Clinical implications of recurring chromosomal and associated molecular abnormalities in acute lymphoblastic leukemia.

摘要: Comprehensive study of the major chromosomal/molecular abnormalities in children and adults with acute lymphoblastic leukemia (ALL) has demonstrated prognostic utility for many these anomalies, to extent that cytogenetic molecular genetic evaluations are now required optimal clinical management newly diagnosed cases. For example, t(12;21)/TEL-AML1 (ETV6-CBFA2) or hyperdiploid karyotypes each identifies subgroups who can be cured well-tolerated chemotherapy based primarily on drugs few long-term toxicities, such as L-asparaginase antimetabolites. By contrast, t(1;19)/E2A-PBX1 a subtype ALL responds much better more intensive regimens rely genotoxic drugs. At extreme end risk spectrum, t(4;11)/MLL-AF4 t(9;22)/BCR-ABL almost always confer dire prognosis both ALL, warrant high-dose hematopoietic stem cell rescue sustain even induce first remission. Such markers being incorporated into classification schemes, they convey information cannot gleaned from conventional factors immunophenotype, presenting age, initial circulating leukemic blast count. The most exciting prospect is discovery inhibit specific oncogenes, illustrated by BCR-ABL tyrosine kinase inhibitor STI-571.