PMID- 11712073
OWN - NLM
STAT- MEDLINE
DCOM- 20020306
LR  - 20190605
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 8
IP  - 6
DP  - 2001 Dec
TI  - Human bone marrow transplant rejection is associated with telomere cleavage.
PG  - 607-10
AB  - Telomeres that guard chromosomes are shortened with each cell division because of 
      replication-dependent sequence loss at both termini. The gradual erosion of 
      telomeric length has been directly related to the process of aging in vivo. 
      Recently we have reported, in murine and human cancer cells treated with 
      different apoptogens, cleavage and extrusion of telomeric DNA prior to cell death 
      on one hand and an amplification of telomeric DNA in metastatic epithelial 
      malignancies of different histopathologic origin on the other. This study tested 
      our hypothesis that telomere cleavage is linked to transplant rejection in cancer 
      patients receiving stem cells either from bone marrow (BM) or umbilical cord 
      blood transfusion. Telomere integrity and mitotic catastrophe were studied by 
      cytogenetic and molecular fluorescence in situ hybridization (FISH) techniques in 
      two BM samples taken from a male stem cell transplant recipient diagnosed with 
      aplastic anemia. The first BM sample, which was aspirated 27 days after 
      transplant, was mitotically active. Only one of 50 metaphases showed a chromatid 
      break. Every cell karyotyped was of male origin with 46, XY chromosome 
      constitution. The second BM sample aspirated 52 days after transplant gave no 
      metaphases and most interphase cells appeared dead. FISH preparations of the 
      second BM sample showed cleavage and drastic reduction of telomeric DNA at the 
      time the patient was rejecting the transplant. In contrast, the first BM sample 
      had shown no indication of cleavage of the telomeric DNA, although the percentage 
      of telomeric area was smaller than in the control. The replicative stress imposed 
      on the stem cells engrafted may result in an accelerated aging effect, possibly 
      due to the erosion of telomeric DNA. We, therefore, conclude that BM rejection 
      could be directly associated with the cleavage, clustering, and extrusion of 
      telomeric DNA in the donor cells.
FAU - Multani, A S
AU  - Multani AS
AD  - Department of Cancer Biology, The University of Texas M.D. Anderson Cancer 
      Center, Houston, TX 77030, USA.
FAU - Worth, L L
AU  - Worth LL
FAU - Jeha, S
AU  - Jeha S
FAU - Chan, K W
AU  - Chan KW
FAU - Pathak, S
AU  - Pathak S
LA  - eng
GR  - RRO 499901/RR/NCRR NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adolescent
MH  - *Bone Marrow Transplantation
MH  - DNA/genetics/metabolism
MH  - Graft Rejection/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Telomere/*genetics/metabolism
EDAT- 2001/11/17 10:00
MHDA- 2002/03/07 10:01
CRDT- 2001/11/17 10:00
PHST- 2001/11/17 10:00 [pubmed]
PHST- 2002/03/07 10:01 [medline]
PHST- 2001/11/17 10:00 [entrez]
AID - 10.3892/ijmm.8.6.607 [doi]
PST - ppublish
SO  - Int J Mol Med. 2001 Dec;8(6):607-10. doi: 10.3892/ijmm.8.6.607.