Karyotypic complexity rather than chromosome 8 abnormalities aggravates the outcome of chronic lymphocytic leukemia patients with TP53 aberrations.
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.
Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain.|Grup de Recerca Translacional en Neoplàsies Hematològiques, Cancer Research Programme, IMIM-Hospital del Mar, Barcelona, Spain.|Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Gonzalo
G
Blanco
Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain.|Grup de Recerca Translacional en Neoplàsies Hematològiques, Cancer Research Programme, IMIM-Hospital del Mar, Barcelona, Spain.
Anna
A
Puiggros
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Panagiotis
P
Baliakas
Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece.
Anastasia
A
Athanasiadou
Servicio de Hematología, Hospital Universitario Morales Meseguer, Murcia, Spain.
MªDolores
M
García-Malo
Servicio de Hematología, Consorcio Hospital General Universitario, Valencia, Spain.
Rosa
R
Collado
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.|Institute of Applied Biosciences, CERTH, Thessaloniki, Greece.
Aliki
A
Xochelli
Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain.|Grup de Recerca Translacional en Neoplàsies Hematològiques, Cancer Research Programme, IMIM-Hospital del Mar, Barcelona, Spain.
María
M
Rodríguez-Rivera
Laboratorio de Citogenética y Servicio de Hematología, Hospital Vall d'Hebron, Barcelona, Spain.
Margarita
M
Ortega
Servicio de Citogenética, Departamento de Genética, Universidad de Navarra, Pamplona, Spain.
Mª José
MJ
Calasanz
Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain.
Elisa
E
Luño
UGC de Hematología, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain.
MªTeresa
M
Vargas
Servei d'Hematologia, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain.
Javier
J
Grau
Laboratorio de Genética Hematológica, Servicio de Hematología, Hospital G.U. Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
Carolina
C
Martínez-Laperche
Servicios de Genética y Hematología, Complejo Hospitalario de Navarra, Pamplona, Spain.
Alberto
A
Valiente
Unidad de Genética, Hospital Universitario La Fe, Valencia, Spain.
José
J
Cervera
Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece.
Achilles
A
Anagnostopoulos
Servei d'Hematologia, Hospital del Mar, Barcelona, Spain.
Eva
E
Gimeno
Servei d'Hematologia, Hospital del Mar, Barcelona, Spain.
Eugènia
E
Abella
Institute of Applied Biosciences, CERTH, Thessaloniki, Greece.
Evangelia
E
Stalika
Servicio de Hematología, Hospital Universitario de Salamanca, IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca, CSIC, Salamanca, Spain.
Jesús Mª
JM
Hernández-Rivas
Servicio de Hematología, Hospital Universitario Morales Meseguer, Murcia, Spain.
Francisco José
FJ
Ortuño
Servicio de Hematología, Hospital Txagorritxu, Vitoria, Spain.
Diego
D
Robles
Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain.|Grup de Recerca Translacional en Neoplàsies Hematològiques, Cancer Research Programme, IMIM-Hospital del Mar, Barcelona, Spain.
Ana
A
Ferrer
Servicio de Hematología, Consorcio Hospital General Universitario, Valencia, Spain.
David
D
Ivars
Servicio de Hematología, Hospital Universitario de Salamanca, IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca, CSIC, Salamanca, Spain.
Marcos
M
González
Laboratorio de Citogenética y Servicio de Hematología, Hospital Vall d'Hebron, Barcelona, Spain.
Francesc
F
Bosch
Laboratorio de Citogenética y Servicio de Hematología, Hospital Vall d'Hebron, Barcelona, Spain.
Pau
P
Abrisqueta
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.|Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece.|Institute of Applied Biosciences, CERTH, Thessaloniki, Greece.
Kostas
K
Stamatopoulos
Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain.|Grup de Recerca Translacional en Neoplàsies Hematològiques, Cancer Research Programme, IMIM-Hospital del Mar, Barcelona, Spain.
Blanca
B
Espinet
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016009:Chi-Square Distribution; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D059785:Karyotype; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D010641:Phenotype; D016016:Proportional Hazards Models; D012307:Risk Factors; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
CLL; TP53 aberrations; chromosome 8 abnormalities; complex karyotype; prognosis