Blood Journal
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A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlyingPLZF/RARA gene rearrangements

  1. Danielle Sainty,
  2. Vincenzo Liso,
  3. Angelo Cantù-Rajnoldi,
  4. David Head,
  5. Marie-Joëlle Mozziconacci,
  6. Christine Arnoulet,
  7. Laurence Benattar,
  8. Susanna Fenu,
  9. Marco Mancini,
  10. Eliane Duchayne,
  11. François-Xavier Mahon,
  12. Norma Gutierrez,
  13. Françoise Birg,
  14. Andrea Biondi,
  15. David Grimwade,
  16. Marina Lafage-Pochitaloff,
  17. Anne Hagemeijer, and
  18. Georges Flandrin on behalf of Groupe Français d'Hématologie Cellulaire, Groupe Français de Cytogénétique Hématologique, UK Cancer Cytogenetics Group, and BIOMED 1 European Community-Concerted Action “Molecular Cytogenetic Diagnosis in Haematological Malignancies”
  1. 1 From the Institut Paoli-Calmettes, Institut National de la Santé et de la Recherche Médicale (INSERM) U119, IFR 57, and Université de la Méditerranée, Marseille, France; Hôpital Necker Enfants Malades, Paris, France; Laboratoire d'Hématologie, Hôpital Purpan, Toulouse, France; Laboratoire d'Hématologie et d'Immunologie, Hôpital Pellegrin, Bordeaux, France; Cattedra di Ematologica i Policlinico di Bari, Bari, Italy; Dipartimento di Medicina di Laboratorio, Istituti Clinici di Perfezionamento, Milan, Italy; Dipartimento di Biotecnologie Cellulari ed Ematologia, Universita degli Studi “la Sapienza,” Rome, Italy; Centro di Ricerca; M Tettamanti and Ospedale San Gerardo, Monza, Italy; St Jude Children's Hospital, Memphis, TN; the Division of Medical and Molecular Genetics, Guy's, King's and St Thomas' School of Medicine, London, UK; Center for Human Genetics, Leuven, Belgium; and Servicio de Hematologia, Hospital Universitario de Salamanca, Centro de Investigation del Cancer, Universidad de Salamanca, Salamanca, Spain.


Acute promyelocytic leukemia (APL) is typified by the t(15;17) translocation, which leads to the formation of thePML/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/RARAgene 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/RARAcases 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.

  • Submitted December 9, 1999.
  • Accepted April 25, 2000.
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