Karyotypic complexity rather than chromosome 8 abnormalities aggravates the outcome of chronic lymphocytic leukemia patients with TP53 aberrations

Autor: Blanco, Gonzalo, Puiggros, Anna, Baliakas, Panagiotis, Athanasiadou, Anastasia, García-Malo, MaDolores, Collado, Rosa, Xochelli, Aliki, Rodríguez-Rivera, María, Ortega, Margarita, Calasanz, M.J, Luño, Elisa, Vargas, MªTeresa, Grau Cat, Javier, Martínez-Laperche, Carolina, Valiente, Alberto, Cervera, José, Anagnostopoulos, Achilles, Gimeno, Eva, Abella Monreal, Eugenia, Stalika, Evangelia, Hernández Rivas, Jesús María, Ortuño, Francisco José, Robles, Diego, Ferrer, Ana, Ivars, David, González, Marcos, Bosch José, Francesc Xavier, Abrisqueta, Pau, Stamatopoulos, Kostas, Espinet, Blanca, Universitat Autònoma de Barcelona
Přispěvatelé: Ministerio de Economía y Competitividad (España), European Commission, Generalitat de Catalunya, Fundación 'la Caixa', Instituto de Salud Carlos III, Swedish Research Council, Selander Foundation, Swedish Cancer Society, [Blanco, Gonzalo] Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain, [Puiggros, Anna] Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain, [Rodriguez-Rivera, Maria] Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain, [Ferrer, Ana] Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain, [Espinet, Blanca] Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain, [Blanco, Gonzalo] Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain, [Puiggros, Anna] Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain, [Rodriguez-Rivera, Maria] Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain, [Ferrer, Ana] Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain, [Espinet, Blanca] Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain, [Blanco, Gonzalo] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain, [Baliakas, Panagiotis] Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden, [Xochelli, Aliki] Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden, [Stamatopoulos, Kostas] Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden, [Athanasiadou, Anastasia] G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece, [Anagnostopoulos, Achilles] G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece, [Stamatopoulos, Kostas] G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece, [Athanasiadou, Anastasia] G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece, [Anagnostopoulos, Achilles] G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece, [Stamatopoulos, Kostas] G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece, [Garcia-Malo, MaDolores] Hosp Univ Morales Meseguer, Serv Hematol, Murcia, Spain, [Jose Ortuno, Francisco] Hosp Univ Morales Meseguer, Serv Hematol, Murcia, Spain, [Collado, Rosa] Consorcio Hosp Gen Univ, Serv Hematol, Valencia, Spain, [Ivars, David] Consorcio Hosp Gen Univ, Serv Hematol, Valencia, Spain, [Xochelli, Aliki] CERTH, Inst Appl Biosci, Thessaloniki, Greece, [Stalika, Evangelia] CERTH, Inst Appl Biosci, Thessaloniki, Greece, [Stamatopoulos, Kostas] CERTH, Inst Appl Biosci, Thessaloniki, Greece, [Ortega, Margarita] Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain, [Bosch, Francesc] Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain, [Abrisqueta, Pau] Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain, [Ortega, Margarita] Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain, [Bosch, Francesc] Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain, [Abrisqueta, Pau] Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain, [Jose Calasanz, Ma] Univ Navarra, Dept Genet, Serv Citogenet, Pamplona, Spain, [Luno, Elisa] Hosp Univ Cent Asturias, Serv Hematol, Oviedo, Spain, [Vargas, MaTeresa] Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBIS, UGC Hematol, Seville, Spain, [Grau, Javier] Univ Autonoma Barcelona, Inst Recerca Leucemia Josep Carreras IJC, ICO Hosp Germans Trias & Pujol, Serv Hematol, Badalona, Spain, [Martinez-Laperche, Carolina] Hosp GU Gregorio Maranon, Inst Invest Sanitaria Gregorio Maranon, Serv Hematol, Lab Genet Hematol, Madrid, Spain, [Valiente, Alberto] Complejo Hospitalario Navarra, Serv Genet & Hematol, Pamplona, Spain, [Cervera, Jose] Hosp Univ La Fe, Unidad Genet, Valencia, Spain, [Gimeno, Eva] Hosp del Mar, Serv Hematol, Barcelona, Spain, [Abella, Eugenia] Hosp del Mar, Serv Hematol, Barcelona, Spain, [Ma Hernandez-Rivas, Jesus] Univ Salamanca, Hosp Univ Salamanca, Ctr Invest Canc, CSIC,Serv Hematol,IBSAL,IBMCC, Salamanca, Spain, [Gonzalez, Marcos] Univ Salamanca, Hosp Univ Salamanca, Ctr Invest Canc, CSIC,Serv Hematol,IBSAL,IBMCC, Salamanca, Spain, [Robles, Diego] Hosp Txagorritxu, Serv Hematol, Vitoria, Spain, FEDER, Spanish Ministry of Economy and Competitiveness, Pla Director d'Oncologia de Catalunya (XBTC), Fundacio La Caixa, Lion's Cancer Research Foundation, Selander's Foundation, Uppsala, EU
