Molecular-genetic insights in paediatric T-cell acute lymphoblastic leukaemia.
Paediatric T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive malignancy of thymocytes that accounts for about 15% of ALL cases and for which treatment outcome remains inferior compared to B-lineage acute leukaemias. In T-ALL, leukemic transformation of maturating thymocytes is caused by a multistep pathogenesis involving numerous genetic abnormalities that drive normal T-cells into uncontrolled cell growth and clonal expansion. This review provides an overview of the current knowledge on onco- and tumor suppressor genes in T-ALL and suggests a classification of these genetic defects into type A and type B abnormalities. Type A abnormalities may delineate distinct molecular-cytogenetic T-ALL subgroups, whereas type B abnormalities are found in all major T-ALL subgroups and synergize with these type A mutations during T-cell pathogenesis.
Van Vlierberghe
Pieter
P
Department of Paediatric Oncology/Haematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.
Pieters
Rob
R
Beverloo
H Berna
HB
Meijerink
Jules P P
JP
D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002648:Child; D015329:Gene Rearrangement, T-Lymphocyte; D005801:Genes, Homeobox; D006801:Humans; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000235:genetics*; D011519:Proto-Oncogenes; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
D011948:Receptors, Antigen, T-Cell