PMID- 24334759
OWN - NLM
STAT- MEDLINE
DCOM- 20141204
LR  - 20211021
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 5
IP  - 1
DP  - 2014 Jan 15
TI  - Genetic subclonal complexity and miR125a-5p down-regulation identify a subset of 
      patients with inferior outcome in low-risk CLL patients.
PG  - 140-9
AB  - The majority of patients with chronic lymphocytic leukemia (CLL) and favorable 
      prognostic features live for long periods without treatment. However, unexpected 
      disease progression is observed in some cases. In a cohort of untreated CD38- CLL 
      patients with normal FISH or isolated 13q- we found that, by fluorescence in situ 
      hybridization (FISH), 16/28 cases presented, within immunomagnetic sorted CD38+ 
      cells, genetic lesions undetectable in the CD38- fraction. These patients showed 
      a shorter time to first treatment (TTFT, p=0.0162) in comparison to cases without 
      FISH lesions in CD38+ cells. Patients with FISH abnormalities in CD38+ cells 
      showed a distinctive microRNA profile, characterized by the down-regulation of 
      miR-125a-5p both in the CD38- and CD38+ populations. In an independent cohort of 
      71 consecutive untreated CD38- CLL with normal FISH or isolated 13q-, a lower 
      miR125a-5p expression was associated with a shorter TTFT both in univariate and 
      multivariate analysis (p=0.003 and 0.016, respectively) and with a higher 
      prevalence of mutations (7/12 vs 0/8, p=0.015) as assessed by next-generation 
      sequencing. In conclusion, our data showed previously unrecognized subclonal 
      heterogeneity within the CD38+ fraction of CD38- CLL patients with low-risk FISH 
      findings and suggested an association between down-regulated miR-125a-5p 
      expression, genetic complexity and worse outcome.
FAU - Rigolin, Gian Matteo
AU  - Rigolin GM
AD  - Hematology Section, Department of Medical Sciences, University of Ferrara, 
      University Hospital Arcispedale S. Anna, Ferrara, Italy.
FAU - Saccenti, Elena
AU  - Saccenti E
FAU - Rizzotto, Lara
AU  - Rizzotto L
FAU - Ferracin, Manuela
AU  - Ferracin M
FAU - Martinelli, Sara
AU  - Martinelli S
FAU - Formigaro, Luca
AU  - Formigaro L
FAU - Cibien, Francesca
AU  - Cibien F
FAU - Cavallari, Maurizio
AU  - Cavallari M
FAU - Lista, Enrico
AU  - Lista E
FAU - Daghia, Giulia
AU  - Daghia G
FAU - Sofritti, Olga
AU  - Sofritti O
FAU - Ciccone, Maria
AU  - Ciccone M
FAU - Cavazzini, Francesco
AU  - Cavazzini F
FAU - Lupini, Laura
AU  - Lupini L
FAU - Bassi, Cristian
AU  - Bassi C
FAU - Zagatti, Barbara
AU  - Zagatti B
FAU - Negrini, Massimo
AU  - Negrini M
FAU - Cuneo, Antonio
AU  - Cuneo A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (MicroRNAs)
RN  - EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
SB  - IM
MH  - ADP-ribosyl Cyclase 1/genetics/metabolism
MH  - Aged
MH  - Aged, 80 and over
MH  - Cluster Analysis
MH  - Cohort Studies
MH  - DNA Mutational Analysis
MH  - Down-Regulation
MH  - Female
MH  - Humans
MH  - Immunomagnetic Separation
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*genetics
MH  - Male
MH  - MicroRNAs/genetics/*metabolism
MH  - Middle Aged
MH  - Prognosis
MH  - Treatment Outcome
PMC - PMC3960196
COIS- The authors declare no competing financial interests.
EDAT- 2013/12/18 06:00
MHDA- 2014/12/15 06:00
PMCR- 2014/01/01
CRDT- 2013/12/17 06:00
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - 1382 [pii]
AID - 10.18632/oncotarget.1382 [doi]
PST - ppublish
SO  - Oncotarget. 2014 Jan 15;5(1):140-9. doi: 10.18632/oncotarget.1382.