Abstract
Homeobox genes encode transcription factors controlling basic developmental processes. The homeodomain is encoded by the homeobox and mediates sequence-specific DNA binding and interaction with cofactors, thus operating as a basic regulatory platform. Similarities in their homeobox sequences serve to arrange these genes in classes and subclasses, including NKL homeobox genes. In accordance with their normal functions, deregulated homeobox genes contribute to carcinogenesis along with hematopoietic malignancies. We have recently described the physiological expression of eleven NKL homeobox genes in the course of hematopoiesis and termed this gene expression pattern NKL-code. Due to the developmental impact of NKL homeobox genes these data suggest a key role for their activity in the normal regulation of hematopoietic cell differentiation including T-cells. On the other hand, aberrant overexpression of NKL-code members or ectopical activation of non-code members has been frequently reported in lymphoid and myeloid leukemia/lymphoma, demonstrating their oncogenic impact in the hematopoietic compartment. Here, we provide an overview of the NKL-code in normal hematopoiesis and discuss the oncogenic role of deregulated NKL homeobox genes in T-cell malignancies.
Highlights
The homeodomain is encoded by the homeobox and mediates sequence-specific DNA binding and interaction with cofactors, operating as a basic regulatory platform
All blood and immune cells are classified as lymphoid or myeloid and generated by hematopoietic stem cells (HSC) which reside in the bone marrow
Ferrando and coworkers described the aberrant expression of NKL homeobox gene TLX1 at the double positive (DP) stage in T-cell acute lymphoid leukemia (TALL), indicating that this gene promotes developmental arrest of malignant thymocytes [4]
Summary
Homeobox genes encode one of the largest groups of TFs in the human genome [5]. They regulate basic development and differentiation in both embryogenesis and adulthood. These genes share the conserved homeobox which is 180 bp long and encodes the homeodomain at Biomedicines 2021, 9, 1676. 60 amino homeobox acid residues which three helices, homeodomain at the protein level This domain consists of 60 amino acid residues wh generating a specific 3D structure of the helix-turn-helix type. Machinery including corepressors of the TLE family and specific DNA sequences, respectively
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