title: Acute promyelocytic leukemia: from clinic to molecular biology.
abstract: Acute promyelocytic leukemia (APL) is a good model for studying the human malignancies in that up to 90% of APL patients can achieve complete remission (CR) with a differentiation inducer, all-trans retinoic acid (ATRA). 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. Recently the RAR alpha and the PML gene structural alterations in t(15;17) have been characterized. The heterogeneity of the PML rearrangements juxtaposes different PML gene portions to the same set of RAR alpha exons, producing two major PML-RAR alpha fusion mRNA isoforms. A retrotranscriptase/polymerase chain reaction (RT-PCR) analysis of the fusion transcripts has been developed which allows the detection of minimal residual disease during the clinical remission of APL. Molecular study showed PML-RAR alpha can form heterodimers with wild-type PML and RXR. Recently, PML has been shown to be one of the components of a nuclear body, POD. In APL, the normal organization of POD is disrupted by PML-RAR alpha, whereas ATRA treatment in vivo and in vitro can induce a reorganization of this organelle. Cytogenetic and molecular study allowed a variant translocation t(11;17) being recently discovered in a small subset of APL. This time RAR alpha is fused to a new gene, PLZF, on chromosome 11q23. It has been shown that the PLZF-RAR alpha, like PML-RAR alpha, has a "dominant negative" effect on the wild-type RAR-RXR. Clinical data obtained from a group of t(11;17) APL patients showed that these respond poorly to ATRA and could be grouped in a special clinical syndrome within APL. The comparison of the biological activities mediated by PML-RAR alpha and PLZF-RAR alpha may give new insights into the pathogenesis as well as the mechanisms of ATRA-induced differentiation in APL.
authors.affiliation: Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Second Medical University, China.
authors.forename: S J
authors.initials: SJ
authors.lastname: Chen
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
mesh_terms: D002454:Cell Differentiation; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D002880:Chromosomes, Human, Pair 11; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics*; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D018168:Receptors, Retinoic Acid / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic; D014212:Tretinoin / Q000627:therapeutic use*; D025521:Tumor Suppressor Proteins
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D018168:Receptors, Retinoic Acid; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; C092037:ZBTB16 protein, human; D014212:Tretinoin