Abstract:
:Exogenous expression of the transcription factor Scl (Tal1) in WEHI-3B D+ myelomonocytic leukemia cells interferes with their capacity to respond to all-trans retinoic acid (ATRA) induced differentiation; combination of ATRA with LiCl, however, circumvents the inhibition of differentiation produced by Scl. To gain information on the possible involvement of this transcription factor in the non-responsiveness of acute myelocytic leukemia (AML) patients to ATRA, we compared the endogenous expression levels of Scl and its transcription complex partners [i.e., Rbtn1 (LMO1), Rbtn2 (LMO2), Ldb1, and GATA family proteins] in leukemic blast cells from patients with AML and acute promyelocytic leukemia (APL), and determined the effects of lithium chloride alone or in combination with ATRA on the capacity of blast cells to differentiate during short-term ex vivo culture. Levels of Scl, Rbtn2, GATA1, and Ldb1 expression were comparable in AML and APL blasts, while the levels of expression of Rbtn1, GATA2, and GATA3 were absent or markedly lower in APL cells. Differentiation markers (cell surface myeloid antigens CD11b, CD15, CD14, and CD33) were also analyzed in blast cells. ATRA produced changes in at least one surface antigen differentiation marker in 89% of patient blasts, while LiCl caused such changes in 72% of the leukemic cells of patients. The combination of LiCl and ATRA induced the differentiation of leukemic blasts from 94% of patients. Although the expression of the transcription factors did not act as individual predictors of responsiveness or non-responsiveness to the inducers of differentiation, ATRA or ATRA plus LiCl, the addition of LiCl to ATRA increased the differentiation response over that of ATRA alone in a number of leukemic samples. These findings suggest that the combination of LiCl and ATRA may produce some clinical benefit in the treatment of the myeloid leukemias.
journal_name
Leuk Resjournal_title
Leukemia researchauthors
Rice AM,Holtz KM,Karp J,Rollins S,Sartorelli ACdoi
10.1016/j.leukres.2004.03.017keywords:
subject
Has Abstractpub_date
2004-11-01 00:00:00pages
1227-37issue
11eissn
0145-2126issn
1873-5835pii
S0145212604001237journal_volume
28pub_type
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journal_title:Leukemia research
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doi:10.1016/j.leukres.2008.09.020
更新日期:2009-06-01 00:00:00
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doi:10.1016/j.leukres.2006.07.022
更新日期:2007-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/0145-2126(92)90139-x
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doi:10.1016/j.leukres.2008.04.001
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pub_type: 临床试验,杂志文章
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