Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact
Por:
Baliakas, P, Jeromin, S, Iskas, M, Puiggros, A, Plevova, K, Nguyen-Khac, F, Davis, Z, Rigolin, GM, Visentin, A, Xochelli, A, Delgado, J, Baran-Marszak, F, Stalika, E, Abrisqueta, P, Durechova, K, Papaioannou, G, Eclache, V, Dimou, M, Iliakis, T, Collado, R, Doubek, M, Calasanz, MJ, Ruiz-Xiville, N, Moreno, C, Jarosova, M, Leeksma, AC, Panayiotidis, P, Podgornik, H, Cymbalista, F, Anagnostopoulos, A, Trentin, L, Stavroyianni, N, Davi, F, Ghia, P, Kater, AP, Cuneo, A, Pospisilova, S, Espinet, B, Athanasiadou, A, Oscier, D, Haferlach, C, Stamatopoulos, K, ERIC European Res Initiative CLL
Publicada:
14 mar 2019
Resumen:
Recent evidence suggests that complex karyotype (CK) defined by the presence of >= 3 chromosomal aberrations (structural and/or numerical) identified by using chromosome-banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with >= 5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcomes, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and/or TP53 mutations [TP53abs]), and the expression of somatically hypermutated (M-CLL) or unmutated immunoglobulin heavy variable genes. Thus, they contrasted with CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and 112,119 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hyper-mutation status, we propose a novel hierarchical model in which patients with high-CK exhibit the worst prognosis, whereas those with mutated CLL lacking CK or TP53abs, as well as CK with 112,119, show the longest overall survival. Thus, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with >= 5 chromosomal aberrations emerges as prognostically adverse, independent of other biomarkers. Prospective clinical validation is warranted before ultimately incorporating high-CK in risk stratification of CLL.
Filiaciones:
Baliakas, P:
Uppsala Univ, Sci Life Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden
Jeromin, S:
Munich Leukemia Lab, Munich, Germany
Iskas, M:
G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece
G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece
Puiggros, A:
Hosp del Mar, Serv Patol, Lab Citogenet Mol, Barcelona, Spain
Inst Hosp del Mar Invest Med IMIM, Programa Recerca Canc, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain
Plevova, K:
Masaryk Univ, Cent European Inst Technol CEITEC, Brno, Czech Republic
Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic
Masaryk Univ, Fac Med, Brno, Czech Republic
Nguyen-Khac, F:
Hematol Dept, Paris, France
Sorbonne Univ, Hop Pitie Salpetriere, INSERM, U1138, Paris, France
Davis, Z:
Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England
Rigolin, GM:
St Anna Univ Hosp, Hematol Sect, Ferrara, Italy
Visentin, A:
Univ Padua, Dept Med, Hematol Div, Padua, Italy
Xochelli, A:
Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece
Delgado, J:
Univ Barcelona, Hosp Clin, Dept Hematol, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain
Baran-Marszak, F:
Hop Avicenne, Assistance Publ Hop Paris, Lab Hematol, Paris, France
Stalika, E:
Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece
Abrisqueta, P:
Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain
Durechova, K:
Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic
Masaryk Univ, Fac Med, Brno, Czech Republic
Papaioannou, G:
G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece
G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece
Eclache, V:
Hop Avicenne, Assistance Publ Hop Paris, Lab Hematol, Paris, France
Dimou, M:
Univ Athens, Laikon Univ Hosp, Dept Propedeut Internal Med 1, Hematol Sect, Athens, Greece
Iliakis, T:
Univ Athens, Laikon Univ Hosp, Dept Propedeut Internal Med 1, Hematol Sect, Athens, Greece
Collado, R:
Consorcio Hosp Gen Univ, Serv Hematol, Valencia, Spain
Doubek, M:
Masaryk Univ, Cent European Inst Technol CEITEC, Brno, Czech Republic
Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic
Masaryk Univ, Fac Med, Brno, Czech Republic
Calasanz, MJ:
Univ Navarra, Dept Genet, Serv Genet Citogenet, Pamplona, Spain
Ruiz-Xiville, N:
Univ Autonoma Barcelona, Inst Recerca Leucemia Josep Carreras IJC, ICO Hosp Germans Trias & Pujol, Serv Lab Hematol, Badalona, Spain
Moreno, C:
Hosp Univ Santa Creu & St Pau, Serv Hematol, Barcelona, Spain
Jarosova, M:
Masaryk Univ, Cent European Inst Technol CEITEC, Brno, Czech Republic
Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic
Masaryk Univ, Fac Med, Brno, Czech Republic
Leeksma, AC:
Univ Amsterdam, Acad Med Ctr Amsterdam, Dept Hematol & Lymphoma, Amsterdam, Netherlands
Univ Amsterdam, Acad Med Ctr Amsterdam, Myeloma Ctr Amsterdam, Amsterdam, Netherlands
Canc Ctr Amsterdam, Dept Expt Immunol, Amsterdam, Netherlands
Infect & Immun Inst Amsterdam, Amsterdam, Netherlands
Panayiotidis, P:
Univ Athens, Laikon Univ Hosp, Dept Propedeut Internal Med 1, Hematol Sect, Athens, Greece
Podgornik, H:
Univ Med Ctr Ljubljana, Dept Hematol, Ljubljana, Slovenia
Cymbalista, F:
Hop Avicenne, Assistance Publ Hop Paris, Lab Hematol, Paris, France
Anagnostopoulos, A:
G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece
G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece
Trentin, L:
Univ Padua, Dept Med, Hematol Div, Padua, Italy
Stavroyianni, N:
G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece
G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece
Davi, F:
Hematol Dept, Paris, France
Sorbonne Univ, Hop Pitie Salpetriere, INSERM, U1138, Paris, France
Ghia, P:
IRCCS San Raffaele Sci Inst, Div Expt Oncol, Strateg Res Program CLL, Milan, Italy
Univ Vita Salute San Raffaele, Milan, Italy
Kater, AP:
Univ Amsterdam, Acad Med Ctr Amsterdam, Dept Hematol & Lymphoma, Amsterdam, Netherlands
Univ Amsterdam, Acad Med Ctr Amsterdam, Myeloma Ctr Amsterdam, Amsterdam, Netherlands
Canc Ctr Amsterdam, Dept Expt Immunol, Amsterdam, Netherlands
Infect & Immun Inst Amsterdam, Amsterdam, Netherlands
Cuneo, A:
St Anna Univ Hosp, Hematol Sect, Ferrara, Italy
Pospisilova, S:
Masaryk Univ, Cent European Inst Technol CEITEC, Brno, Czech Republic
Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic
Masaryk Univ, Fac Med, Brno, Czech Republic
Espinet, B:
Hosp del Mar, Serv Patol, Lab Citogenet Mol, Barcelona, Spain
Inst Hosp del Mar Invest Med IMIM, Programa Recerca Canc, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain
Athanasiadou, A:
G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece
G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece
Oscier, D:
Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England
Haferlach, C:
Munich Leukemia Lab, Munich, Germany
Stamatopoulos, K:
Uppsala Univ, Sci Life Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden
Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece
Green Published, Bronze
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