title: A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlying PLZF/RARA gene rearrangements.
abstract: Acute promyelocytic leukemia (APL) is typified by the t(15;17) translocation, which leads to the formation of the PML/RARA fusion gene and predicts a beneficial response to retinoids. However, approximately 10% of all APL cases lack the classic t(15;17). This group includes (1) cases with cryptic PML/RARA gene rearrangements and t(5;17) that leads to the NPM/RARA fusion gene, which are retinoid-responsive, and (2) cases with t(11;17)(q23;q21) that are associated with the PLZF/RARA fusion gene, which are retinoid-resistant. A key issue is how to rapidly distinguish subtypes of APL that demand distinct treatment approaches. To address this issue, a European workshop was held in Monza, Italy, during June 1997, and a morphologic, immunophenotypic, cytogenetic, and molecular review was undertaken in 60 cases of APL lacking t(15;17). This process led to the development of a novel morphologic classification system that takes into account the major nuclear and cytoplasmic features of APL. There were no major differences observed in morphology or immunophenotype between cases with the classic t(15;17) and those with the cryptic PML/RARA gene rearrangements. Auer rods were absent in the t(5;17) case expressing NPM/RARA. Interestingly, this classification system distinguished 9 cases with t(11;17)(q23;q21) and, in addition, successfully identified 2 cases lacking t(11;17), which were subsequently shown to have underlying PLZF/RARA fusions. The PLZF/RARA cases were characterized by a predominance of blasts with regular nuclei, an increased number of Pelger-like cells, and by expression of CD56 in 4 of 6 cases tested. Use of this classification system, combined with an analysis for CD56 expression, should allow early recognition of APL cases requiring tailored molecular investigations. (Blood. 2000;96:1287-1296)
authors.affiliation: Department of Biology, Institut Paoli-Calmettes, Marseille, France. saintyd@marseille.fnclcc.fr
authors.forename: D
authors.initials: D
authors.lastname: Sainty
authors.forename: V
authors.initials: V
authors.lastname: Liso
authors.forename: A
authors.initials: A
authors.lastname: Cantù-Rajnoldi
authors.forename: D
authors.initials: D
authors.lastname: Head
authors.forename: M J
authors.initials: MJ
authors.lastname: Mozziconacci
authors.forename: C
authors.initials: C
authors.lastname: Arnoulet
authors.forename: L
authors.initials: L
authors.lastname: Benattar
authors.forename: S
authors.initials: S
authors.lastname: Fenu
authors.forename: M
authors.initials: M
authors.lastname: Mancini
authors.forename: E
authors.initials: E
authors.lastname: Duchayne
authors.forename: F X
authors.initials: FX
authors.lastname: Mahon
authors.forename: N
authors.initials: N
authors.lastname: Gutierrez
authors.forename: F
authors.initials: F
authors.lastname: Birg
authors.forename: A
authors.initials: A
authors.lastname: Biondi
authors.forename: D
authors.initials: D
authors.lastname: Grimwade
authors.forename: M
authors.initials: M
authors.lastname: Lafage-Pochitaloff
authors.forename: A
authors.initials: A
authors.lastname: Hagemeijer
authors.forename: G
authors.initials: G
authors.lastname: Flandrin
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D015473:Leukemia, Promyelocytic, Acute / Q000145:classification* / Q000235:genetics / Q000473:pathology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D018168:Receptors, Retinoic Acid / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D015514:Oncogene Proteins, Fusion; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; C092037:ZBTB16 protein, human