PMID- 26630574
OWN - NLM
STAT- MEDLINE
DCOM- 20160620
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 11
DP  - 2015
TI  - 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.
PG  - e0143073
LID - 10.1371/journal.pone.0143073 [doi]
LID - e0143073
AB  - 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 beta2M (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.
FAU - Hernandez, Jose Angel
AU  - Hernandez JA
AD  - Hematology Department, Hospital Universitario Infanta Leonor, Universidad 
      Complutense de Madrid, Madrid, Spain.
FAU - Hernandez-Sanchez, Maria
AU  - Hernandez-Sanchez M
AD  - IBSAL, IBMCC, Centro de Investigacion del Cancer, Universidad de Salamanca,CSIC, 
      Hospital Universitario de Salamanca, Spain.
FAU - Rodriguez-Vicente, Ana Eugenia
AU  - Rodriguez-Vicente AE
AD  - IBSAL, IBMCC, Centro de Investigacion del Cancer, Universidad de Salamanca,CSIC, 
      Hospital Universitario de Salamanca, Spain.
FAU - Grossmann, Vera
AU  - Grossmann V
AD  - MLL Munich, Germany.
FAU - Collado, Rosa
AU  - Collado R
AD  - Hematology Department, Hospital General, Valencia, Spain.
FAU - Heras, Cecilia
AU  - Heras C
AD  - Hematology Department, Hospital Universitario Infanta Leonor, Universidad 
      Complutense de Madrid, Madrid, Spain.
FAU - Puiggros, Anna
AU  - Puiggros A
AD  - Pathology Department, Hospital del Mar, Barcelona, Spain.
FAU - Martin, Ana Africa
AU  - Martin AA
AD  - Hematology Department, Hospital Universitario, Salamanca, Spain.
FAU - Puig, Noemi
AU  - Puig N
AD  - Hematology Department, Hospital Universitario, Salamanca, Spain.
FAU - Benito, Rocio
AU  - Benito R
AD  - IBSAL, IBMCC, Centro de Investigacion del Cancer, Universidad de Salamanca,CSIC, 
      Hospital Universitario de Salamanca, Spain.
FAU - Robledo, Cristina
AU  - Robledo C
AD  - IBSAL, IBMCC, Centro de Investigacion del Cancer, Universidad de Salamanca,CSIC, 
      Hospital Universitario de Salamanca, Spain.
FAU - Delgado, Julio
AU  - Delgado J
AD  - Hematology Department, Hospital Clinic i Provincial, Barcelona, Spain.
FAU - Gonzalez, Teresa
AU  - Gonzalez T
AD  - Fundacion Publica Galega de Medicina Xenomica, Santiago de Compostela, Spain.
FAU - Queizan, Jose Antonio
AU  - Queizan JA
AD  - Hematology Department, Hospital General, Segovia, Spain.
FAU - Galende, Josefina
AU  - Galende J
AD  - Hematology Department, Hospital del Bierzo, Ponferrada, Leon, Spain.
FAU - de la Fuente, Ignacio
AU  - de la Fuente I
AD  - Hematology Department, Hospital Universitario Rio Hortega, Valladolid, Spain.
FAU - Martin-Nunez, Guillermo
AU  - Martin-Nunez G
AD  - Hematology Department, Hospital Virgen del Puerto, Plasencia, Caceres, Spain.
FAU - Alonso, Jose Maria
AU  - Alonso JM
AD  - Hematology Department, Hospital Rio Carrion, Palencia, Spain.
FAU - Abrisqueta, Pau
AU  - Abrisqueta P
AD  - Hematology Department, Hospital Vall d'Hebron, Barcelona, Spain.
FAU - Luno, Elisa
AU  - Luno E
AD  - Hematology Department, Hospital Central de Asturias, Oviedo, Spain.
FAU - Marugan, Isabel
AU  - Marugan I
AD  - Hematology Department, Hospital Clinico, Valencia, Spain.
FAU - Gonzalez-Gascon, Isabel
AU  - Gonzalez-Gascon I
AD  - Hematology Department, Hospital Universitario Infanta Leonor, Universidad 
      Complutense de Madrid, Madrid, Spain.
FAU - Bosch, Francesc
AU  - Bosch F
AD  - Hematology Department, Hospital Vall d'Hebron, Barcelona, Spain.
FAU - Kohlmann, Alexander
AU  - Kohlmann A
AD  - MLL Munich, Germany.
AD  - AstraZeneca, Personalized Healthcare and Biomarkers, Innovative Medicines, 
      Macclesfield, United Kingdom.
FAU - Gonzalez, Marcos
AU  - Gonzalez M
AD  - IBSAL, IBMCC, Centro de Investigacion del Cancer, Universidad de Salamanca,CSIC, 
      Hospital Universitario de Salamanca, Spain.
AD  - Hematology Department, Hospital Universitario, Salamanca, Spain.
FAU - Espinet, Blanca
AU  - Espinet B
AD  - Pathology Department, Hospital del Mar, Barcelona, Spain.
FAU - Hernandez-Rivas, Jesus Maria
AU  - Hernandez-Rivas JM
AD  - IBSAL, IBMCC, Centro de Investigacion del Cancer, Universidad de Salamanca,CSIC, 
      Hospital Universitario de Salamanca, Spain.
AD  - Hematology Department, Hospital Universitario, Salamanca, Spain.
AD  - Department of Medicine, Universidad de Salamanca, Spain.
CN  - Grupo Cooperativo Espanol de Citogenetica Hematologica (GCECGH) and Grupo Espanol 
      de Leucemia Linfatica Cronica (GELLC)
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151202
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Immunoglobulin Heavy Chains)
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - *Chromosome Deletion
MH  - *Chromosomes, Human, Pair 11
MH  - Female
MH  - Gene Expression
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Immunoglobulin Heavy Chains/genetics
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotype
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*diagnosis/*genetics/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Neoplasm Proteins/*genetics/immunology
MH  - Prognosis
MH  - Retrospective Studies
MH  - Survival Analysis
PMC - PMC4667902
COIS- Competing Interests: The authors have declared that no competing interests exist. 
      Oligonucleotide primer plates for amplicon deep-sequencing were provided by Roche 
      Diagnostics, Penzberg, Germany, as part of the IRON-II study. VG and AK were 
      employed by MLL Munich Leukemia Laboratory and AK is employed by AstraZeneca. 
      This does not alter the authors' adherence to PLOS ONE policies on sharing data 
      and materials.
EDAT- 2015/12/03 06:00
MHDA- 2016/06/21 06:00
PMCR- 2015/12/02
CRDT- 2015/12/03 06:00
PHST- 2015/08/04 00:00 [received]
PHST- 2015/10/30 00:00 [accepted]
PHST- 2015/12/03 06:00 [entrez]
PHST- 2015/12/03 06:00 [pubmed]
PHST- 2016/06/21 06:00 [medline]
PHST- 2015/12/02 00:00 [pmc-release]
AID - PONE-D-15-34272 [pii]
AID - 10.1371/journal.pone.0143073 [doi]
PST - epublish
SO  - PLoS One. 2015 Dec 2;10(11):e0143073. doi: 10.1371/journal.pone.0143073. 
      eCollection 2015.