TY - JOUR
T1 - A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlying PLZF/RARA gene rearrangements
AU - Sainty, D
AU - Liso, V
AU - Cantu-Rajnoldi, A
AU - Head, D
AU - Mozziconacci, M J
AU - Arnoulet, C
AU - Benattar, L
AU - Fenu, S
AU - Mancini, M
AU - Duchayne, E
AU - Mahon, F X
AU - Gutierrez, N
AU - Birg, F
AU - Biondi, A
AU - Grimwade, D
AU - Lafage-Pochitaloff, M
AU - Hagemeijer, A
AU - Flandrin, G
AU - Groupe Français d'Hématologie Cellulaire
AU - Groupe Français de Cytogénétique Hématologique
AU - UK Cancer Cytogenetics Group
AU - BIOMED 1 European Community-Concerted Action "Molecular Cytogenetic Diagnosis in Haematological Malignancies"
PY - 2000/8/15
Y1 - 2000/8/15
N2 - 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 tacking 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) (C) 2000 by The American Society of Hematology.
AB - 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 tacking 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) (C) 2000 by The American Society of Hematology.
UR - http://www.scopus.com/inward/record.url?scp=0034663180&partnerID=8YFLogxK
M3 - Article
SN - 1528-0020
VL - 96
SP - 1287
EP - 1296
JO - Blood
JF - Blood
IS - 4
ER -