title: A Low Frequency of Losses in 11q Chromosome Is Associated with Better Outcome and Lower Rate of Genomic Mutations in Patients with Chronic Lymphocytic Leukemia.
abstract: To analyze the impact of the 11q deleted (11q-) cells in CLL patients on the time to first therapy (TFT) and overall survival (OS), 2,493 patients with CLL were studied. 242 patients (9.7%) had 11q-. Fluorescence in situ hybridization (FISH) studies showed a threshold of 40% of deleted cells to be optimal for showing that clinical differences in terms of TFT and OS within 11q- CLLs. In patients with ≥40% of losses in 11q (11q-H) (74%), the median TFT was 19 months compared with 44 months in CLL patients with <40% del(11q) (11q-L) (P<0.0001). In the multivariate analysis, only the presence of 11q-L, mutated IGHV status, early Binet stage and absence of extended lymphadenopathy were associated with longer TFT. Patients with 11q-H had an OS of 90 months, while in the 11q-L group the OS was not reached (P = 0.008). The absence of splenomegaly (P = 0.02), low LDH (P = 0.018) or β2M (P = 0.006), and the presence of 11q-L (P = 0.003) were associated with a longer OS. In addition, to detect the presence of mutations in the ATM, TP53, NOTCH1, SF3B1, MYD88, FBXW7, XPO1 and BIRC3 genes, a select cohort of CLL patients with losses in 11q was sequenced by next-generation sequencing of amplicons. Eighty % of CLLs with 11q- showed mutations and fewer patients with low frequencies of 11q- had mutations among genes examined (50% vs 94.1%, P = 0.023). In summary, CLL patients with <40% of 11q- had a long TFT and OS that could be associated with the presence of fewer mutated genes.
authors.affiliation: Hematology Department, Hospital Universitario Infanta Leonor, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: José Ángel
authors.initials: JÁ
authors.lastname: Hernández
authors.affiliation: IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca,CSIC, Hospital Universitario de Salamanca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Hernández-Sánchez
authors.affiliation: IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca,CSIC, Hospital Universitario de Salamanca, Spain.
authors.forename: Ana Eugenia
authors.initials: AE
authors.lastname: Rodríguez-Vicente
authors.affiliation: MLL Munich, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Grossmann
authors.affiliation: Hematology Department, Hospital General, Valencia, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Collado
authors.affiliation: Hematology Department, Hospital Universitario Infanta Leonor, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Heras
authors.affiliation: Pathology Department, Hospital del Mar, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Puiggros
authors.affiliation: Hematology Department, Hospital Universitario, Salamanca, Spain.
authors.forename: Ana África
authors.initials: AÁ
authors.lastname: Martín
authors.affiliation: Hematology Department, Hospital Universitario, Salamanca, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Puig
authors.affiliation: IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca,CSIC, Hospital Universitario de Salamanca, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Benito
authors.affiliation: IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca,CSIC, Hospital Universitario de Salamanca, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Robledo
authors.affiliation: Hematology Department, Hospital Clinic i Provincial, Barcelona, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Delgado
authors.affiliation: Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: González
authors.affiliation: Hematology Department, Hospital General, Segovia, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Queizán
authors.affiliation: Hematology Department, Hospital del Bierzo, Ponferrada, León, Spain.
authors.forename: Josefina
authors.initials: J
authors.lastname: Galende
authors.affiliation: Hematology Department, Hospital Universitario Río Hortega, Valladolid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: de la Fuente
authors.affiliation: Hematology Department, Hospital Virgen del Puerto, Plasencia, Cáceres, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Martín-Núñez
authors.affiliation: Hematology Department, Hospital Río Carrión, Palencia, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Alonso
authors.affiliation: Hematology Department, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Abrisqueta
authors.affiliation: Hematology Department, Hospital Central de Asturias, Oviedo, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Luño
authors.affiliation: Hematology Department, Hospital Clínico, Valencia, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Marugán
authors.affiliation: Hematology Department, Hospital Universitario Infanta Leonor, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: González-Gascón
authors.affiliation: Hematology Department, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Bosch
authors.affiliation: MLL Munich, Germany.|AstraZeneca, Personalized Healthcare and Biomarkers, Innovative Medicines, Macclesfield, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kohlmann
authors.affiliation: IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca,CSIC, Hospital Universitario de Salamanca, Spain.|Hematology Department, Hospital Universitario, Salamanca, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.affiliation: Pathology Department, Hospital del Mar, Barcelona, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Espinet
authors.affiliation: IBSAL, IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca,CSIC, Hospital Universitario de Salamanca, Spain.|Hematology Department, Hospital Universitario, Salamanca, Spain.|Department of Medicine, Universidad de Salamanca, Spain.
authors.forename: Jesús María
authors.initials: JM
authors.lastname: Hernández-Rivas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D005260:Female; D015870:Gene Expression; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D007143:Immunoglobulin Heavy Chains; D009363:Neoplasm Proteins