CLL Tables: Regions of Recurrent Copy Number Change and CN-LOH

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Table 1 - Regions of Recurrent Copy Number Change in CLL (Literature Review). The is a list of clinically significant and/or recurrent CNAs selected and evaluated based on a systematic literature search performed on 72 peer-reviewed manuscripts focusing on CNAs and CN-LOH assessment in CLL published between 2000 and 2017. Table derived from Chun et al., 2018 [PMID 30554732] with permission from Cancer Genetics.

Chromosome/

Region

Abnormality Type Prevalence (%) Relevant Genes Strength of Evidence for Gene Prognostic Significance Strength of Evidence for Prognosis (Level*) Comments References
1p Gain ?2-5 Unknown N/A Favorable Suspected (2) [1] [2] [3]
1q23.2q23.3 Loss 15 Unknown N/A Unknown N/A (3) [4] [5] [6]
2p12p25.3 Gain 5-30 ACP1, MYCN, ALK, REL, BCL11A MYCN (Established), REL, BCL11A (Candidate) Unfavorable Established (if MYCN included) (1) [1] [2] [3] [4] [5] [7] [8] [9] [10] [11] [12] [13]
3p21.31 Loss 1-5 ATRIP, CDC25A Candidate Unknown N/A (3) [4] [14] [15]
3q Gain 2-19 Unknown N/A Unfavorable Suspected (2) Appears to be particularly prevalent in Japanese [2] [16] [17]
4p15.2p16.3 Loss 14 Unknown N/A Unfavorable (occurred with del(11q) or del(17p)) Suspected (2) [18]
6p25.3 Gain 1 Unknown N/A Unknown N/A (3) [4]
6p22.1 Loss 1 Histone cluster, HFE Candidate Unknown N/A (3) [4]
6q Loss 3-6 FOXO3 Candidate Intermediate Suspected (2) [19] [20] [21] [22]
7p Gain 5-6 Unknown N/A Intermediate Suspected (2) [2]
7q Loss 1-2 Unknown N/A Unknown N/A (3) [2] [10]
8p21 Loss 2-5 TRIM35 Candidate Unfavorable Suspected (2) Associated with established unfavorable changes (11q- and 17p-). Not established as an independent prognosticator [2] [23]
8q24.1 Gain 5 MYC Candidate Unfavorable Suspected (2) Often associated with 11q and 17p deletion; may not be independent [2] [2] [4]
9q13q21.11 Loss 1 Unknown N/A Unknown N/A (3) [4]
10q24 Loss 2 Unknown N/A Unknown N/A (3) Clustered around NFKB2 gene locus [4] [9] [24]
11q22.3 Loss 10-20 ATM, BIRC3, MRE11, H2AFX ATM established, Others Candidate Unfavorable Established (1) [25]
12 Gain 10-20 Unknown N/A Intermediate Established (1) Unfavorable if NOTCH1 mutation is present [25]
13q14 Loss 50-60 DLEU2, MIR15A, MIR16-1, DLEU1 Established Favorable Established (1) Co-deletion of RB1 may negatively impact time to treatment [25] [26] [27]
14q24.1q32.3 Loss 2 Unknown N/A Unknown N/A (3) Associated with trisomy 12 [4] [28] [29]
15q15.1 Loss 4 MGA Candidate Unknown N/A (3) [4] [9]
17p13.1 Loss 5-15 TP53 Established Unfavorable Established (1) [25]
17q Gain 1 Unknown N/A Unfavorable Suspected (2) [2]
18p Loss 3 Unknown N/A Unfavorable Suspected (2) [2] [4]
18 Gain 4 Unknown N/A Unfavorable Established (1) Associated with trisomy 12 [30]
19 Gain 2-5 Unknown N/A Unfavorable Established (1) Associated with trisomy 12 [4] [9] [18] [24] [30]
Genomic complexity 3 or more CNAs 10-15 N/A Unfavorable Established (1) [9] [10] [14] [31]
Chromothripsis (>10 copy number states of 2 and 3) 5 SETD2, other markers across genome not defined Established Unfavorable Established (1) [4] [27] [32]

*Level 1: present in WHO classification or professional practice guidelines; Level 2: recurrent in well-powered studies with suspected clinical significance; Level 3: recurrent, but uncertain prognostic significance.

