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Ref Type Journal Article
PMID (23063977)
Authors Fujiki A, Imamura T, Sakamoto K, Kawashima S, Yoshida H, Hirashima Y, Miyachi M, Yagyu S, Nakatani T, Sugita K, Hosoi H
Title All-trans retinoic acid combined with 5-Aza-2'-deoxycitidine induces C/EBPα expression and growth inhibition in MLL-AF9-positive leukemic cells.
Journal Biochemical and biophysical research communications
Vol 428
Issue 2
Date 2012 Nov 16
URL
Abstract Text The present study tested whether all-trans retinoic acid (ATRA) and 5-Aza-2'-deoxycitidine (5-Aza) affect AML cell differentiation and growth in vitro by acting on the CCAAT/enhancer binding protein α (C/EBPα) and c-Myc axis. After exposure to a combination of these agents, cell differentiation and growth arrest were significantly higher in human and murine MLL-AF9-expressing cells than in MLL-AF4/AF5q31-expressing cells, which were partly associated with increased expression of C/EBPα, C/EBPε, and PU.1, and decreased expression of c-Myc. These findings indicate that MLL-AF9-expressing cells are more sensitive to ATRA and 5-Aza, indicating that different MLL fusion proteins possess different epigenetic properties associated with retinoic acid pathway inactivation.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KMT2A - AFF4 leukemia no benefit Decitabine + Tretinoin Preclinical - Cell culture Actionable In a preclinical study, combination treatment of Vesanoid (tretinoin) and Dacogen (decitabine) in murine leukemic cells expressing a KMT2A-AFF4 fusion did not result in upregulation of Mac-1 and C/EBPalpha and resulted in similar growth compared to untreated cells in culture (PMID: 23063977). 23063977
KMT2A - AFF1 acute myeloid leukemia predicted - sensitive Decitabine + Tretinoin Preclinical - Cell culture Actionable In a preclinical study, combination treatment of Vesanoid (tretinoin) and Dacogen (decitabine) resulted in growth inhibition in acute myeloid leukemia cells harboring a KMT2A-AFF1 fusion in cell culture (PMID: 23063977). 23063977
KMT2A - MLLT3 acute myeloid leukemia sensitive Decitabine + Tretinoin Preclinical - Cell culture Actionable In a preclinical study, combination of Vesanoid (tretinoin) and Dacogen (decitabine) in acute myeloid leukemia cells harboring KMT2A-MLLT3 resulted in significant growth inhibition, and greatly induced myeloid differentiation as indicated by CD11b and C/EBPalpha expression, and downregulation of c-Myc, and in a murine cell model, resulted in greater upregulation of C/EBPalpha and growth inhibition, and increased apoptosis compared to Tretinoin alone in culture (PMID: 23063977). 23063977
KMT2A - MLLT3 acute myeloid leukemia sensitive Tretinoin Preclinical - Cell culture Actionable In a preclinical study, treatment with Vesanoid (tretinoin) in acute myeloid leukemia cells harboring a KMT2A-MLLT3 fusion induced expression of myeloid differentiation markers, CD11b and PU.1, and resulted in growth inhibition, and in a murine cell model resulted in upregulation of Mac-1 and C/EBPalpha and growth inhibition in culture (PMID: 23063977). 23063977
KMT2A - AFF4 leukemia no benefit Tretinoin Preclinical - Cell culture Actionable In a preclinical study, treatment with Vesanoid (tretinoin) in murine leukemic cells expressing a KMT2A-AFF4 fusion did not result in upregulation of Mac-1 and C/EBPalpha and resulted in similar growth compared to untreated cells in culture (PMID: 23063977). 23063977