Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q11.2), which results in the PML-RARA fusion gene. In previous studies, we demonstrated that expression of a human PML-RARA complementary DNA in murine granulocyte precursor cells initiated the development of leukemia. However, leukemogenesis by PML-RARA required additional genetic alterations. To identify genetic changes t...

The X-RARA fusion proteins have reduced sensitivity to all-transretinoic acid (ATRA), and have been proposed to act by decreasing retinoid-dependent transcription required for myeloid maturation. We therefore sought to determine whether maturing myeloid cells are exposed to natural retinoid ligands in vivo. Surprisingly, we detected a paucity of natural retinoids capable of transactivating RARA...

Rapid diagnosis of acute promyelocytic leukemia (APL) with promyelocytic leukemia-retinoic acid receptor alpha (PML-RARa) contributes to a highly effective therapy with all-trans retinoic acid (ATRA). Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) is a valuable tool to diagnose APL with PML-RARa. However, a single RT-qPCR analysis, which is laborious and costly...

Typical acute promyelocytic leukemia (APL) is associated with expression of the PML-RARa fusion protein and responsiveness to treatment with all-trans retinoic acid (ATRA). A rare, but recurrent, APL has been described that does not respond to ATRA treatment and is associated with a variant chromosomal translocation and expression of the PLZFRARa fusion protein. Both PMLand PLZF-RARa possess id...

Retinoic acid receptor (RAR) a has been shown to play a role in retinoid-induced growth Inhibition of human breast cancer cell lines that express the estrogen receptor (ER). The dogma in the field has been that ER-positive breast cancer cell lines respond to retinoid treatment because they express RARa, whereas ER-negative breast cancer cell lines are refractory to retinold treatment and have b...

PURPOSE The Retinoic Acid Receptor Alpha (RARA) gene is a potential candidate gene for myopia due to its differential expression in animal models during experimentally induced myopia. To test for whether RARA is associated with myopia we have undertaken a case-control study assessing for associations between RARA and myopia, hypermetropia, and ocular biometric measures. METHODS A total of 802...

Retinoic acid (RA) is involved in hematopoiesis inducing in vitro myeloid differentiation in normal and leukemic progenitor cells.1 In vivo, the complete response to RA is typical of promyelocytic leukemia with PML-RARa rearrangement.2 An erratic and incomplete response to RA as been reported in myelodysplastic syndromes3 and in secondary leukemias combining ATRA with low doses of Ara-C.4 We re...

Acute promyelocytic leukemia (APL) is a hematological malignancy driven by a chimeric oncoprotein containing the C terminus of the retinoic acid receptor-a (RARa) fused to an N-terminal partner, most commonly promyelocytic leukemia protein (PML). Mechanistically, PML-RARa acts as a transcriptional repressor of RARa and non-RARa target genes and antagonizes the formation and function of PML nucl...

RETINOIDS AND IN particular retinoic acid are naturally occurring compounds that regulate the growth and differentiation of a variety of different cell types. The observation that retinoic acid induces the terminal differentiation of human acute promyelocytic leukemia (APL) cells both in vitro1 and in vivo2-4 has had a significant impact in clinical hematology and has altered our approach to th...

The transcription factor Stat5 mediates the cellular response to activation of multiple cytokine receptors involved in the regulation of proliferation and differentiation of hematopoietic cells. Recently, the human Stat5 gene was found to be translocated to the RARa gene in a patient with acute promyelocytic leukemia indicating that Stat5 might also play a role in cellular transformation. We in...