Abbreviations: CNA = copy number aberration; CLL = chronic lymphocytic leukemia; CN-LOH = copy-neutral loss-of-heterozygosity


Table 2 - Recurring regions of CN-LOH in CLL. Table derived from Chun et al., 2018 [PMID 30554732] with permission from Cancer Genetics.

CN-LOH Candidate Gene Association Strength of Evidence for Prognosis (Level*) References
13q miR15a/16-1 Biallelic deletion of 13q Established (1) [33] [34] [35] [36] [37] [38] [39] [40]
17p13 TP53 Homozygous TP53 mutations Established (1) [33] [35] [41] [38] [42]
11q13-qter Includes ATM Monoallelic ATM deletion Suspected (2) [35] [38]
20q11 Unknown None N/A (3) [41] [43]
1p36 Unknown None N/A (3) [35] [44]

*Level 1: present in WHO classification or professional practice guidelines; Level 2: recurrent in well-powered studies with suspected clinical significance; Level 3: recurrent, but uncertain prognostic significance


Table 3 - Recurrent mutated genes in CLL. Table derived from Chun et al., 2018 [PMID 30554732] with permission from Cancer Genetics.

Gene Locus Function Mutation Type Prevalence (%) Prognostic Significance Strength of Evidence (Level*) Comments References
ATM 11q22.3 DNA repair and cell-cycle control Missense, nonsense, indel 10-14 Unfavorable Established (1) Associated with unmutIGHV and 11q-; Candidate driver gene [45] [46]
BIRC3 11q22.2 Apoptosis inhibitor Frameshift, nonsense, whole gene deletion 1-10

(higher in previously treated patients)

Unfavorable Established (1) In ~25% of fludarabine-refractory CLL; Candidate driver gene [47] [48] [49] [50]
CHD2 15q26.1 Chromatin remodeler Missense, truncation 5-10 Unknown N/A (3) [47] [51]
FBXW7 4q31.3 Ubiquitin ligase subunit/targets include NOTCH1 Missense 4 Unknown N/A (3) Exclusive to NOTCH1 mutation patients; Negatively regulates NOTCH1 [52]
MYD88 3p22.2 Inflammatory pathway signal transducer Missense 2-10 Favorable/

No effect

Suspected (2) Candidate driver gene [49] [50] [53]
NOTCH1 9q34.3 Intercellular signaling Missense, nonsense, insertion, duplication, frameshift 4-10

(diagnosis)

12-30

(progression)

Unfavorable Established (1) Associated with +12; Candidate driver gene [54] [46] [50] [55] [56]
POT1 7q31.33 Telomere protector/

stabilizer; component of telomerase RNP complex

Missense, frameshift, splicing 5-10 Unfavorable Suspected (2) Associated with familial CLL [57] [58] [59]
SF3B1 2q33.1 Spliceosome component Missense 10 -18 Unfavorable Established (1) Enriched in patients with del(11q) and unmutIGHV; Candidate driver gene for disease progression [49] [50] [60] [61] [62]
TP53 17p13.1 DNA repair and cell-cycle control Missense 5-10

(higher with progressive disease)

Unfavorable Established (1) [45] [47] [63] [64] [65]
XPO1 2p15 Exports proteins/RNA fragments from nucleus into cytoplasm Missense 5-7.5 Unfavorable/

high risk of progression

Suspected (2) Associated with unmutIGHV [66] [53] [67]

*Level 1: present in WHO classification or professional practice guidelines; Level 2: recurrent in well-powered studies with suspected clinical significance; Level 3: recurrent, but uncertain prognostic significance

