APL is a model for oncogene-targeted therapies: <i>all-trans</i> retinoic acid (ATRA) and arsenic both target and degrade its ProMyelocytic Leukemia/Retinoic Acid Receptor α (PML/RARA) driver.
The t(15;17) translocation generates a PML-RARα fusion protein causative for acute promyelocytic leukemia (APL).Li et al. now identify the pseudokinase stress protein TRIB3 as an important factor in APL disease progression and therapy resistance.
APL is characterized by a balanced reciprocal chromosomal translocation fusing the promyelocytic leukaemia (PML) gene on chromosome 15 with the retinoic acid receptor α (RARα) gene on chromosome 17.
APL cell treatment with all-trans-retinoic acid (RA) degrades the chimeric, dominant-negative-acting transcription factor promyelocytic leukemia gene (PML)/RARα, which is generated in APL by chromosomal translocation.
APL is associated with a reciprocal chromosomal translocation of chromosomes 15 and 17, which results in a fusion protein comprising PML and the retinoic acid receptor alpha.
APL is characterized by three distinct and unique features: i) accumulation in the bone marrow of tumor cells with promyelocytic features; ii) invariable association with specific translocations which always involve chromosome 17 and the retinoic acid receptor alpha (RAR alpha) locus; iii) exquisite sensitivity of APL blasts to the differentiating action of retinoic acid (RA).
These data, along with previous reports of rare variant translocations in APL, indicate that while dysregulation of RARA by gene fusion may be essential for the APL phenotype, the particular fusion partner may determine clinicopathological aspects, including presentation, response to treatment with all-trans retinoic acid (ATRA), and prognosis.
APL is characterized cytogenetically by a t(15;17) translocation which involves both the PML gene on chromosome 15 and the RARa gene on chromosome 17 and gives rise to the PML/RARa fusion protein.
APL is characterized cytogenetically by a t(15;17) translocation which involves both the PML gene on chromosome 15 and the RAR alpha gene on chromosome 17 and gives rise to the PML/RAR alpha fusion protein.
APL associated with t(11;17) and fusion of the PLZF and RAR alpha genes is a discrete clinico-pathologic syndrome with a distinctly worse prognosis than t(15;17) APL.
APL is also associated with a specific chromosomal translocation t(15;17) which fuses the retinoic acid receptor alpha (RAR alpha) gene with a chromosome 15q locus, PML.
APL is associated with a reciprocal chromosomal translocation t(15,17) which has been shown to disrupt the retinoic acid receptor alpha (RAR alpha) gene.