Rok vydání: 2016
Předmět:
Hematology department
Male
complex karyotype
Predicts
Time Factors
17p deletion
Treatment outcome
Kaplan-Meier Estimate
Tp53 mutation
Leucèmia aguda -- Aspectes genètics
0302 clinical medicine
Risk Factors
Diagnosis
Chromosome 8 abnormalities
leucemia
Aged
80 and over
Leukemia
Progression
Leucèmia limfocítica
Middle Aged
TP53 aberrations
Prognosis
3. Good health
Phenotype
Treatment Outcome
Oncology
030220 oncology & carcinogenesis
Female
Chromosome Deletion
Mutations
Chromosomes
Human
Pair 8
Research Paper
Adult
medicine.medical_specialty
Karyotype
Guidelines
chromosome 8 abnormalities
Cytogenetics
03 medical and health sciences
medicine
Overall survival
Biomarkers
Tumor
Humans
Genetic Predisposition to Disease
Aged
Proportional Hazards Models
Gynecology
Cancer och onkologi
Chi-Square Distribution
business.industry
Complex karyotype
Leukemia
Lymphocytic
Chronic
B-Cell
Fish
Genes
Spain
Cancer and Oncology
Multivariate Analysis
Mutation
prognosis
Tumor Suppressor Protein p53
business
CLL
030215 immunology
Zdroj: GREDOS. Repositorio Institucional de la Universidad de Salamanca
instname
Oncotarget
r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
r-FISABIO: Repositorio Institucional de Producción Científica
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
r-FISABIO. Repositorio Institucional de Producción Científica
Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona
Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid
Consejería de Sanidad de la Comunidad de Madrid
Digital.CSIC. Repositorio Institucional del CSIC
Recercat. Dipósit de la Recerca de Catalunya
ISSN: 1949-2553
Popis: Patients with chronic lymphocytic leukemia (CLL) harboring TP53 aberrations (TP53abs; chromosome 17p deletion and/or TP53 mutation) exhibit an unfavorable clinical outcome. Chromosome 8 abnormalities, namely losses of 8p (8p-) and gains of 8q (8q+) have been suggested to aggravate the outcome of patients with TP53abs. However, the reported series were small, thus hindering definitive conclusions. To gain insight into this issue, we assessed a series of 101 CLL patients harboring TP53 disruption. The frequency of 8p- and 8q+ was 14.7% and 17.8% respectively. Both were associated with a significantly (P < 0.05) higher incidence of a complex karyotype (CK, ≥3 abnormalities) detected by chromosome banding analysis (CBA) compared to cases with normal 8p (N-8p) and 8q (N-8q), respectively. In univariate analysis for 10-year overall survival (OS), 8p- (P = 0.002), 8q+ (P = 0.012) and CK (P = 0.009) were associated with shorter OS. However, in multivariate analysis only CK (HR = 2.47, P = 0.027) maintained independent significance, being associated with a dismal outcome regardless of chromosome 8 abnormalities. In conclusion, our results highlight the association of chromosome 8 abnormalities with CK amongst CLL patients with TP53abs, while also revealing that CK can further aggravate the prognosis of this aggressive subgroup.
This work has been supported by the following grants: PI11/01621, PI15/00437, RD09/0076/00036, RD12/0036/0044, RD12/0036/0069 and PT13/0010/0005 FEDER, Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness; 2014/SGR585 from Generalitat de Catalunya; “Xarxa de Bancs de tumors” sponsored by Pla Director d'Oncologia de Catalunya (XBTC) and Fundació La Caixa; the Swedish Cancer Society, the Swedish Research Council, the Lion's Cancer Research Foundation, and Selander's Foundation, Uppsala; H2020 “AEGLE, An analytics framework for integrated and personalized healthcare services in Europe” by the EU.
Databáze: OpenAIRE
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