The biology of pediatric acute megakaryoblastic leukemia
Cet article passe en revue les travaux récents sur les caractéristiques biologiques d'une leucémie aiguë mégacaryoblastique
Acute Megakaryoblastic Leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) that morphologically resembles abnormal megakaryoblasts. While extremely rare in adults, pediatric cases comprise between 4 and 15% of newly diagnosed AML patients. AMKL in children with Down syndrome (DS) is characterized by a founding GATA1 mutation that cooperates with trisomy 21, followed by the acquisition of additional somatic mutations in epigenetic and kinase signaling genes. Clinically this manifests as a transient myeloproliferative disease (TMD) in the first year of life, followed by spontaneous resolution and the subsequent development into AMKL in a small fraction of patients with a latency of one to five years. Outcomes in DS-AMKL are excellent, with greater than 80% overall survival. In contrast, non-DS-AMKL is predominantly characterized by recurrent chimeric oncogenes comprised of genes known to play a role in normal hematopoiesis. These patients present acutely, ranging in age from infancy to adolescence. CBFA2T3-GLIS2 is the most frequent chimeric oncogene identified to date in this subset of patients, and carries an inferior event free and overall survival in contrast to non-DS-AMKL cases that lack this fusion protein. Thus efforts to target this oncogene will be important to improve outcomes.
Blood , résumé, 2014