LAUSR

Anaplastic large cell lymphoma (ALCL) is a distinct subtype of aggressive non-Hodgkin lymphoma, mainly affecting children and young adults. The vast majority of the pediatric cases are anaplastic lymphoma kinase-positive (ALK) due to the chromosomal translocation t(2;5)(p23;q35), which leads to the constitutive expression and activation of NPM-ALK fusion protein. ALK downstream signaling includes multiple oncogenic pathways and has been directly implicated in ALCL pathogenesis. Current therapeutic approaches can cure 70% of children affected by ALCL. However, despite this, the prognosis of patients experiencing failure of first-line treatment is very poor. The use of biological risk factors such as minimal disseminated disease (MDD), minimal residual disease (MRD), and anti-ALK antibody titer in the forthcoming ALCL trials aims to reduce toxicity for low-risk patients, while making it easier to identify those at higher risk of relapse, who might benefit from more intense regimes and new targeted therapies. We recently identified two clearly distinct subgroups of ALCL patients who were characterized by different endogenous NPM-ALK expression levels at diagnosis and were defined ALK-high and ALK-low. These patients displayed a bimodal distribution for NPM-ALK expression and the median expression values were 2,500 NPM-ALK copies/10,000 ABL1 in ALK-low cases and 125,000 NPM-