Identification of homeobox-containing genes expressed in hematopoietic blast cells

Vieille-Grosjean, Isabelle; Roullot, Valérie; Courtois, Gilles

doi:10.1016/0006-291x(92)91694-l

Cited by 21 publications

(9 citation statements)

References 16 publications

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“…Furthermore, the HOXC genes in lymphoid cells of normal or malignant HP1 gene appears to be highly active in the CD34 0 tissues (35, 43 -46). HOXC4 is expressed at high levels subset of cells in which HOX genes are downregulated, in tonsillar B lymphocytes and in B-CLL (38). Further-which is consistent with the role of PG proteins as negamore, HOXC4 transcripts are present in peripheral tive regulators of HOX genes.…”

supporting

confidence: 52%

Effects ofHOX homeobox genes in blood cell differentiation

Magli¹,

1997

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The burgeoning number of articles concerning the role of HOX genes and hematopoiesis ensures that this will continue to be an area of very active research. It seems clear that HOX genes are expressed in stage- and lineage-specific patterns during early stages of hematopoietic development and differentiation. Several lines of evidence suggest that multiple genes of the HOXB (B2, B4, B6-B9), HOXC (C6, C8), and HOXA (A5) are involved in erythropoiesis. Similarly, a number of genes of the HOXA, HOXB, and HOXC appear to play a role in lymphoid cells. Furthermore, several genes, such as A9, A10, B3, B7, and B8, may control myelomonocytic differentiation. The question arises as to whether such a multiplicity of HOX genes reflects redundancy or indicates subtlety of the regulatory machinary. A similar complexity has been observed for hematopoietic cytokines, and the current view is that, although multiple molecules may have similar or overlapping effects, each factor has a specific function and regulatory combinations appear to play a critical role in controlling hematopoietic cell processes (99). One challenge for the future is to delineate in more detail the precise expression patterns of these genes in the many distinct subpopulations of blood cells and during fetal development. Overexpression of HOX genes in hematopoietic cells can dramatically perturb the differentiation of various cell lineages and can contribute to leukemogenesis. Future studies may involve the overexpression of alternatively spliced versions of different HOX genes or of truncated versions of HOX genes to ascertain the functional domains of the proteins that mediate the biologic effects. The findings in HOX knockout mice confirm a role for these genes in normal blood cell development. Further work in this area will require careful examination of fetal hematopoiesis and of animals bearing multiple HOX gene knockouts. Involvement of HOX genes in leukemia is just beginning to be appreciated. Establishing the true extent of HOX gene mutations in human disease will require strategies such as comparative genomic hybridization (100) and analysis of high density oligonucleotide arrays (101). The holy grail of homeobox work is to discover the physiologic processes and specific target genes regulated by HOX proteins. Given the broad range of tissues in which HOX genes are expressed, they would appear to be involved in very basic cellular processes, e.g., cell proliferation and death, adhesion, and migration, etc., rather than the direct regulation of tissue-specific genes. The search for target genes may be made easier by the further characterization of cooperative DNA binding between HOX proteins and other transcription factors. We speculate that HOX proteins do not behave as conventional transcriptional activators or inhibitors but rather may mark genes for potential future activation, i.e., they may establish competency to execute specific differentiation programs, with the actual activation being accomplished by transcriptional pathways triggered by exo...

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supporting

confidence: 52%

Effects ofHOX homeobox genes in blood cell differentiation

Magli¹,

1997

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“…No expression of the HOXD cluster genes was found. [170][171][172][173] Not only the number of HOXA genes, but also the expression level of these genes was higher than that of HOXB genes in enriched CD34 + subpopulations, including the self-renewing stem cell. 172 In addition, it appeared from two studies that HOX genes are colinearly expressed during differentiation of myeloid and erythroid cells.…”

Section: Hox Gene Expression In Normal Hematopoietic Bone Marrow Cellsmentioning

confidence: 99%

The role of Homeobox genes in normal hematopoiesis and hematological malignancies

et al. 1999

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In the last decade it has become clear that homeobox containing genes (HOX genes) not only play a significant role in regulating body formation, but in addition, they are contributing to organization and regulation of hematopoiesis. Modern molecular technologies showed that deregulated expression or disruption of Hox genes can lead to altered characteristics of blood cells or disturbance of blood cell development. In this paper we review the role of HOX proteins in hematopoiesis and leukemogenesis and speculate about their possible target genes and involvement in lymphomagenesis.

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“…The amplified total cDNA derived from each different bone marrow subpopulation or cell line was subjected to a second round of PCR amplification using degenerate primer sets designed to match all of the different sequences represented at the conserved a-1 helix [5'-(TC)(TCGA)GA(AG)(TC)T(CG)-GA(AG)AA(AG)GA-(AG)TT-3'] and the a-3 helix (5'-C (GT)(ACGT)C(GT)(AG)TTCTG(AG)AACCA(ACGT)A-3'] regions of the human Hox gene homeodomains (8). One percent of the total cDNA (0.5 /l) of each subpopulation was amplified and the resulting 118-bp products were subcloned and sequenced.…”

Section: Methodsmentioning

confidence: 99%

Differential expression of homeobox genes in functionally distinct CD34+ subpopulations of human bone marrow cells.

Sauvageau

Lansdorp

Eaves

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

477

423

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Class I homeobox (Hox) genes encode a major group of transcription factors controlling embryonic development and have been implicated in the continuing process of hematopoietic cell differentiation. They are clustered on four chromosomes and, in early development, exhibit spatially restricted expression with respect to their 3'-> 5' chromosomal position. By using an improved PCR-based method for amplifying total cDNA derived from limited cell numbers, we now describe the expression of class I Hox genes in highly purified CD34+ cell subpopulations isolated from normal human bone marrow that represent functionally distinct stem and progenitor cell compartments. Our data indicate that at least 16 different Hox genes, mainly from the A and the B clisters, are expressed in one or more of these subpopulations of human hematopoietic cells. Moreover, markedly elevated expression of some of the Hox genes found at the 3' end of the A and B clusters (e.g., HoxB3) was a unique feature of the subpopulations that contained the most primitive functionally defined cells, whereas genes located in the S' region of each cluster (e.g., HoxA10) were found to be expressed at nearly equal levels in the CD34+ subpopulations analyzed. In contrast to the findings for CD34+ cells, expression of two selected Hox genes, HoxB3 and HoxA10, was virtually extinguished in the CD34-fraction of bone marrow cells. These results demonstrate the expression of a broad range of Hox genes in primitive hematopoietic cells and point to the existence of a regulated program of Hox gene expression during their normal development.

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Identification of homeobox-containing genes expressed in hematopoietic blast cells

Cited by 21 publications

References 16 publications

Effects ofHOX homeobox genes in blood cell differentiation

Effects ofHOX homeobox genes in blood cell differentiation

The role of Homeobox genes in normal hematopoiesis and hematological malignancies

Differential expression of homeobox genes in functionally distinct CD34+ subpopulations of human bone marrow cells.

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