In hematopoietic cell development, the transcriptional program is strictly 
regulated in a lineage- and stage-specific manner that requires a number of 
transcription factors to work in a cascade or in a loop, in addition to 
interactions with nonhematopoietic cells in the microenvironment. Disruption of 
the transcriptional program alters the cellular state and may predispose cells 
to the acquisition of genetic abnormalities. Early studies have shown that 
proteins that promote cell differentiation often serve as tumor suppressors, 
whereas inhibitors of those proteins act as oncogenes in the context of acute 
leukemia. A prime example is T-cell acute lymphoblastic leukemia (T-ALL), a 
malignant disorder characterized by clonal proliferation of immature stage 
thymocytes. Although a relatively small number of genetic abnormalities are 
observed in T-ALL, these abnormalities are crucial for leukemogenesis. Many 
oncogenes and tumor suppressors in T-ALL are transcription factors that are 
required for normal hematopoiesis. The transformation process in T-ALL is 
efficient and orchestrated; the oncogene disrupts the transcriptional program 
directing T-cell differentiation and also uses its native ability as a master 
transcription factor in hematopoiesis. This imbalance in the transcriptional 
program is a primary determinant underlying the molecular pathogenesis of T-ALL. 
In this review, we focus on the oncogenic transcription factor TAL1 and the 
tumor-suppressor E-proteins and discuss the malignant cell state, the 
transcriptional circuit, and the consequence of molecular abnormalities in 
T-ALL.