Reference

  1. 1.0 1.1 D, Pfeifer; et al. (2007). "Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP arrays". PMID 17053054.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 J, Houldsworth; et al. (2014). "Genomic imbalance defines three prognostic groups for risk stratification of patients with chronic lymphocytic leukemia". doi:10.3109/10428194.2013.845882. PMC 6905429. PMID 24047479.CS1 maint: PMC format (link)
  3. 3.0 3.1 E, Chapiro; et al. (2010). "Gain of the short arm of chromosome 2 (2p) is a frequent recurring chromosome aberration in untreated chronic lymphocytic leukemia (CLL) at advanced stages". PMID 19406473.
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 J, Edelmann; et al. (2012). "High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations". PMID 23047824.
  5. 5.0 5.1 D, Ma; et al. (2011). "Array comparative genomic hybridization analysis identifies recurrent gain of chromosome 2p25.3 involving the ACP1 and MYCN genes in chronic lymphocytic leukemia". doi:10.1016/j.clml.2011.03.031. PMC 4845643. PMID 22035742.CS1 maint: PMC format (link)
  6. A, Tyybakinoja; et al. (2007). "High-resolution oligonucleotide array-CGH pinpoints genes involved in cryptic losses in chronic lymphocytic leukemia". PMID 17901694.
  7. L, Shao; et al. (2010). "Array comparative genomic hybridization detects chromosomal abnormalities in hematological cancers that are not detected by conventional cytogenetics". doi:10.2353/jmoldx.2010.090192. PMC 2928432. PMID 20724749.CS1 maint: PMC format (link)
  8. A, Patel; et al. (2008). "Validation of a targeted DNA microarray for the clinical evaluation of recurrent abnormalities in chronic lymphocytic leukemia". PMID 18161787.
  9. 9.0 9.1 9.2 9.3 9.4 Mj, Stevens-Kroef; et al. (2014). "Identification of prognostic relevant chromosomal abnormalities in chronic lymphocytic leukemia using microarray-based genomic profiling". doi:10.1186/1755-8166-7-3. PMC 3905918. PMID 24401281.CS1 maint: PMC format (link)
  10. 10.0 10.1 10.2 Cd, Schweighofer; et al. (2013). "Genomic variation by whole-genome SNP mapping arrays predicts time-to-event outcome in patients with chronic lymphocytic leukemia: a comparison of CLL and HapMap genotypes". doi:10.1016/j.jmoldx.2012.09.006. PMC 3586684. PMID 23273604.CS1 maint: PMC format (link)
  11. S, Fabris; et al. (2013). "Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia". PMID 23044996.
  12. F, Forconi; et al. (2008). "Genome-wide DNA analysis identifies recurrent imbalances predicting outcome in chronic lymphocytic leukaemia with 17p deletion". PMID 18752589.
  13. M, Jarosova; et al. (2010). "Gain of chromosome 2p in chronic lymphocytic leukemia: significant heterogeneity and a new recurrent dicentric rearrangement". PMID 20078324.
  14. 14.0 14.1 Ka, Kolquist; et al. (2011). "Evaluation of chronic lymphocytic leukemia by oligonucleotide-based microarray analysis uncovers novel aberrations not detected by FISH or cytogenetic analysis". doi:10.1186/1755-8166-4-25. PMC 3253687. PMID 22087757.CS1 maint: PMC format (link)
  15. I, Salaverria; et al. (2015). "Detection of chromothripsis-like patterns with a custom array platform for chronic lymphocytic leukemia". doi:10.1002/gcc.22277. PMC 4832286. PMID 26305789.CS1 maint: PMC format (link)
  16. N, Kawamata; et al. (2013). "Genetic differences between Asian and Caucasian chronic lymphocytic leukemia". doi:10.3892/ijo.2013.1966. PMC 3775563. PMID 23708256.CS1 maint: PMC format (link)
  17. K, Tsukasaki; et al. (2006). "Comparative genomic hybridization analysis of Japanese B-cell chronic lymphocytic leukemia: correlation with clinical course". PMID 16321855.
  18. 18.0 18.1 R, Gunnarsson; et al. (2011). "Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia". doi:10.3324/haematol.2010.039768. PMC 3148910. PMID 21546498.CS1 maint: PMC format (link)
