Association of Cytogenetics Aberrations and IGHV Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting

Muñoz-Novas Carolina, González-Gascón-y-Marín Isabel, Figueroa Iñigo, Sánchez-Paz Laura, Pérez-Carretero Claudia, Quijada-Álamo Miguel, Rodríguez-Vicente Ana-Eugenia, Infante María-Stefania, Foncillas María-Ángeles, Landete Elena, Churruca Juan, Marín Karen, Ramos Victoria, Sánchez Salto Alejandro, Hernández-Rivas José-Ángel

PDF(4554 KB)
PDF(4554 KB)
Global Medical Genetics ›› 2024, Vol. 11 ›› Issue (01) : 59-68. DOI: 10.1055/s-0044-1779668
Orginal Article
research-article

Association of Cytogenetics Aberrations and IGHV Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting

Author information +
History +

Keywords

chronic lymphocytic leukemia / IGHV mutation status / complex karyotype / overall survival / time to first treatment

Cite this article

Download citation ▾
Muñoz-Novas Carolina, González-Gascón-y-Marín Isabel, Figueroa Iñigo, Sánchez-Paz Laura, Pérez-Carretero Claudia, Quijada-Álamo Miguel, Rodríguez-Vicente Ana-Eugenia, Infante María-Stefania, Foncillas María-Ángeles, Landete Elena, Churruca Juan, Marín Karen, Ramos Victoria, Sánchez Salto Alejandro, Hernández-Rivas José-Ángel. Association of Cytogenetics Aberrations and IGHV Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting. Global Medical Genetics, 2024, 11(01): 59‒68 https://doi.org/10.1055/s-0044-1779668

