ABSTRACT
Introduction 433 Clonal origin of leukemic lymphoid cells 433 Lineage-specific features of leukemic lymphoblasts 433 B cell lymphoblastic lymphoma and acute 434
lymphoblastic leukemia Pre-B and early pre-B acute lymphoblastic leukemia 434 T cell acute lymphoblastic leukemia 434 Genetic basis of lymphoid leukemia 435 Central role of transcriptional control genes 435
Dysregulated expression of structurally intact genes 436 Chimeric transcription factor genes 439 Tyrosine kinase genes: BCR-ABL 443 Tumor suppressor genes 444 Mutated RAS genes 445 Abnormalities of leukemia cell ploidy 445 Future directions 446 Key points 446 References 446
Normal lymphoid cell populations undergo diverse, clonal rearrangements of their IG or TCR genes, followed by highly regulated proliferation of the cells that successfully complete these genetic changes. This developmental process generates B and T cells with the specificities needed to support a fully competent immune system. When a lymphoid progenitor cell becomes genetically altered through somatic changes, the result can be dysregulated proliferation and clonal expansion, eventually leading to acute lymphoblastic leukemia (ALL). In most cases, the pathobiology of transformed lymphoid cells reflects the altered expression of genes whose products contribute to the normal phenotypes of B and T cell progenitors, but it may also involve the aberrant expression of otherwise quiescent genes.
