Retinoic acid is known to inhibit mammary carcinogenesis in rodents and to inhibit proliferation and steroid hormone receptor gene expression in human breast cancer cells. Since these effects are likely to be mediated by nuclear retinoic acid receptors (RARs) the present study was initiated to determine the expression and regulation of RARs in human breast cancer cell lines. Differential cellul...

phagic vesicles after treatment with these agents. Functionally, activation of autophagy by the mammalian target of rapamycin (mTOR) inhibitor triggers PML/RARA destabilization in the NB4 APL cell line, resulting in enhanced ATRA-induced differentiation. Conversely, the autophagy inhibitor BafA impedes treatment-induced PML/ RARA degradation and biologic response. These results are important in...

Acute promyelocitic leukemia (APL) is characterized by the pathognomonic presence in leukemic blasts of the hybrid protein PML/RARA, that acts as a transcriptional repressor impairing the expression of genes that are critical to myeloid differentiation. Here, we show that primary blasts from APL patients express lower levels of the oncosuppressor protein PTEN, as compared to blast cells from ot...

IN THE LATE 1980s and early 1990s, the elucidation of the molecular basis of acute promyelocytic leukemia (APL) emerged as a paradigm for the connection between the bench and bedside. At that time, it became apparent that APL was, among the forms of acute myeloid leukemia, uniquely sensitive to all-trans retinoic acid (ATRA)1,2 and clinical trials indicated that ATRA induced complete remissions...

A CUTE PROMYELOCYTIC leukemia (APL) has aroused interest well beyond the hematologic field during the last 4 to 5 years. Two features, both of which are unique to APL, have attracted the attention of various sectors of biomedical research: (1) the remission of the disease obtained with retinoic acid (RA) treatment, whose mechanism of action consists in inducing the APL blasts to differentiate t...

Acute promyelocytic leukemia (APL) is epitomized by the chromosomal translocation t(15;17) and the resulting oncogenic fusion protein PML-RARa. Although acting primarily as a transcriptional repressor, PML-RARa can also exert functions of transcriptional co-activation. Here, we find that PML-RARa stimulates transcription driven by HIF factors, which are critical regulators of adaptive responses...

To define the signal transduction pathway of retinoic acid during inner ear development, we analyzed the expression patterns of transcripts encoding the three retinoic acid receptors (RARa, b, and g) and related them to phenotypes resulting from single or compound inactivation of these nuclear receptors. The expression of all three RARs was observed in the developing mouse otocyst as early as e...

We characterized the enhancer landscape of 66 patients with acute myeloid leukemia (AML), identifying 6 novel subgroups and their associated regulatory loci. These subgroups are defined by their superenhancer (SE) maps, orthogonal to somatic mutations, and are associated with distinct leukemic cell states. Examination of transcriptional drivers for these epigenomic subtypes uncovers a subset of...

We reported previously that treatment with all-trans retinoic acid (ATRA) and granulocyte macrophage colony-stimulating factor (GMCSF) induces differentiation of human myeloblastic leukemia ML-1 cells to granulocytes, whereas treatment with ATRA alone induces practically no differentiation of these cells. To investigate the mechanism of the synergistic effect of these factors, we examined the e...

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Molecular methods for genomic analyses of variant PML-RARA or other RARA-related chromo-somal translocations in acute promyelocytic leukemia TO THE EDITOR: We read an interesting paper by Palta et al. in a recent issue of the Korean Journal of Hematology tit...