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| Histone deacetylase-targeted treatment restores retinoic acid signaling and differentiation in acute myeloid leukemia |
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| Author(s): Ferrara FF, Fazi F, Bianchini A, Padula F, Gelmetti V, Minucci S, Mancini M, Pelicci PG, Lo Coco F, Nervi C |
| Source: CANCER RESEARCH Volume: 61 Issue: 1 Pages: 2-7 Published: JAN 1 2001 |
| Times Cited: 179 References: 33 |
| Abstract: Histone deacetylase (HDAC)-dependent transcriptional repression of the retinoic acid (RA)-signaling pathway underlies the differentiation block of acute promyelocytic leukemia. RA treatment relieves transcriptional repression and triggers differentiation of acute promyelocytic leukemia blasts, leading to disease remission. We report that transcriptional repression of RA signaling is a common mechanism in acute myeloid leukemias (AMLs). HDAC inhibitors restored RA-dependent transcriptional activation and triggered terminal differentiation of primary blasts from 23 AML patients. Accordingly, we show that AML1/ETO, the commonest AML-associated fusion protein, is an HDAC-dependent repressor of RA signaling. These findings relate alteration of the RA pathway to myeloid leukemogenesis and underscore the potential of transcriptional/ differentiation therapy in AML. |
| Document Type: Article |
| Language: English |
| Reprint Address: Nervi, C (reprint author), Univ Rome La Sapienza, Dept Histol & Med Embryol, Piazzale Aldo Moro 5, I-00161 Rome, Italy |
Addresses:
1. Univ Rome La Sapienza, Dept Histol & Med Embryol, I-00161 Rome, Italy
2. Univ Rome La Sapienza, Dept Cellular Biotechnol & Hematol, I-00161 Rome, Italy
3. European Inst Oncol, Dept Expt Oncol, I-20141 Milan, Italy
4. Inst Internal Med & Oncol Sci, I-06100 Perugia, Italy |
| Publisher: AMER ASSOC CANCER RESEARCH, PO BOX 11806, BIRMINGHAM, AL 35202 USA |
| Subject Category: Oncology |
| IDS Number: 392WR |
| ISSN: 0008-5472 |
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