PMID- 21544632
OWN - NLM
STAT- MEDLINE
DCOM- 20120918
LR  - 20211020
IS  - 1559-131X (Electronic)
IS  - 1357-0560 (Linking)
VI  - 29
IP  - 2
DP  - 2012 Jun
TI  - Characterization of arsenic-induced cytogenetic alterations in acute 
      promyelocytic leukemia cell line, NB4.
PG  - 1209-16
LID - 10.1007/s12032-011-9946-4 [doi]
AB  - Gain or loss of genes plays important roles in leukemogenesis of APL via 
      cooperation with PML-RARA. Fluorescence in situ hybridization (FISH) was applied 
      to investigate the DNA copy number changes of hTERT, ERG, CDKN1B (P27), CDKN2A 
      (P16), and TP53 genes in an acute promyelocytic leukemia (APL) cell line (NB4). 
      Five bacterial artificial chromosome probes (BAC) for 9p21.3, 17p13.1, 12p13.2, 
      5p15.33, 21q22.2 regions were prepared using sequence independent amplification 
      (SIA) and were hybridized to NB4 cells treated with different doses of arsenic 
      trioxide (As(2)O(3); ATO) at various time intervals. NB4 cells were also 
      karyotyped by G-banded chromosome analysis 24 h after culture initiation. FISH 
      analysis prior to treatment showed CDKN1B, CDKN2A, and TP53 gene deletion but ERG 
      and hTERT gene amplification. After treatment with ATO, the number of the NB4 
      cells with deleted CDKN1B and CDKN2A as well as the counts of the cells with 
      hTERT amplification was significantly reduced in time- and does-dependent 
      manners. In addition, we observed expressive increase in signal patterns of 
      CDKN1B and CDKN2A along with significant decline in hTERT signal patterns in 
      ATO-treated cells as compared with the control group (in time- and dose-dependent 
      manners). On the other hand, no difference in signal patterns for Erg and p53 was 
      observed in response to ATO exposure. The results of the present study show the 
      cytogenetic alteration in hTERT, CDKN1B, and CDKN2A in NB4 cells after treatment 
      with ATO might introduce a new mechanism of antitumor activities of ATO in APL 
      cell line, NB4.
FAU - Yaghmaie, Marjan
AU  - Yaghmaie M
AD  - Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares 
      University, P.O.Box 14115-111, Tehran, Iran.
FAU - Mozdarani, Hossein
AU  - Mozdarani H
FAU - Alimoghaddam, Kamran
AU  - Alimoghaddam K
FAU - Ghaffari, Seyed Hamidullah
AU  - Ghaffari SH
FAU - Ghavamzadeh, Ardeshir
AU  - Ghavamzadeh A
FAU - Hajhashemi, Marjan
AU  - Hajhashemi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110505
PL  - United States
TA  - Med Oncol
JT  - Medical oncology (Northwood, London, England)
JID - 9435512
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Arsenicals)
RN  - 0 (Oxides)
RN  - S7V92P67HO (Arsenic Trioxide)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Arsenic Trioxide
MH  - Arsenicals/*pharmacology
MH  - Cell Survival/drug effects
MH  - Chromosome Aberrations/*chemically induced
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Promyelocytic, Acute/*drug therapy/*genetics/pathology
MH  - Neoplasm Recurrence, Local/drug therapy/genetics/pathology
MH  - Oxides/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 2011/05/06 06:00
MHDA- 2012/09/19 06:00
CRDT- 2011/05/06 06:00
PHST- 2011/02/24 00:00 [received]
PHST- 2011/04/04 00:00 [accepted]
PHST- 2011/05/06 06:00 [entrez]
PHST- 2011/05/06 06:00 [pubmed]
PHST- 2012/09/19 06:00 [medline]
AID - 10.1007/s12032-011-9946-4 [doi]
PST - ppublish
SO  - Med Oncol. 2012 Jun;29(2):1209-16. doi: 10.1007/s12032-011-9946-4. Epub 2011 May 
      5.