PMID- 20497575
OWN - NLM
STAT- MEDLINE
DCOM- 20100816
LR  - 20231105
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 10
DP  - 2010 May 24
TI  - The aberrant asynchronous replication - characterizing lymphocytes of cancer 
      patients - is erased following stem cell transplantation.
PG  - 230
LID - 10.1186/1471-2407-10-230 [doi]
AB  - BACKGROUND: Aberrations of allelic replication timing are epigenetic markers 
      observed in peripheral blood cells of cancer patients. The aberrant markers are 
      non-cancer-type-specific and are accompanied by increased levels of sporadic 
      aneuploidy. The study aimed at following the epigenetic markers and aneuploidy 
      levels in cells of patients with haematological malignancies from diagnosis to 
      full remission, as achieved by allogeneic stem cell transplantation (alloSCT). 
      METHODS: TP53 (a tumor suppressor gene assigned to chromosome 17), AML1 (a gene 
      assigned to chromosome 21 and involved in the leukaemia-abundant 8;21 
      translocation) and the pericentomeric satellite sequence of chromosome 17 (CEN17) 
      were used for replication timing assessments. Aneuploidy was monitored by 
      enumerating the copy numbers of chromosomes 17 and 21. Replication timing and 
      aneuploidy were detected cytogenetically using fluorescence in situ hybridization 
      (FISH) technology applied to phytohemagglutinin (PHA)-stimulated lymphocytes. 
      RESULTS: We show that aberrant epigenetic markers are detected in patients with 
      hematological malignancies from the time of diagnosis through to when they are 
      scheduled to undergo alloSCT. These aberrations are unaffected by the clinical 
      status of the disease and are displayed both during accelerated stages as well as 
      in remission. Yet, these markers are eradicated completely following stem cell 
      transplantation. In contrast, the increased levels of aneuploidy (irreversible 
      genetic alterations) displayed in blood lymphocytes at various stages of disease 
      are not eliminated following transplantation. However, they do not elevate and 
      remain unchanged (stable state). A demethylating anti-cancer drug, 5-azacytidine, 
      applied in vitro to lymphocytes of patients prior to transplantation mimics the 
      effect of transplantation: the epigenetic aberrations disappear while aneuploidy 
      stays unchanged. CONCLUSIONS: The reversible nature of the replication 
      aberrations may serve as potential epigenetic blood markers for evaluating the 
      success of transplant or other treatments and for long-term follow up of the 
      patients who have overcome a hematological malignancy.
FAU - Nagler, Arnon
AU  - Nagler A
AD  - Bone Marrow Transplantation Department, Institute of Hematology, Chaim Sheba 
      Medical Center, Tel-Hashomer 52621, Israel.
FAU - Cytron, Samuel
AU  - Cytron S
FAU - Mashevich, Maya
AU  - Mashevich M
FAU - Korenstein-Ilan, Avital
AU  - Korenstein-Ilan A
FAU - Avivi, Lydia
AU  - Avivi L
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100524
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (RUNX1 protein, human)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.1.1.- (DNA Modification Methylases)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aneuploidy
MH  - Azacitidine/pharmacology
MH  - Cells, Cultured
MH  - Child
MH  - Child, Preschool
MH  - Chromosomes, Human, Pair 17
MH  - Chromosomes, Human, Pair 21
MH  - Core Binding Factor Alpha 2 Subunit/genetics
MH  - DNA Modification Methylases/antagonists & inhibitors/metabolism
MH  - *DNA Replication Timing/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - *Epigenesis, Genetic/drug effects
MH  - Female
MH  - Hematologic Neoplasms/diagnosis/*genetics/pathology/*surgery
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lymphocytes/drug effects/*pathology
MH  - Male
MH  - Middle Aged
MH  - *Stem Cell Transplantation
MH  - Time Factors
MH  - Transplantation, Homologous
MH  - Treatment Outcome
MH  - Tumor Suppressor Protein p53/genetics
MH  - Young Adult
PMC - PMC2887401
EDAT- 2010/05/26 06:00
MHDA- 2010/08/17 06:00
PMCR- 2010/05/24
CRDT- 2010/05/26 06:00
PHST- 2009/09/14 00:00 [received]
PHST- 2010/05/24 00:00 [accepted]
PHST- 2010/05/26 06:00 [entrez]
PHST- 2010/05/26 06:00 [pubmed]
PHST- 2010/08/17 06:00 [medline]
PHST- 2010/05/24 00:00 [pmc-release]
AID - 1471-2407-10-230 [pii]
AID - 10.1186/1471-2407-10-230 [doi]
PST - epublish
SO  - BMC Cancer. 2010 May 24;10:230. doi: 10.1186/1471-2407-10-230.