PMID- 11746976
OWN - NLM
STAT- MEDLINE
DCOM- 20020110
LR  - 20191025
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 32
IP  - 4
DP  - 2001 Dec
TI  - Transcription factor BACH2 is transcriptionally regulated by the BCR/ABL 
      oncogene.
PG  - 353-63
AB  - Expression of BCR/ABL, a constitutively active tyrosine kinase, is a primary 
      event in the pathogenesis of chronic myeloid leukemia (CML) and Ph-positive acute 
      lymphoblastic leukemia (Ph+ALL). Inhibition of the BCR/ABL kinase activity in the 
      BV173 CML cell line with STI571 resulted in a significant overexpression of a 
      10-kb novel mRNA, found to be the human ortholog of the murine Bach2, a 
      B-cell-specific transcription factor. The human BACH2 cDNA is >9,120 bp long and 
      includes an open reading frame of 2,526 bp encoding a protein with a basic 
      leucine zipper (bZip) and a BTB/POZ domain, mediating DNA-binding and 
      heterodimerization. BACH2 was consistently upregulated (2-10-fold) in all 10 Ph+ 
      lymphoid lines tested following BCR/ABL inhibition. In CML myeloid cell lines (n 
      = 8) and BCR/ABL-negative lines (n = 6), BACH2 was either undetectable by 
      Northern blotting or did not change in response to STI571, suggesting that BACH2 
      repression by BCR/ABL may be specifically relevant to lymphoid transformation. 
      Quantitative RT/PCR revealed a significantly lower level of BACH2 expression in 
      leukocytes from patients with CML (n = 24) as compared to normal individuals (n = 
      23) (P < 0.0005). Moreover, CD34+ cells treated in vitro with STI571 exhibited a 
      consistent upregulation of BACH2 in 8 of 10 CMLs but in none of the 9 normal 
      individuals tested. Transcription regulation of BACH2 in BCR/ABL-positive cells 
      was exerted via the MEK pathways, as shown by their responses to the 
      U0126-specific inhibitor. Radiation hybrid mapping and FISH revealed that BACH2 
      is located on chromosome 6, band q15, a region frequently associated with 
      deletions in ALL and non-Hodgkin's lymphoma, suggesting its possible role as a 
      tumor suppressor gene. However, no rearrangement or loss of signal was observed 
      by Southern blotting in 34 lymphomas, 10 B-cell ALLs, or seven reactive lymph 
      nodes. The pattern of BACH2 expression in BCR/ABL-positive cells suggests that 
      transcriptional repression by this regulator is impaired in CML and may 
      contribute to the emergence of lymphoid blast crisis.
CI  - Copyright 2001 Wiley-Liss, Inc.
FAU - Vieira, S A
AU  - Vieira SA
AD  - Department of Haematology, Imperial College School of Medicine, Hammersmith 
      Hospital, London, UK.
FAU - Deininger, M W
AU  - Deininger MW
FAU - Sorour, A
AU  - Sorour A
FAU - Sinclair, P
AU  - Sinclair P
FAU - Foroni, L
AU  - Foroni L
FAU - Goldman, J M
AU  - Goldman JM
FAU - Melo, J V
AU  - Melo JV
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (BACH2 protein, human)
RN  - 0 (Basic-Leucine Zipper Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Adult
MH  - Basic-Leucine Zipper Transcription Factors
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 6/genetics
MH  - Cloning, Molecular
MH  - Exons
MH  - Fusion Proteins, bcr-abl/*genetics/physiology
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Rearrangement/genetics
MH  - Genes, abl/*physiology
MH  - HL-60 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Introns
MH  - K562 Cells
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics/metabolism/pathology
MH  - Lymphocytes/metabolism
MH  - Lymphoproliferative Disorders/genetics
MH  - Signal Transduction/genetics
MH  - Transcription Factors/biosynthesis/*genetics/*metabolism
MH  - Transcription, Genetic/*genetics
EDAT- 2001/12/18 10:00
MHDA- 2002/01/11 10:01
CRDT- 2001/12/18 10:00
PHST- 2001/12/18 10:00 [pubmed]
PHST- 2002/01/11 10:01 [medline]
PHST- 2001/12/18 10:00 [entrez]
AID - 10.1002/gcc.1200 [pii]
AID - 10.1002/gcc.1200 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2001 Dec;32(4):353-63. doi: 10.1002/gcc.1200.