Relevance of the Hedgehog pathway in T-cell acute lymphoblastic leukemia

T-cell lymphoblastic leukemias (T-ALLs) arise from the malignant transformation of T cell progenitors. The most common genetic alterations include the activation of the NOTCH pathway, deletions within the CDKN2A locus and chromosomal rearrangements affecting T cell-specific enhancer elements. In addition, alterations in other signal transductions pathways and chromatin remodelers translate into the genetic heterogeneity of the disease. T-ALL accounts for 10%–15% of pediatric and 25% of adult cases. Clinical symptoms include hyperleukocytosis with extramedullary involvement of lymph nodes and other organs, including frequent central nervous system infiltration and occurrence of mediastinal masses arising from the thymus. The outcome of T-ALL patients has improved due to intensified chemotherapy protocols and cure rates of 75% in children and 50% in adults can be achieved. But the prognosis of primary resistant or relapsed T-ALL patients remains poor underlining the need for novel targeted therapy strategies (1).