PMID- 24032430
OWN - NLM
STAT- MEDLINE
DCOM- 20131203
LR  - 20211021
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 163
IP  - 3
DP  - 2013 Nov
TI  - Patients with chronic lymphocytic leukaemia and clonal deletion of both 17p13.1 
      and 11q22.3 have a very poor prognosis.
PG  - 326-33
LID - 10.1111/bjh.12534 [doi]
AB  - Detection of a 17p13.1 deletion (loss of TP53) or 11q22.3 deletion (loss of ATM), 
      by fluorescence in situ hybridization (FISH), in chronic lymphocytic leukaemia 
      (CLL) patients is associated with a poorer prognosis. Because TP53 and ATM are 
      integral to the TP53 pathway, we hypothesized that 17p13.1- (17p-) and 11q22.3- 
      (11q-) occurring in the same cell (clonal 17p-/11q-) would confer a worse 
      prognosis than either 17p- or 11q-. We studied 2184 CLL patients with FISH 
      (1995-2012) for the first occurrence of 17p-, 11q-, or clonal 17p-/11q-. Twenty 
      (1%) patients had clonal 17p-/11q-, 158 (7%) had 17p- (including 4 with 17p- and 
      11q- in separate clones), 247 (11%) had 11q-, and 1759 (81%) had neither 17p- nor 
      11q-. Eleven of 15 (73%) tested patients with clonal 17p-/11q- had dysfunctional 
      TP53 mutations. Overall survival for clonal 17p-/11q- was significantly shorter 
      (1.9 years) than 17p- (3.1 years, P = 0.04), 11q- (4.8 years, P </= 0.0001), or 
      neither 17p- nor 11q- (9.3 years, P </= 0.0001). Clonal 17p-/11q- thus conferred 
      significantly worse prognosis, suggesting that loss of at least one copy of both 
      TP53 and ATM causes more aggressive disease. Use of an ATM/TP53 combination FISH 
      probe set could identify these very-high risk patients.
CI  - (c) 2013 John Wiley & Sons Ltd.
FAU - Greipp, Patricia T
AU  - Greipp PT
AD  - Department of Laboratory Medicine and Pathology, Cytogenetics Laboratory, Mayo 
      Clinic College of Medicine, Rochester, MN, USA.
FAU - Smoley, Stephanie A
AU  - Smoley SA
FAU - Viswanatha, David S
AU  - Viswanatha DS
FAU - Frederick, Lori S
AU  - Frederick LS
FAU - Rabe, Kari G
AU  - Rabe KG
FAU - Sharma, Ruchi G
AU  - Sharma RG
FAU - Slager, Susan L
AU  - Slager SL
FAU - Van Dyke, Daniel L
AU  - Van Dyke DL
FAU - Shanafelt, Tait D
AU  - Shanafelt TD
FAU - Tschumper, Renee C
AU  - Tschumper RC
FAU - Zent, Clive S
AU  - Zent CS
LA  - eng
GR  - N01 CA015083/CA/NCI NIH HHS/United States
GR  - P30 CA015083/CA/NCI NIH HHS/United States
GR  - P50 CA097274/CA/NCI NIH HHS/United States
GR  - CA CA97274/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130827
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Neoplasm Proteins)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.11.1 (ATM protein, human)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Ataxia Telangiectasia Mutated Proteins/deficiency/genetics
MH  - *Chromosome Deletion
MH  - Chromosomes, Human, Pair 11/*ultrastructure
MH  - Chromosomes, Human, Pair 17/*ultrastructure
MH  - Clone Cells/ultrastructure
MH  - Female
MH  - Genes, Neoplasm
MH  - Genes, Tumor Suppressor
MH  - Genes, p53
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Kaplan-Meier Estimate
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/classification/*genetics/mortality
MH  - Lymphocytes/ultrastructure
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Proteins/deficiency/genetics
MH  - Prognosis
MH  - Retrospective Studies
MH  - Tumor Suppressor Protein p53/deficiency
PMC - PMC3907074
MID - NIHMS515263
OTO - NOTNLM
OT  - ATM
OT  - TP53
OT  - chronic lymphocytic leukaemia
OT  - fluorescence in situ hybridization (FISH)
OT  - prognostic factors
EDAT- 2013/09/17 06:00
MHDA- 2013/12/16 06:00
PMCR- 2014/11/01
CRDT- 2013/09/17 06:00
PHST- 2013/05/03 00:00 [received]
PHST- 2013/07/19 00:00 [accepted]
PHST- 2013/09/17 06:00 [entrez]
PHST- 2013/09/17 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2014/11/01 00:00 [pmc-release]
AID - 10.1111/bjh.12534 [doi]
PST - ppublish
SO  - Br J Haematol. 2013 Nov;163(3):326-33. doi: 10.1111/bjh.12534. Epub 2013 Aug 27.