فارسی
PML-RAR is a unique subtype of acute myeloid leukemia (AML) called acute promyelocytic leukemia (APL). In this disease, promyelocytic cells (immature white blood cells) are overproduced and accumulate in the bone marrow. APL is caused by a genetic fusion between two genes, PML and RAR, forming a fusion gene called PML-RAR. Translocation (chromosomal displacement) between the q22 region of chromosome 15 and the q21 region of chromosome 17 leads to the formation of the PML-RAR fusion gene sequence.
Typically, the PML gene encodes a protein that helps prevent uncontrolled cell growth and acts as a tumor suppressor. The RAR Alpha (RARA) gene is also a member of the nuclear hormone receptor gene family that is essential for regulating some important biological processes in the body. This gene encodes a DNA-bound finger protein that is associated with several other proteins in a macromolecular complex and forms separate nuclear bodies. This interesting protein appears to play a role in multiple cellular functions, including regulation of transcription, apoptosis, cell growth and differentiation, immune system regulation, and regulation of metabolism and evolution-related genes.
Additionally, the RARA protein product is essential for the maturation of white blood cells (WBC). The product of the RARA gene is a subunit of a heterodimeric nuclear receptor for the natural ligand retinoic acid or vitamin A. The retinoid nuclear receptor pathway operates in many aspects of normal cell proliferation and differentiation. However, the mutated PML-RARA fusion gene encodes an abnormal fusion protein that does not perform any of these functions but instead leads to the production and accumulation of uncontrolled leukemic white blood cells that do not mature beyond the promyelocytic stage. Since a large number of these abnormal cells begin to destroy natural cellular precursors in the bone marrow, signs and symptoms of leukemia begin to appear.
Up to 98% of cases of acute promyelocytic leukemia (APL) have a reciprocal chromosomal translocation (15,17)t involving the PML-RARA fusion gene. In about 2% of APL cases, other translocations involving the RARA gene and genes other than PML have been reported.
The PML-RAR diagnostic test detects RNA copies made by the cell from the abnormal DNA gene sequence of the PML-RARA fusion gene or its transcripts. The presence of PML-RARA abnormality helps confirm the diagnosis of APL. This test can also guide APL treatment and monitor at least the remaining disease, which can be fatal. APL treatment usually involves all-trans retinoic acid (ATRA) (a drug that binds to retinoic acid receptors on cells). This drug can overcome the effects of the abnormal PML-RARA protein and induce signaling downstream and maturation of WBCs. This treatment method works well with chemotherapy but is only effective in cases where the PML-RARA fusion gene is present. The PML-RAR diagnostic test is performed qualitatively and quantitatively.