  19. A, Cuneo; et al. (2004). "Chronic lymphocytic leukemia with 6q- shows distinct hematological features and intermediate prognosis". PMID 14712287.
  20. Dm, Wang; et al. (2011). "Intermediate prognosis of 6q deletion in chronic lymphocytic leukemia". PMID 21281237.
  21. M, Jarosova; et al. (2017). "Chromosome 6q deletion correlates with poor prognosis and low relative expression of FOXO3 in chronic lymphocytic leukemia patients". PMID 28699185.
  22. C, Nabhan; et al. (2015). "Predicting Prognosis in Chronic Lymphocytic Leukemia in the Contemporary Era". PMID 26181643.
  23. V, Grubor; et al. (2009). "Novel genomic alterations and clonal evolution in chronic lymphocytic leukemia revealed by representational oligonucleotide microarray analysis (ROMA)". PMID 18922857.
  24. 24.0 24.1 C, Schwaenen; et al. (2004). "Automated array-based genomic profiling in chronic lymphocytic leukemia: development of a clinical tool and discovery of recurrent genomic alterations". doi:10.1073/pnas.0304717101. PMC 327147. PMID 14730057.CS1 maint: PMC format (link)
  25. 25.0 25.1 25.2 25.3 Wg, Wierda; et al. (2017). "NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 1.2017". PMID 28275031.
  26. M, Dal Bo; et al. (2011). "13q14 deletion size and number of deleted cells both influence prognosis in chronic lymphocytic leukemia". PMID 21563234.
  27. 27.0 27.1 Sn, Malek (2013). "The biology and clinical significance of acquired genomic copy number aberrations and recurrent gene mutations in chronic lymphocytic leukemia". doi:10.1038/onc.2012.411. PMC 3676480. PMID 23001040.CS1 maint: PMC format (link)
  28. Pt, Greipp; et al. (2013). "Patients with chronic lymphocytic leukaemia and clonal deletion of both 17p13.1 and 11q22.3 have a very poor prognosis". doi:10.1111/bjh.12534. PMC 3907074. PMID 24032430.CS1 maint: PMC format (link)
  29. A, Cosson; et al. (2014). "14q deletions are associated with trisomy 12, NOTCH1 mutations and unmutated IGHV genes in chronic lymphocytic leukemia and small lymphocytic lymphoma". PMID 24729385.
  30. 30.0 30.1 R, Ibbotson; et al. (2012). "Coexistence of trisomies of chromosomes 12 and 19 in chronic lymphocytic leukemia occurs exclusively in the rare IgG-positive variant". PMID 21788947.
  31. Sr, Gunn; et al. (2008). "The HemeScan test for genomic prognostic marker assessment in chronic lymphocytic leukemia". PMID 23495782.
  32. H, Parker; et al. (2016). "Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia". doi:10.1038/leu.2016.134. PMC 5023049. PMID 27282254.CS1 maint: PMC format (link)
  33. 33.0 33.1 Hagenkord, Jill M.; et al. (2010-03). "Array-based karyotyping for prognostic assessment in chronic lymphocytic leukemia: performance comparison of Affymetrix 10K2.0, 250K Nsp, and SNP6.0 arrays". The Journal of molecular diagnostics: JMD. 12 (2): 184–196. doi:10.2353/jmoldx.2010.090118. ISSN 1943-7811. PMC 2871725. PMID 20075210. Check date values in: |date= (help)
  34. Pfeifer, Dietmar; et al. (2007-02-01). "Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP arrays". Blood. 109 (3): 1202–1210. doi:10.1182/blood-2006-07-034256. ISSN 0006-4971. PMID 17053054.
  35. 35.0 35.1 35.2 35.3 Edelmann, Jennifer; et al. (2012-12-06). "High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations". Blood. 120 (24): 4783–4794. doi:10.1182/blood-2012-04-423517. ISSN 1528-0020. PMID 23047824.
  36. Grygalewicz, Beata; et al. (2016). "Monoallelic and biallelic deletions of 13q14 in a group of CLL/SLL patients investigated by CGH Haematological Cancer and SNP array (8x60K)". Molecular Cytogenetics. 9: 1. doi:10.1186/s13039-015-0212-x. ISSN 1755-8166. PMC 4702365. PMID 26740820.
  37. Gunnarsson, Rebeqa; et al. (2011-08). "Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia". Haematologica. 96 (8): 1161–1169. doi:10.3324/haematol.2010.039768. ISSN 1592-8721. PMC 3148910. PMID 21546498. Check date values in: |date= (help)
