Combination of all-trans retinoic acid and lithium chloride surmounts a retinoid differentiation block induced by expression of Scl and Rbtn2 transcription factors in myeloid leukemia cells.
We have previously shown that forced expression of the transcription factor Scl in WEHI-3B D(+) cells prevents ATRA-induced cell differentiation. We now find that the overexpression of Rbtn2 also interferes with induction of differentiation by ATRA. Addition of LiCl to ATRA treatment restored the capacity of both Scl- and Rbtn2-expressing cells to respond to the retinoid in a synergistic manner. Similar results were obtained with Scl-transfected HL60 cells where its expression diminished responsiveness to ATRA. These findings suggest that if Scl and/or Rbtn2 are involved in the non-responsiveness of AML patients to ATRA-induced differentiation, addition of LiCl may reverse insensitivity.
Rice
Anna M
AM
Department of Pharmacology and Developmental Therapeutics Program, Cancer Center, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Li
Jianming
J
Sartorelli
Alan C
AC
D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051792:Basic Helix-Loop-Helix Proteins; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D060588:LIM Domain Proteins; D007938:Leukemia / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology*; D008667:Metalloproteins / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*
D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D018021:Lithium Chloride; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D014212:Tretinoin; C085117:LMO2 protein, human; C067143:TAL1 protein, human