Novel biological insights in T-cell acute lymphoblastic leukemia

作者：Durinck Kaat; Goossens Steven; Peirs Sofie; Wallaert Annelynn; Van Loocke Wouter; Matthijssens Filip; Pieters Tim; Milani Gloria; Lammens Tim; Rondou Pieter; Van Roy Nadine; De Moerloose Barbara; Benoit Yves; Haigh Jody; Speleman Frank; Poppe Bruce; Van Vlierberghe Pieter

来源：Experimental Hematology, 2015, 43(8): 625-639.

DOI：10.1016/j.exphem.2015.05.017

T-cell acute lymphoblastic leukemia (T-ALL) is 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. Genetic and epigenetic reprogramming events, which transform T-cell precursors into malignant T-ALL lymphoblasts, have been extensively characterized over the past decade. Despite our comprehensive understanding of the genomic landscape of human T-ALL, leukemia patients are still treated by high-dose multiagent chemotherapy, potentially followed by hematopoietic stem cell transplantation. Even with such aggressive treatment regimens, which are often associated with considerable acute and long-term side effects, about 15% of pediatric and 40% of adult T-ALL patients still relapse, owing to acquired therapy resistance, and present with very dismal survival perspectives. Unfortunately, the molecular mechanisms by which residual T-ALL tumor cells survive chemotherapy and act as a reservoir for leukemic progression and hematologic relapse remain poorly understood. Nevertheless, it is expected that enhanced molecular understanding of T-ALL disease biology will ultimately facilitate a targeted therapy driven approach that can reduce chemotherapy-associated toxicities and improve survival of refractory T-ALL patients through personalized salvage therapy. In this review, we summarize recent biological insights into the molecular pathogenesis of T-ALL and speculate how the genetic landscape of T-ALL could trigger the development of novel therapeutic strategies for the treatment of human T-ALL.

• 出版日期2015-8