  38. 38.0 38.1 38.2 Parker, H.; et al. (2011-03). "13q deletion anatomy and disease progression in patients with chronic lymphocytic leukemia". Leukemia. 25 (3): 489–497. doi:10.1038/leu.2010.288. ISSN 1476-5551. PMID 21151023. Check date values in: |date= (help)
  39. Lehmann, Sören; et al. (2008-03-15). "Molecular allelokaryotyping of early-stage, untreated chronic lymphocytic leukemia". Cancer. 112 (6): 1296–1305. doi:10.1002/cncr.23270. ISSN 0008-543X. PMID 18246537.
  40. Ouillette, Peter; et al. (2011-11-01). "The prognostic significance of various 13q14 deletions in chronic lymphocytic leukemia". Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. 17 (21): 6778–6790. doi:10.1158/1078-0432.CCR-11-0785. ISSN 1078-0432. PMC 3207001. PMID 21890456.
  41. 41.0 41.1 Stevens-Kroef, Marian Jpl; et al. (2014-01-09). "Identification of prognostic relevant chromosomal abnormalities in chronic lymphocytic leukemia using microarray-based genomic profiling". Molecular Cytogenetics. 7 (1): 3. doi:10.1186/1755-8166-7-3. ISSN 1755-8166. PMC 3905918. PMID 24401281.
  42. Saddler, Chris; et al. (2008-02-01). "Comprehensive biomarker and genomic analysis identifies p53 status as the major determinant of response to MDM2 inhibitors in chronic lymphocytic leukemia". Blood. 111 (3): 1584–1593. doi:10.1182/blood-2007-09-112698. ISSN 0006-4971. PMID 17971485.
  43. Pei, Jianming; et al. (2014-03). "Copy neutral loss of heterozygosity in 20q in chronic lymphocytic leukemia/small lymphocytic lymphoma". Cancer Genetics. 207 (3): 98–102. doi:10.1016/j.cancergen.2014.02.005. ISSN 2210-7762. PMC 4010307. PMID 24704113. Check date values in: |date= (help)
  44. Xu, Xinjie; et al. (2013-09). "The advantage of using SNP array in clinical testing for hematological malignancies--a comparative study of three genetic testing methods". Cancer Genetics. 206 (9–10): 317–326. doi:10.1016/j.cancergen.2013.09.001. ISSN 2210-7762. PMID 24269304. Check date values in: |date= (help)
  45. 45.0 45.1 Wierda, William G.; et al. (03 2017). "NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 1.2017". Journal of the National Comprehensive Cancer Network: JNCCN. 15 (3): 293–311. doi:10.6004/jnccn.2017.0030. ISSN 1540-1413. PMID 28275031. Check date values in: |date= (help)
  46. 46.0 46.1 Campregher, Paulo Vidal; et al. (2014-08). "Novel prognostic gene mutations identified in chronic lymphocytic leukemia and their impact on clinical practice". Clinical Lymphoma, Myeloma & Leukemia. 14 (4): 271–276. doi:10.1016/j.clml.2013.12.016. ISSN 2152-2669. PMID 24548608. Check date values in: |date= (help)
  47. 47.0 47.1 47.2 Strefford, Jonathan C. (2015-04). "The genomic landscape of chronic lymphocytic leukaemia: biological and clinical implications". British Journal of Haematology. 169 (1): 14–31. doi:10.1111/bjh.13254. ISSN 1365-2141. PMID 25496136. Check date values in: |date= (help)
  48. Alsolami, Reem; et al. (2013-06-01). "Clinical application of targeted and genome-wide technologies: can we predict treatment responses in chronic lymphocytic leukemia?". Personalized Medicine. 10 (4): 361–376. doi:10.2217/pme.13.33. ISSN 1741-0541. PMC 3943176. PMID 24611071.
  49. 49.0 49.1 49.2 Baliakas, P.; et al. (2015-02). "Recurrent mutations refine prognosis in chronic lymphocytic leukemia". Leukemia. 29 (2): 329–336. doi:10.1038/leu.2014.196. ISSN 1476-5551. PMID 24943832. Check date values in: |date= (help)
  50. 50.0 50.1 50.2 50.3 Rossi, Davide; et al. (2013-02-21). "Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia". Blood. 121 (8): 1403–1412. doi:10.1182/blood-2012-09-458265. ISSN 1528-0020. PMC 3578955. PMID 23243274.
  51. Rodríguez, David; et al. (2015-07-09). "Mutations in CHD2 cause defective association with active chromatin in chronic lymphocytic leukemia". Blood. 126 (2): 195–202. doi:10.1182/blood-2014-10-604959. ISSN 1528-0020. PMID 26031915.
