Novel biological insights in T-cell acute lymphoblastic leukemia

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

Research output: Contribution to journalArticleResearchpeer-review

64 Citations (Scopus)

Abstract

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
Original languageEnglish
Pages (from-to)625-639
Number of pages15
JournalExperimental Hematology
Volume43
Issue number8
DOIs
Publication statusPublished - 2015

Cite this