| Description | 560 amino acids, 70 KDa (longest isoform); composed successively, from the N- to the C-terminus, by: 1- a proline-rich N-terminus 2- a so-called "tripartite motif", cysteine-histidine rich, composed of a RING finger structure and 2 B box domains, with putative DNA-binding function 3- a coiled-coil motif corresponding to a dimerization interface 4- a basic sequence with a nuclear localization domain, and 5- a serine-proline rich C-terminal region, of unknown function, variable in length (alternative splicing) and containing phosphorylation sites |
| Expression | in a wide variety of tissues. In hematopoietic tissue, expression apparently restricted to myeloid precursors |
| Localisation | nuclear, as part of a multiproteic complex located into multiple subnuclear PML oncogenic domains (PODs) |
| Function | unknown to date; putative transcription factor; in conjunction with other proteins included in the PODs, it would play a role as tumor suppressor and in apoptosis |
| Homology | with (numerous) other RING finger / B box proteins |
| Entity | t(15;17)(q22;q21) / acute promyelocytic leukemia (APL) -->PML- RARA |
| Disease | typical APL (or M3 ANLL, FAB classification), approximately 98% of APL cases; abnormal promyelocytes with Auer rods and bundles (faggots); disruption of the PODs with a microspeckeled pattern; maturation response to all-trans retinoic acid (ATRA) therapy |
| Prognosis | immediate prognosis impaired by intravascular disseminated coagulopathy; long term prognosis is favorable with treatment combining ATRA plus chemotherapy |
| Cytogenetics | variant or complex t(15;17) translocation in 5% of cases, no known prognosis implication; secondary chromosomal abnormalities in 30 to 35% of APL at diagnosis; association with +8 in 17 to 28% of cases; other associations are rare but recurrent: del(7q), del(9q), ider(17)t(15;17), +21 |
| Hybrid/Mutated Gene | the crucial fusion transcript is 5'PML-3'RARA, encoded by der(15) chromosome; the counterpart 5'RARA-3'PML encoded by der(17) is inconstant breakpoint in RARA gene is always located in intron between A and B domains three breakpoint clusters in PML gene: bcr1 (70% of patients), bcr2 (10%) and bcr3 (20%), giving rise respectively to the long (L), intermediate (V) and short (S) length hybrid PML-RARAtranscripts; V form would be linked to ATRA decreased sensitivity and S form to association with an excess of secondary chromosome changes. |
| Abnormal Protein | 106 Kda fusion protein; role in the leukemogenic process by probable interference with the signalling pathway leading to differentiation and maturation of myeloid precursors (mainly dysregulation of retinoid-inducible genes involved in myeloid differentiation) |
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