References

[1]
Rozovski U, Hazan-Halevy I, Keating MJ, Estrov Z. Personalized medicine in CLL: current status and future perspectives. Cancer Lett 2014; 352(01) 4-14
[2]
Parikh SA. Chronic lymphocytic leukemia treatment algorithm 2018. Blood Cancer J 2018; 8(10) 93
[3]
Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood 1975; 46(02) 219-234
[4]
Binet JL, Auquier A, Dighiero G.et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 1981; 48(01) 198-206
[5]
Baliakas P, Iskas M, Gardiner A.et al. Chromosomal translocations and karyotype complexity in chronic lymphocytic leukemia: a systematic reappraisal of classic cytogenetic data. Am J Hematol 2014; 89(03) 249-255
[6]
Visentin A, Bonaldi L, Rigolin GM.et al. The combination of complex karyotype subtypes and IGHV mutational status identifies new prognostic and predictive groups in chronic lymphocytic leukaemia. Br J Cancer 2019; 121(02) 150-156
[7]
Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 1999; 94(06) 1848-1854
[8]
Damle RN, Wasil T, Fais F.et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999; 94(06) 1840-1847
[9]
Datta M, Jumaa H. Immunoglobulin gene sequence as an inherited and acquired risk factor for chronic lymphocytic leukemia. Cancers (Basel) 2022; 14(13) 3045
[10]
Fischer K, Bahlo J, Fink AM.et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood 2016; 127(02) 208-215
[11]
Rotbain EC, Frederiksen H, Hjalgrim H.et al. IGHV mutational status and outcome for patients with chronic lymphocytic leukemia upon treatment: a Danish nationwide population-based study. Haematologica 2020; 105(06) 1621-1629
[12]
International CLL-IPI working group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol 2016; 17(06) 779-790
[13]
Eichhorst B, Robak T, Montserrat E.et al; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2021; 32(01) 23-33
[14]
NCCN Clinical Practice Guidelines in Oncology. (NCCN Guidelines ®). Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma [Internet]. 2023 [Accessed June 7, 2023]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf
[15]
Couillez G, Morel P, Clichet V.et al. Flow cytometry as a fast, cost-effective tool to assess IGHV mutational status in CLL. Blood Adv 2023; 7(17) 4701-4704
[16]
16 González-Gascón Y Marín I, Hernández JA, Martín A.et al. Mutation status and immunoglobulin gene rearrangements in patients from northwest and central region of Spain with chronic lymphocytic leukemia. BioMed Res Int 2014; 2014: 257517
[17]
Marinelli M, Ilari C, Xia Y.et al. Immunoglobulin gene rearrangements in Chinese and Italian patients with chronic lymphocytic leukemia. Oncotarget 2016; 7(15) 20520-20531
[18]
Chen L, Zhang Y, Zheng W.et al. Distinctive IgVH gene segments usage and mutation status in Chinese patients with chronic lymphocytic leukemia. Leuk Res 2008; 32(10) 1491-1498
[19]
Ghia P, Stamatopoulos K, Belessi C.et al. Geographic patterns and pathogenetic implications of IGHV gene usage in chronic lymphocytic leukemia: the lesson of the IGHV3-21 gene. Blood 2005; 105(04) 1678-1685
[20]
Bomben R, Dal Bo M, Capello D.et al. Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study. Blood 2007; 109(07) 2989-2998
[21]
Raponi S, Ilari C, Della Starza I.et al. Redefining the prognostic likelihood of chronic lymphocytic leukaemia patients with borderline percentage of immunoglobulin variable heavy chain region mutations. Br J Haematol 2020; 189(05) 853-859
[22]
Harris NL, Jaffe ES, Diebold J.et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 1999; 17(12) 3835-3849
[23]
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 2008; 111(12) 5446-5456
[24]
Ghia P, Stamatopoulos K, Belessi C.et al; European Research Initiative on CLL. ERIC recommendations on IGHV gene mutational status analysis in chronic lymphocytic leukemia. Leukemia 2007; 21(01) 1-3
[25]
Kreinitz N, Polliack A, Tadmor T. Chronic lymphocytic leukemia is becoming more complex: how to define complex karyotype?. Leuk Lymphoma 2018; 59(03) 521-522
[26]
Baliakas P, Jeromin S, Iskas M.et al; ERIC, the European Research Initiative on CLL. Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact. Blood 2019; 133(11) 1205-1216
[27]
Guo A, Lu P, Galanina N.et al. Heightened BTK-dependent cell proliferation in unmutated chronic lymphocytic leukemia confers increased sensitivity to ibrutinib. Oncotarget 2016; 7(04) 4598-4610
[28]
Stamatopoulos B, Smith T, Crompot E.et al. The light chain IgLV3-21 defines a new poor prognostic subgroup in chronic lymphocytic leukemia: results of a multicenter study. Clin Cancer Res 2018; 24(20) 5048-5057
[29]
Urbanova R, Humplikova L, Drimalova H.et al. Biological and clinical characteristics of patients with chronic lymphocytic leukemia with the IGHV3-21 and IGHV1-69; analysis of data from a single center. Neoplasma 2015; 62(04) 618-626
[30]
Cahill N, Sutton LA, Jansson M.et al. IGHV3-21 gene frequency in a Swedish cohort of patients with newly diagnosed chronic lymphocytic leukemia. Clin Lymphoma Myeloma Leuk 2012; 12(03) 201-206
[31]
Baliakas P, Agathangelidis A, Hadzidimitriou A.et al. Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations. Blood 2015; 125(05) 856-859
[32]
Thorsélius M, Kröber A, Murray F.et al. Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status. Blood 2006; 107(07) 2889-2894
[33]
Kryachok I, Abramenko I, Bilous N, Chumak A, Martina Z, Filonenko I. IGHV gene rearrangements as outcome predictors for CLL patients: experience of Ukrainian group. Med Oncol 2012; 29(02) 1093-1101
[34]
Potter KN, Orchard J, Critchley E, Mockridge CI, Jose A, Stevenson FK. Features of the overexpressed V1-69 genes in the unmutated subset of chronic lymphocytic leukemia are distinct from those in the healthy elderly repertoire. Blood 2003; 101(08) 3082-3084
[35]
Panovska-Stavridis I, Ivanovski M, Siljanovski N, Cevreska L, Efremov DG. Chronic lymphocytic leukemia patients with a V1-69 gene rearrangement do not have inferior survival with respect to patients that express other unmutated V(H) genes. Leuk Res 2007; 31(02) 245-248
[36]
Sutton LA, Kostareli E, Hadzidimitriou A.et al. Extensive intraclonal diversification in a subgroup of chronic lymphocytic leukemia patients with stereotyped IGHV4-34 receptors: implications for ongoing interactions with antigen. Blood 2009; 114(20) 4460-4468
[37]
Stanganelli C, Torres DC, Ortega C.et al. Somatic hypermutation profiles in stereotyped IGHV4-34 receptors from South American chronic lymphocytic leukemia patients. Ann Hematol 2022; 101(02) 341-348
[38]
Karan-Djurasevic T, Palibrk V, Kostic T.et al. Mutational status and gene repertoire of IGHV-IGHD-IGHJ rearrangements in Serbian patients with chronic lymphocytic leukemia. Clin Lymphoma Myeloma Leuk 2012; 12(04) 252-260
[39]
Sandoval-Sus JD, Chavez JC, Dalia S.et al. Association between immunoglobulin heavy-chain variable region mutational status and isolated favorable baseline genomic aberrations in chronic lymphocytic leukemia. Leuk Lymphoma 2018; 59(01) 59-68
[40]
Gladstone DE, Swinnen L, Kasamon Y.et al. Importance of immunoglobulin heavy chain variable region mutational status in del(13q) chronic lymphocytic leukemia. Leuk Lymphoma 2011; 52(10) 1873-1881
[41]
Kharfan-Dabaja MA, Chavez JC, Khorfan KA, Pinilla-Ibarz J. Clinical and therapeutic implications of the mutational status of IgVH in patients with chronic lymphocytic leukemia. Cancer 2008; 113(05) 897-906
[42]
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(01) 105-113
[43]
Rigolin GM, Cavallari M, Quaglia FM.et al. In CLL, comorbidities and the complex karyotype are associated with an inferior outcome independently of CLL-IPI. Blood 2017; 129(26) 3495-3498
[44]
Rigolin GM, del Giudice I, Formigaro L.et al. Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia: clinical and biologic correlations. Genes Chromosomes Cancer 2015; 54(12) 818-826
[45]
Heerema NA, Muthusamy N, Zhao Q.et al. Prognostic significance of translocations in the presence of mutated IGHV and of cytogenetic complexity at diagnosis of chronic lymphocytic leukemia. Haematologica 2021; 106(06) 1608-1615
[46]
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
[47]
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
[48]
Nabhan C, Raca G, Wang YL. Predicting prognosis in chronic lymphocytic leukemia in the contemporary era. JAMA Oncol 2015; 1(07) 965-974

RIGHTS & PERMISSIONS

2024 Global Medical Genetics
PDF(4554 KB)

Accesses

Citations

Detail

Sections
Recommended

/