{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:05:04Z","timestamp":1762099504852},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2001,10,10]],"date-time":"2001-10-10T00:00:00Z","timestamp":1002672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2001,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Expression of BCR\/ABL, a constitutively active tyrosine kinase, is a primary event in the pathogenesis of chronic myeloid leukemia (CML) and Ph\u2010positive 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\u2010kb novel mRNA, found to be the human ortholog of the murine <jats:italic>Bach2<\/jats:italic>, a B\u2010cell\u2010specific transcription factor. The human <jats:italic>BACH2<\/jats:italic> cDNA is &gt;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\u2010binding and heterodimerization. <jats:italic>BACH2<\/jats:italic> was consistently upregulated (2\u201310\u2010fold) in all 10 Ph+ lymphoid lines tested following BCR\/ABL inhibition. In CML myeloid cell lines (n = 8) and <jats:italic>BCR\/ABL<\/jats:italic>\u2010negative lines (n = 6), <jats:italic>BACH2<\/jats:italic> was either undetectable by Northern blotting or did not change in response to STI571, suggesting that <jats:italic>BACH2<\/jats:italic> repression by <jats:italic>BCR\/ABL<\/jats:italic> may be specifically relevant to lymphoid transformation. Quantitative RT\/PCR revealed a significantly lower level of <jats:italic>BACH2<\/jats:italic> expression in leukocytes from patients with CML (n = 24) as compared to normal individuals (n = 23) (<jats:italic>P<\/jats:italic> &lt; 0.0005). Moreover, CD34+ cells treated in vitro with STI571 exhibited a consistent upregulation of <jats:italic>BACH2<\/jats:italic> in 8 of 10 CMLs but in none of the 9 normal individuals tested. Transcription regulation of <jats:italic>BACH2<\/jats:italic> in <jats:italic>BCR\/ABL<\/jats:italic>\u2010positive cells was exerted via the MEK pathways, as shown by their responses to the U0126\u2010specific inhibitor. Radiation hybrid mapping and FISH revealed that <jats:italic>BACH2<\/jats:italic> is located on chromosome 6, band q15, a region frequently associated with deletions in ALL and non\u2010Hodgkin'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\u2010cell ALLs, or seven reactive lymph nodes. The pattern of <jats:italic>BACH2<\/jats:italic> expression in <jats:italic>BCR\/ABL<\/jats:italic>\u2010positive cells suggests that transcriptional repression by this regulator is impaired in CML and may contribute to the emergence of lymphoid blast crisis. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.1200","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T21:15:54Z","timestamp":1030310154000},"page":"353-363","source":"Crossref","is-referenced-by-count":32,"title":["Transcription factor BACH2 is transcriptionally regulated by the <i>BCR\/ABL<\/i> oncogene"],"prefix":"10.1002","volume":"32","author":[{"given":"Sara A.D.","family":"Vieira","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael 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