NG2 holds a significant position in mediating resistance to glucocorticoids in MLL rearranged B-cell acute lymphoblastic leukaemia (MLLr B-ALL), therefore influencing the success of present therapies. This is the conclusion of a recent study from the European Organization for Research and Treatment of Cancer, which aimed to understand why infants with MLLr B-ALL show resistance to the standard treatment protocol. This finding could facilitate the development of new therapeutic strategies, given that the condition is associated with poor prognosis and frequent relapse.1
Acute lymphoblastic leukaemia is the most prevalent paediatric cancer, with an estimation of 70 to 80 new cases per year in Belgium.2 One of its subtypes, namely MLLr B-ALL, involves rearrangement of the MLL gene and is characterized by a poor prognosis of 5-year survival, frequent relapse and resistance to glucocorticoids.1 However, glucocorticoids are an essential component of the current treatment for MLLr B-ALL, and this has presented an even more significant challenge in clinical settings.
The study published in Blood, journal of the American Society of Hematology, involved a deep analysis of MLLr B-ALL cells from 7 newborns undergoing standard induction therapy. As a result, the transmembrane proteoglycan highly expressed in MLLr B-ALL patients (NG2), was found to interfere with the glucocorticoid receptor NR3C1. This resulted in a weakened glucocorticoid-induced apoptosis. This interference seemed to be responsible for reducing the effectiveness of glucocorticoids, and ultimately contributed to chemoresistance.1
The combination of molecular, genetic, and cellular techniques used by the researchers to explore the role of NG2 in glucocorticoids resistance demonstrated that NG2 knockout (NG2KO) cells were more sensitive to the treatments, leading to a reduction in leukaemic burden compared to NG2 wild-type (NG2WT) cells. Such sensitivity was associated to the downregulation of anti-apoptotic genes in NG2KO cells. A therapeutical combination of glucocorticoids with inhibitors of the PI3K/AKT/mTOR pathways could potentially overcome NG2-mediated resistance.1
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