Transcription factors and translocations in lymphoid and myeloid leukemia

Abstract

Chromosomal translocations involving transcription factors and aberrant expression of transcription factors are frequently associated with leukemogenesis. Transcription factors are essential in maintaining the regulation of cell growth, development, and differentiation in the hematopoietic system. Alterations in the mechanisms that normally control these functions can lead to hematological malignancies. Further characterization of the molecular biology of leukemia will enhance our ability to develop disease-specific treatment strategies, and to develop effective methods of diagnosis and prognosis. Leukemia (2001) 15, 313-331.

No evidence for core-binding factor CBFβ as a leukemia predisposing factor in chromosome 16q22-linked familial AML

“…1,2 Transcription factors (TFs) play an important role in this process as they frequently show recurrent, somatically acquired, chromosomal abnormalities (translocations and inversions) and point mutations. 2,3 Familial cases of AML are best suited to define the initiating steps in leukemogenesis, and studies of familial AML have identified TF RUNX1 (AML1, CBFA2) as the first known familial leukemia susceptibility gene. 4,5 Core-binding factor CBFb is the cofactor of RUNX1, and both are essential for definitive hematopoiesis and are frequent fusion gene partners in chromosomal translocations in leukemia.…”

The in vivo profile of transcription factors during neutrophil differentiation in human bone marrow

“…2,3 This can be appreciated by recognizing that the differentiation stop associated with acute myeloid leukemia in most cases involves translocations or other mutations that disturb the function of a transcription factor. 4,5 Further documentation comes from experiments involving ectopic expression of transcription factors in myeloid cell cultures 6,7 and targeted disruption of genes encoding transcription factors in mice. [8][9][10][11] Experimental evidence has shown that some transcription factors, such as CCAAT/enhancer binding protein ␣ (C/EBP-␣) and acute myeloid leukemia 1 (AML-1), 8,9 are important during early granulopoiesis whereas others, such as C/EBP-⑀ and CCAAT displacement protein (CDP), 10,12 first exert their function in more mature neutrophil precursors.…”

Development of a Conditional In vivo Model to Evaluate the Efficacy of Small Molecule Inhibitors for the Treatment of Raf-Transformed Hematopoietic Cells

“…Rsk ) or transcription factors [e.g., cyclic AMP-responsive element binding protein (CREB), Elk, and c-Myc] which enter the nucleus and regulate gene expression (19,20). NH 2 -terminal deleted forms of Raf and MEK1 proteins, which remove the Ras binding domain and the negative regulatory sites in CR1 and CR2 in Raf and the negative regulatory domain of MEK1, result in activated oncoproteins due to the aberrant stimulation of downstream kinases, transcription factors, and molecules involved in the prevention of apoptosis (17,18,21).…”