  52. Wang, Lili; et al. (2011-12-29). "SF3B1 and other novel cancer genes in chronic lymphocytic leukemia". The New England Journal of Medicine. 365 (26): 2497–2506. doi:10.1056/NEJMoa1109016. ISSN 1533-4406. PMC 3685413. PMID 22150006.
  53. 53.0 53.1 Filip, Agata A. (2013-09). "New boys in town: prognostic role of SF3B1, NOTCH1 and other cryptic alterations in chronic lymphocytic leukemia and how it works". Leukemia & Lymphoma. 54 (9): 1876–1881. doi:10.3109/10428194.2013.769049. ISSN 1029-2403. PMID 23343182. Check date values in: |date= (help)
  54. Nabhan, Chadi; et al. (2015-10). "Predicting Prognosis in Chronic Lymphocytic Leukemia in the Contemporary Era". JAMA oncology. 1 (7): 965–974. doi:10.1001/jamaoncol.2015.0779. ISSN 2374-2445. PMID 26181643. Check date values in: |date= (help)
  55. Balatti, Veronica; et al. (2012-01-12). "NOTCH1 mutations in CLL associated with trisomy 12". Blood. 119 (2): 329–331. doi:10.1182/blood-2011-10-386144. ISSN 1528-0020. PMC 3257004. PMID 22086416.
  56. Del Giudice, Ilaria; et al. (2012-03). "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. doi:10.3324/haematol.2011.060129. ISSN 1592-8721. PMC 3291600. PMID 22207691. Check date values in: |date= (help)
  57. Herling, Carmen Diana; et al. (07 21, 2016). "Complex karyotypes and KRAS and POT1 mutations impact outcome in CLL after chlorambucil-based chemotherapy or chemoimmunotherapy". Blood. 128 (3): 395–404. doi:10.1182/blood-2016-01-691550. ISSN 1528-0020. PMID 27226433. Check date values in: |date= (help)
  58. Ramsay, Andrew J.; et al. (2013-05). "POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia". Nature Genetics. 45 (5): 526–530. doi:10.1038/ng.2584. ISSN 1546-1718. PMID 23502782. Check date values in: |date= (help)
  59. Speedy, Helen E.; et al. (11 10, 2016). "Germ line mutations in shelterin complex genes are associated with familial chronic lymphocytic leukemia". Blood. 128 (19): 2319–2326. doi:10.1182/blood-2016-01-695692. ISSN 1528-0020. PMC 5271173. PMID 27528712. Check date values in: |date= (help)
  60. Mitsui, Takeki; et al. (2016-02). "SF3B1 and IGHV gene mutation status predict poor prognosis in Japanese CLL patients". International Journal of Hematology. 103 (2): 219–226. doi:10.1007/s12185-015-1912-z. ISSN 1865-3774. PMID 26588928. Check date values in: |date= (help)
  61. Quesada, Víctor; et al. (2011-12-11). "Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia". Nature Genetics. 44 (1): 47–52. doi:10.1038/ng.1032. ISSN 1546-1718. PMID 22158541.
  62. Wan, Youzhong; et al. (2013-06-06). "SF3B1 mutations in chronic lymphocytic leukemia". Blood. 121 (23): 4627–4634. doi:10.1182/blood-2013-02-427641. ISSN 1528-0020. PMC 3674664. PMID 23568491.
  63. Rossi, Davide; et al. (2014-04-03). "Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia". Blood. 123 (14): 2139–2147. doi:10.1182/blood-2013-11-539726. ISSN 1528-0020. PMC 4017291. PMID 24501221.
  64. Zenz, Thorsten; et al. (2010-10-10). "TP53 mutation and survival in chronic lymphocytic leukemia". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 28 (29): 4473–4479. doi:10.1200/JCO.2009.27.8762. ISSN 1527-7755. PMID 20697090.
  65. Stilgenbauer, Stephan; et al. (2014-05-22). "Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial". Blood. 123 (21): 3247–3254. doi:10.1182/blood-2014-01-546150. ISSN 1528-0020. PMID 24652989.
  66. Cosson, A.; et al. (07 2017). "Gain in the short arm of chromosome 2 (2p+) induces gene overexpression and drug resistance in chronic lymphocytic leukemia: analysis of the central role of XPO1". Leukemia. 31 (7): 1625–1629. doi:10.1038/leu.2017.100. ISSN 1476-5551. PMID 28344316. Check date values in: |date= (help)
  67. Jain, Nitin; et al. (2015-07-23). "Initial treatment of CLL: integrating biology and functional status". Blood. 126 (4): 463–470. doi:10.1182/blood-2015-04-585067. ISSN 1528-0020. PMC 4624441. PMID 26065656.