Abstract
Homeobox genes encode transcription factors which control basic processes in development and differentiation. Concerning the sequence conservation in their homeobox, these genes are arranged into particular groups sharing evolutionary ancestry and resembling in function. We have recently described the physiological expression patterns of two homeobox gene groups, NKL and TALE, in early hematopoiesis and subsequent lymphopoiesis. The hematopoietic activities of eleven NKL and nine TALE homeobox genes have been termed as NKL- and TALE-codes, respectively. Due to the developmental impact of homeobox genes, these expression data indicate a key role for their activity in normal hematopoietic differentiation processes, including B-cell development. On the other hand, aberrant expression of NKL- and TALE-code members or ectopic activation of non-code members have been frequently reported in lymphoid malignancies, demonstrating their oncogenic potential in the hematopoietic compartment. Here, we provide an overview of the established NKL- and TALE-codes in normal lymphopoiesis and of deregulated homeobox genes in Hodgkin lymphoma, demonstrating the capability of gene codes to identify homeo-oncogenes in lymphoid malignancies.
Highlights
Due to the developmental impact of homeobox genes, these expression data indicate a key role for their activity in normal hematopoietic differentiation processes, including B-cell development
We provide an overview of the established NKL- and TALE-codes in normal lymphopoiesis and of deregulated homeobox genes in Hodgkin lymphoma, demonstrating the capability of gene codes to identify homeo-oncogenes in lymphoid malignancies
TALE homeobox gene PBX1 is highlighted in blue
Summary
In the course of hematopoiesis, all of the blood and immune cells are produced. Today, developing and mature hematopoietic cells are extensively defined even at the molecular level, allowing for the retracement of underlying mechanisms of cell differentiation [1]. For the final differentiation steps to memory B-cells and plasma cells via the stage of germinal center (GC) B-cells, naïve B-cells migrate into lymph nodes, the spleen, and other lymphoid tissues. In these compartments, additional molecular alterations occur, such as the somatic hypermutation and class switching of the B-cell receptor genes. Several transcription factors (TFs), such as BCL6, EBF1, MYB, PAX5, PRDM1, SPIB, and TCF3 are members of a B-cell specific regulatory network, which orchestrates basic differentiation processes [4,5,6,7]. The knowledge of physiological activities of developmental TFs supports the understanding of both the normal and abnormal processes in B-cell differentiation
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