Page 296 - 2021_02-Haematologica-web

Letters to the Editor
miR-939 acts as tumor suppressor by modulating JUNB transcriptional activity in pediatric anaplastic large cell lymphoma
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-posi- tive (ALK+) due to the chromosomal translocation t(2;5)(p23;q35), which leads to the constitutive expres- sion and activation of NPM-ALK fusion protein.1 ALK downstream signaling includes multiple oncogenic path- ways and has been directly implicated in ALCL patho- genesis.2 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.3 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.4,5 We recent- ly identified two clearly distinct subgroups of ALCL patients who were characterized by different endoge- nous NPM-ALK expression levels at diagnosis and were defined ALK-high and ALK-low.6 These patients dis- played 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-
C
AB
610
Figure 1. miR-939 is differentially expressed according to anaplastic lymphoma kinase (ALK) expression in tumor tissues. Box plots of differential miR-939 expression in anaplastic large cell lymphoma (ALCL) tumor biopsies detected by (A) human microRNA microarray v.2 (n=16: 11 ALK-high and 5 ALK-low; **P=0.0016) and (B) quantitative reverse transcription PCR (qRT-PCR) (n=49: 39 ALK-high and 10 ALK-low; **P=0.0017). qRT-PCR data have been calculated according to the comparative δCt method, using miR-16 as endogenous control. The horizontal line in the box indicates the median expression level of miR-939 (ALK-low median value: 3.45; ALK-high median value: 2.62). (C) Heterogeneous expression levels of miR-939 in 49 ALCL cases. Data have been measured by qRT-PCR according to the comparative δCt method and compared to reactive lymph nodes tissue (LN, n=11). Blue and red bars are ALK-high and ALK-low tumor biopsies, respectively. miR-939 median expression level=2.83.
haematologica | 2021; 106(2)