Genes, Vol. 12, Pages 1118: T-Cell Acute Lymphoblastic Leukemia: Biomarkers and Their Clinical Usefulness

Genes, Vol. 12, Pages 1118: T-Cell Acute Lymphoblastic Leukemia: Biomarkers and Their Clinical Usefulness Genes doi: 10.3390/genes12081118 Authors: Valentina Bardelli Silvia Arniani Valentina Pierini Danika Di Giacomo Tiziana Pierini Paolo Gorello Cristina Mecucci Roberta La Starza T-cell acute lymphoblastic leukemias (T-ALL) are immature lymphoid tumors localizing in the bone marrow, mediastinum, central nervous system, and lymphoid organs. They account for 10–15% of pediatric and about 25% of adult acute lymphoblastic leukemia (ALL) cases. It is a widely heterogeneous disease that is caused by the co-occurrence of multiple genetic abnormalities, which are acquired over time, and once accumulated, lead to full-blown leukemia. Recurrently affected genes deregulate pivotal cell processes, such as cycling (CDKN1B, RB1, TP53), signaling transduction (RAS pathway, IL7R/JAK/STAT, PI3K/AKT), epigenetics (PRC2 members, PHF6), and protein translation (RPL10, CNOT3). A remarkable role is played by NOTCH1 and CDKN2A, as they are altered in more than half of the cases. The activation of the NOTCH1 signaling affects thymocyte specification and development, while CDKN2A haploinsufficiency/inactivation, promotes cell cycle progression. Among recurrently involved oncogenes, a major role is exerted by T-cell-specific transcription factors, whose deregulated expression interferes with normal thymocyte development and causes a stage-specific differentiation arrest. Henc...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Review Source Type: research