Abstract
Simple SummaryGene codes represent expression patterns of closely related genes in particular tissues, organs or body parts. The NKL-code describes the activity of NKL homeobox genes in the hematopoietic system. NKL homeobox genes encode transcription factors controlling basic developmental processes. Therefore, aberrations of this code may contribute to deregulated hematopoiesis including leukemia and lymphoma. Normal and abnormal activities of NKL homeobox genes are described and mechanisms of (de)regulation, function, and diseases exemplified.We have recently described physiological expression patterns of NKL homeobox genes in early hematopoiesis and in subsequent lymphopoiesis and myelopoiesis, including terminally differentiated blood cells. We thereby systematized differential expression patterns of eleven such genes which form the so-called NKL-code. Due to the developmental impact of NKL homeobox genes, these data suggest a key role for their activity in normal hematopoietic differentiation processes. On the other hand, the aberrant overexpression of NKL-code-members or the ectopical activation of non-code members have been frequently reported in lymphoid and myeloid leukemia/lymphoma, revealing the oncogenic potential of these genes in the hematopoietic compartment. Here, I provide an overview of the NKL-code in normal hematopoiesis and instance mechanisms of deregulation and oncogenic functions of selected NKL genes in hematologic cancers. As well as published clinical studies, our conclusions are based on experimental work using hematopoietic cell lines which represent useful models to characterize the role of NKL homeobox genes in specific tumor types.
Highlights
On the other hand, the aberrant overexpression of NKL-code-members or the ectopical activation of non-code members have been frequently reported in lymphoid and myeloid leukemia/lymphoma, revealing the oncogenic potential of these genes in the hematopoietic compartment
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CLPs produce all types of lymphocytes comprising B-cells, T-cells, natural killer (NK)-cells and innate lymphoid cells (ILCs)
Summary
The hematopoietic system comprises all cells derived from hematopoietic stem cells (HSCs) (Figure 1). B-cell development takes place in the bone marrow and begins with the CLP-derived B-cell progenitor (BCP). Intermediate differentiation steps towards mature granulocytes include granulocyte macrophage progenitors (GMPs), early and late pro-myelocytes, and meta-myelocytes. All types of myeloid cells develop within the types of myeloid cells develop within the bone marrow. This diagram depicts theThe progenitors terminallyare differentiated of hematopoiesis, comprising the myeloid (left) and lymphoid (right) lineage. Followingand abbreviations used: BCP: cells of hematopoiesis, comprising the myeloid (left) and lymphoid. TAL1 and LYL1 are basic hehelix-turn-helix TF proteins and regulate vital steps in early and late hematopoiesis [5]. TF proteins and regulate steps in early andstem late cells hematopoiesis [5].
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