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Cancers
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NKL Homeobox Genes in Normal and Aberrant Hematopoiesis
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NKL Homeobox Genes in Normal and Aberrant Hematopoiesis

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 10311

Special Issue Editor

Dr. Stefan Nagel

E-Mail Website
Guest Editor
Leibniz-Institute DSMZ, Department of Human and Animal Cell Lines, 38124 Braunschweig, Germany
Interests: homeobox genes; hematopoiesis; leukemia; lymphoma

Special Issue Information

Dear Colleagues, 

Homeobox genes encode conserved transcription factors having major impacts on developmental processes during embryogenesis and in the adult. NKL homeobox genes represent a 48 gene strong subclass of the large ANTP-class of homeobox genes. Well-known members of this subclass encode master factors for the development of the heart (NKX2-5), the prostate (NKX3-1), and of the spleen (NKX3-2 and TLX1), demonstrating the developmental power of these genes. Reflecting their impact on the differentiation of embryonal parts, subgroups of homeobox genes generate specific codes: The HOX-code regulates the anterior–posterior axis, and the DLX-code organizes the pharyngeal region. Accordingly, the recently reported NKL-code describes specific expression patters of 11 NKL homeobox genes in the course of hematopoiesis. NKL master factors for the development of blood cells include HHEX and HLX. Aberrant activities of NKL homeobox genes have been identified in both lymphoid and myeloid malignancies, underlining the oncogenic role of this gene subclass. Deregulated NKL homeobox genes encompass NKL-code members and ectopically expressed non-members. These disturbances of the physiological NKL-code affect differentiation, proliferation, and/or cell survival of hematopoietic progenitors. The knowledge of the functional roles of NKL homeobox genes in normal and malignant hematopoietic cells and tissues may contribute to understand the differentiation processes of blood cells and to design novel therapeutic approaches to treat leukemia and lymphoma. This Special Issue will highlight the dual role of NKL homeobox genes in these settings, reporting examples for genes, cell types, and diseases.

Dr. Stefan Nagel
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • homeobox
  • hematopoiesis
  • lymphopoiesis
  • leukemia
  • lymphoma

Published Papers (2 papers)

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Review

16 pages, 2209 KiB  
Review
DLX Genes: Roles in Development and Cancer
by Yinfei Tan and Joseph R. Testa
Cancers 2021, 13(12), 3005; https://doi.org/10.3390/cancers13123005 - 15 Jun 2021
Cited by 27 | Viewed by 5064
Abstract
Homeobox genes control body patterning and cell-fate decisions during development. The homeobox genes consist of many families, only some of which have been investigated regarding a possible role in tumorigenesis. Dysregulation of HOX family genes have been widely implicated in cancer etiology. DLX [...] Read more.
Homeobox genes control body patterning and cell-fate decisions during development. The homeobox genes consist of many families, only some of which have been investigated regarding a possible role in tumorigenesis. Dysregulation of HOX family genes have been widely implicated in cancer etiology. DLX homeobox genes, which belong to the NK-like family, exert dual roles in development and cancer. The DLX genes are the key transcription factors involved in regulating the development of craniofacial structures in vertebrates. The three DLX bigenes have overlapping expression in the branchial arches. Disruption of DLX function has destructive consequences in organogenesis and is associated with certain congenital disorders in humans. The role of DLX genes in oncogenesis is only beginning to emerge. DLX2 diminishes cellular senescence by regulating p53 function, whereas DLX4 has been associated with metastasis in breast cancer. In human ovarian cancer cells, DLX5 is essential for regulating AKT signaling, thereby promoting cell proliferation and survival. We previously implicated Dlx5 as an oncogene in murine T-cell lymphoma driven by a constitutively active form of Akt2. In this mouse model, overexpression of Dlx5 was caused by a chromosomal rearrangement that juxtaposed the Tcr-beta promoter region near the Dlx5 locus. Moreover, transgenic mice overexpressing Dlx5, specifically in immature T-cells, develop spontaneous thymic lymphomas. Oncogenesis in this mouse model involves binding of Dlx5 to the Notch1 and Notch3 gene loci to activate their transcription. Dlx5 also cooperates with Akt signaling to accelerate lymphomagenesis by activating Wnt signaling. We also discuss the fact that human DLX5 is aberrantly expressed in several human malignancies. Full article
(This article belongs to the Special Issue NKL Homeobox Genes in Normal and Aberrant Hematopoiesis)
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17 pages, 1375 KiB  
Review
NKL-Code in Normal and Aberrant Hematopoiesis
by Stefan Nagel
Cancers 2021, 13(8), 1961; https://doi.org/10.3390/cancers13081961 - 19 Apr 2021
Cited by 15 | Viewed by 4352
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue NKL Homeobox Genes in Normal and Aberrant Hematopoiesis)
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