|Figure 2. Molecular mechanisms for IL7R/JAK/STAT |
activation in T-cell acute lymphoblastic leukemia (T-ALL).
Notably, the high survival rates reported in pediatric T-ALL protocols could result from overtreatment of a significant fraction of children. Therefore, and given the long-term side effects associated with intensive chemotherapy, risk stratification in future pediatric T-ALL treatment protocols should be further optimized based on our enhanced understanding of T-ALL disease biology. On the other hand, further reduction of chemotherapy can also be achieved by translation of our molecular genetic findings into novel targeted therapies for the treatment of human T-ALL. In that context, a variety of preclinical studies have reported promising therapeutic effects for particular small-molecule inhibitors targeting specific oncogenic pathways (Table 1). Hopefully, some of these novel therapeutic strategies can be implemented in daily clinical practice in complement with low-dose chemotherapy. This will require an accurate definition of the specific T-ALL patient population that might benefit from these novel targeted therapies.
Reference: Durinck, K, Goossens, S, Peirs, S, Wallaert, A, Van Loocke, W, Matthijssens, F, Pieters, Milani, G, Lammens, Rondou, P, Van Roy, N, De Moerloose, B, Benoit, Y, Haigh, J, Speleman, F, Poppe, B, Van Vlierberghe, P. Novel biological insights in T-cell acute lymphoblastic leukemia. Exp Hematol. 2015 Aug;43(8):625-39. doi: 10.1016/j.exphem.2015.05.017. Epub 2015 Jun 26.