TY - JOUR
T1 - Novel biological insights in T-cell acute lymphoblastic leukemia
AU - Durinck, Kaat
AU - Goossens, Steven
AU - Peirs, Sofie
AU - Wallaert, Annelynn
AU - Loocke, Wouter Van
AU - Matthijssens, Filip
AU - Pieters, Tim
AU - Milani, Gloria
AU - Lammens, Tim
AU - Rondou, Pieter
AU - Roy, Nadine Van
AU - Moerloose, Barbara De
AU - Benoit, Yves
AU - Haigh, Jody
AU - Speleman, Frank P
AU - Poppe, Bruce
AU - Van Vlierberghe, Pieter
PY - 2015
Y1 - 2015
N2 - 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
AB - 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
UR - http://www.sciencedirect.com/science/article/pii/S0301472X15002118
U2 - 10.1016/j.exphem.2015.05.017
DO - 10.1016/j.exphem.2015.05.017
M3 - Article
SN - 0301-472X
VL - 43
SP - 625
EP - 639
JO - Experimental Hematology
JF - Experimental Hematology
IS - 8
ER -