Haematologica
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Published online 6 October 2008
Haematologica, Vol 93, Issue 12, 1899-1902 doi:10.3324/haematol.13035
Copyright © 2008 by Ferrata Storti Foundation
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Acute Myeloid Leukemia

Blocking the APRIL circuit enhances acute myeloid leukemia cell chemosensitivity

Désirée Bonci1, Maria Musumeci1, Valeria Coppola1, Antonio Addario1, Concetta Conticello2, Michael Hahne3, Massimo Gulisano4, Francesco Grignani5, Ruggero De Maria1,2

1 Dept. of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome, Italy
2 Mediterranean Institute of Oncology, Catania, Italy
3 Institut de Génétique Moléculaire de Montpellier, France
4 IOM Ricerca, Catania, Italy
5 Patologia Generale, Dipartimento di Medicina Clinica e Sperimentale, Perugia University, Policlinico Monteluce, Perugia, Italy

Correspondence: Ruggero De Maria, MD, Chairman, Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 0161, Rome, Italy. E-mal:demaria{at}iss.it

Resistance to chemotherapy-induced cell death represents a major obstacle in the treatment of acute myeloid leukemia. APRIL (A Proliferation Inducing Ligand) is a member of the tumor necrosis factor superfamily that plays a key role in normal B-cell development, while promoting survival and proliferation of malignant B cells. We investigated APRIL expression and activity in acute myeloid leukemia. We found that APRIL mRNA and protein, including the secreted form, are expressed in leukemic cells of patients with M0, M2 and M4 acute myeloid leukemia subtypes but not in normal hematopoietic progenitors. Retrovirus-mediated APRIL expression in normal hematopoietic progenitors confers resistance to chemotherapeutic drugs-induced apoptosis. Conversely, blocking APRIL function by recombinant soluble APRIL receptors increased chemotherapeutic drugs-induced cell adeath in acute myeloid leukemia cells. These results indicate that APRIL acts in an autocrine fashion to protect acute myeloid leukemia cells from drug-induced death and foresee a therapeutic potential of APRIL antagonists in the treatment of acute myeloid leukemia.

Key words: acute myeloid leukemia, APRIL, chemosensitivity.






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