1532–1544.

83. Huh YO, Schweighofer CD, Ketterling RP, et al. Chronic lymphocytic leukemia with t(14;19)(q32;q13) is characterized by atypical morphologic and immunophenotypic features and distinctive genetic features. Am J Clin Pathol 2011;135(5):686–696.

84. Nguyen-Khac F, Chapiro E, Lesty C, et al. Specific chromosomal IG translocations have different prognoses in chronic lymphocytic leukemia. Am J Blood Res 2011;1(1):13–21.

85. Fang H, Reichard KK, Rabe KG, et al. IGH translocations in chronic lymphocytic leukemia: Clinicopathologic features and clinical outcomes. Am J Hematol 2019;94(3):338–345.

86. Yin CC, Lin KI, Ketterling RP, et al. Chronic lymphocytic leukemia With t(2;14)(p16;q32) involves the BCL11A and IgH genes and is associated with atypical morphologic features and unmutated IgVH genes. Am J Clin Pathol 2009;131(5):663–670.

87. Satterwhite E, Sonoki T, Willis TG, et al. The BCL11 gene family: involvement of BCL11A in lymphoid malignancies. Blood 2001;98(12):3413–3420.

88. Brizard F, Dreyfus B, Guilhot F, Tanzer J, Brizard A. 11q13 rearrangement in B cell chronic lymphocytic leukemia. Leuk Lymphoma 1997;25(5-6):539–543.

89. Avet-Loiseau H, Garand R, Gaillard F, et al. Detection of t(11;14) using interphase molecular cytogenetics in mantle cell lymphoma and atypical chronic lymphocytic leukemia. Genes Chromosomes Cancer 1998;23(2):175–182.

90. Wlodarska I, Matthews C, Veyt E, et al. Telomeric IGH losses detectable by fluorescence in situ hybridization in chronic lymphocytic leukemia reflect somatic VH recombination events. J Mol Diagn 2007;9(1):47–54.

91. Quintero-Rivera F, Nooraie F, Rao PN. Frequency of 5'IGH deletions in B-cell chronic lymphocytic leukemia. Cancer Genet Cytogenet 2009;190(1):33-9.

92. Haferlach C, Jeronim S, Stengel A, et al. In chronic lymphocytic leukemia the gain of the short arm of chromosome 2 is highly associated with an unmutated IGHV status, 11q/ATM deletion, SF3B1 mutation and a complex karyotype. The American Society of Hematology; 2016; 128(22):4379.

93. Houldsworth J, Olshen AB, Cattoretti G, et al. Relationship between REL amplification, REL function, and clinical and biologic features in diffuse large B-cell lymphomas. Blood 2004;103(5):1862–1868.

94. Scandurra M, Rossi D, Deambrogi C, et al. Genomic profiling of Richter's syndrome: recurrent lesions and differences with de novo diffuse large B-cell lymphomas. Hematol Oncol 2010;28(2):62–67.

95. Chapiro E, Leporrier N, Radford-Weiss I, et al. Gain of the short arm of chromosome 2 (2p) is a frequent recurring chromosome aberration in untreated chronic lymphocytic leukemia (CLL) at advanced stages. Leuk Res 2010;34(1):63–68.

96. Ma D, Chen Z, Patel KP, et al. Array comparative genomic hybridization analysis identifies recurrent gain of chromosome 2p25.3 involving the ACP1 and MYCN genes in chronic lymphocytic leukemia. Clin Lymphoma Myeloma Leuk 2011;11 Suppl 1:S17–S24.

97. Fabris S, Mosca L, Cutrona G, et al. Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia. Am J Hematol 2013;88(1):24–31.

98. Brejcha M, Stoklasova M, Brychtova Y, et al. Clonal evolution in chronic lymphocytic leukemia detected by fluorescence in situ hybridization and conventional cytogenetics after stimulation with CpG oligonucleotides and interleukin-2: a prospective analysis. Leuk Res 2014;38(2):170–175.

99. Ouillette P, Saiya-Cork K, Seymour E, Li C, Shedden K, Malek SN. Clonal evolution, genomic drivers, and effects of therapy in chronic lymphocytic leukemia. Clin Cancer Res 2013;19(11):2893–2904.

100. Nowell PC, Moreau L, Growney P, Besa EC. Karyotypic stability in chronic B-cell leukemia. Cancer Genet Cytogenet 1988;33(2):155–160.

101. Fegan C, Robinson H, Thompson P, Whittaker JA, White D. Karyotypic evolution in CLL: identification of a new sub-group of patients with deletions of 11q and advanced or progressive disease. Leukemia 1995;9(12):2003–2008.

102. Koski T, Karhu R, Visakorpi T, Vilpo L, Knuutila S, Vilpo J. Complex chromosomal aberrations in chronic lymphocytic leukemia are associated with cellular drug and irradiation resistance. Eur J Haematol 2000;65(1):32–39.

103. Wierda W, O'Brien S, Wen S, et al. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol 2005;23(18):4070–4078.

104. Loscertales J, Arranz E, Sanz MA, et al. Clonal evolution in patients with chronic lymphocytic leukemia. Leuk Lymphoma 2010;51(6):1142–1143.

105. Brugat T, Nguyen-Khac F, Grelier A, Merle-Beral H, Delic J. Telomere dysfunction-induced foci arise with the onset of telomeric deletions and complex chromosomal aberrations in resistant chronic lymphocytic leukemia cells. Blood 2010;116(2):239–249.

106. Puiggros A, Collado R, Calasanz MJ, et al. Patients with chronic lymphocytic leukemia and complex karyotype show an adverse outcome even in absence of TP53/ATM FISH deletions. Oncotarget 2017;8(33):54297–54303.

107. Thompson PA, O'Brien SM, Wierda WG, et al. Complex karyotype is a stronger predictor than del(17p) for an inferior outcome in relapsed or refractory chronic lymphocytic leukemia patients treated with ibrutinib-based regimens. Cancer 2015;121(20):3612–3621.

108. Doubek M, Špaček M, Pospíšilová Š, et al. Doporučení pro diagnostiku a léčbu chronické lymfocytární leukemie (CLL) – 2018 Transfuze Hematol dnes 2018;24(3):208–220.

109. Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood 2018;131(25):2745–2760.

110. Parikh SA, Strati P, Tsang M, West CP, Shanafelt TD. Should IGHV status and FISH testing be performed in all CLL patients at diagnosis? A systematic review and meta-analysis. Blood 2016;127(14):1752–1760.

Haematology Internal medicine Clinical oncology
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