Publication: Novel biological insights in T-cell acute lymphoblastic leukemia

Figure 2. Molecular mechanisms for IL7R/JAK/STAT
activation in T-cell acute lymphoblastic leukemia (T-ALL).

Review article on T-cell acute lymphoblastic leukemia (T-ALL), an aggressive type of blood cancer that accounts for about 15% of pediatric and 25% of adult acute lymphoblastic leukemia (ALL) cases. It is considered as a paradigm for the multistep nature of cancer initiation and progression. T-ALL originates from T-cell precursors at different stages of their development and is characterized by distinct and well characterized molecular genetic subtypes. Children affected by this disease respond fairly well to high-dose chemotherapy regimens. Unfortunately, the clinical response in adults remains problematic, and therapeutic options for relapsed T-ALL patients remain scarce.

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.