Regulation of vertebrate homeobox‐containing genes by morphogens

Mavilio, Fulvio

doi:10.1111/j.1432-1033.1993.tb17660.x

Cited by 75 publications

(50 citation statements)

References 181 publications

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“…3 Homeogenes, originally described in Drosophila melanogaster, are organized in gene clusters evolutionarly conserved. 4,5 In humans the homeobox genes are arranged in four gene clusters, named A, B, C and D, mapped on chromosomes 7, 17, 12 and 2, respectively. 6 Many of the HOX genes have been implicated in the regulation of both normal and leukemic hematopoiesis (reviewed in Refs 7-10).…”

Section: Introductionmentioning

confidence: 99%

Expression pattern of HOXB6 homeobox gene in myelomonocytic differentiation and acute myeloid leukemia

et al. 2002

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Homeobox genes encode transcription factors known to be important morphogenic regulators during embryonic development. An increasing body of work implies a role for homeobox genes in both hematopoiesis and leukemogenesis. In the present study we have analyzed the role of the homeobox gene, HOXB6, in the program of differentiation of the myeloid cell lines, NB4 and HL60. HOXB6 expression is transiently induced during normal granulocytopoiesis and monocytopoiesis, with an initial induction during the early phases of differentiation, followed by a blockade of expression at early maturation. The enforced expression of HOXB6 in promyelocytic NB4 cells or in myeloblastic HL60 cells elicited inhibition of the granulocytic or monocytic maturation, respectively. Furthermore, HOXB6 was frequently expressed (18 out of 49 cases) in AMLs lacking major translocations while it was expressed at very low frequency (two out of 47 cases) in AMLs characterized by PML/RAR-␣, AML-1/ETO, CBF␤/MYH11 fusion and rearrangements of the MLL gene at 11q23. According to these observations, we suggest that a regulated pattern of HOXB6 expression is required for normal granulopoiesis and monocytopoiesis. Abnormalities of the HOXB6 expression may contribute to the development of the leukemic phenotype.

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Section: Introductionmentioning

confidence: 99%

Expression pattern of HOXB6 homeobox gene in myelomonocytic differentiation and acute myeloid leukemia

et al. 2002

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“…Products of homeobox (HOX) genes are transcription factors that control cellular proliferation/di erentiation during development (Krumlauf, 1994;Mavilio, 1993) and are necessary for proliferation of normal adult hematopoietic precursors (Giampaolo et al, 1994;Sauvageau et al, 1994), NK cells (Quaranta et al, 1996) and T lymphocytes (CareÁ et al, 1994). The coordinate expression of HOX genes as described in teratocarcinoma (Mavilio 1993), activated T lymphocytes (CareÁ et al, 1994) and progenitor hematopoietic cells (Giampaolo et al, 1994;Sauvageau et al, 1994) appears to be lost in neoplasias of di erent origin (CareÁ et al, 1996;Cillo et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

“…The coordinate expression of HOX genes as described in teratocarcinoma (Mavilio 1993), activated T lymphocytes (CareÁ et al, 1994) and progenitor hematopoietic cells (Giampaolo et al, 1994;Sauvageau et al, 1994) appears to be lost in neoplasias of di erent origin (CareÁ et al, 1996;Cillo et al, 1992). The oncogenic potential of several murine Hox genes has been demonstrated by in vitro and in vivo transformation assays (Maulbecker and Gruss, 1993), while divergent human and murine homeobox containing genes such as Pbx1, tcl-3, HB24 and meisl are involved in speci®c chromosomal translocations (Dedera et al, 1993;Hatano et al, 1991) or are associated with di erent leukemias (Deguchi et al, 1993;Moskow et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Transduction of the SkBr3 breast carcinoma cell line with the HOXB7 gene induces bFGF expression, increases cell proliferation and reduces growth factor dependence

et al. 1998

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Several melanomas, carcinomas, glioblastomas and leukemias showed coordinated expression of HOXB7 and bFGF with exception of the SkBr3 mammary carcinoma that was negative for both. Transduction of HOXB7 gene into SkBr3 cells, induced bFGF expression, increased growth rate, independence from serum withdrawal and ability to form colonies in semisolid medium. ELISA assay showed that most of bFGF was associated to cell lysate when cells were cultured at 1% serum whereas in cells kept to 10% serum bFGF was detected both within cell lysate or secreted into cell supernatants. Antisense oligos to bFGF inhibited the growth of cells cultured in 1%, indicating that beside the possible activation of additional genes other than bFGF by HOXB7 transduction, only bFGF induction accounts for the observed results. Moreover, since inhibition of cell proliferation occurred in cells kept in 1% but not 10% serum, a bFGF intracrine loop appears operative in serum starved SkBr3/HOXB7 cells. Also, these results further indicate bFGF as target of HOXB7.

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“…Homeogenes, originally identi®ed in Drosophila malanogaster, are organized in multigene clusters highly conserved in all analysed species (Deschamps and Meijlink, 1992;Mavilio, 1993). In the human genome four clusters, named A, B, C and D, have been mapped on chromosomes 7, 17, 12 and 2 respectively (Scott, 1992).…”

Section: Introductionmentioning

confidence: 99%

Enforced expression of HOXB7 promotes hematopoietic stem cell proliferation and myeloid-restricted progenitor differentiation

et al. 1999

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Hematopoietic progenitor/stem cells (HPCs/HSCs) puri®ed from human adult peripheral blood (PB) were triggered into cycling, retrovirally transduced with HOXB7 and then functionally assayed in vitro. HPCs were assayed in multi-and unilineage di erentiation cultures in either liquid phase or semisolid medium, primitive HPCs in the high proliferative potential colony-forming cell (HPP ± CFC) evaluation system and putative HSCs in Dexter type long-term culture (LTC) as LTC initiating cells (LTC ± ICs). Control experiments ensured that the exogenous HOXB7 gene was constantly expressed, while the endogenous one was barely or not transcribed. Enforced expression of the gene markedly modulated the proliferation/di erentiation program of the entire HSC/HPC population. Enforced HOXB7 expression exerted a potent stimulatory e ect on the proliferation of the primitive HPC and putative HSC subsets, assayed as HPP ± CFCs and LTC ± ICs respectively. While not modifying the total number of HPCs, exogenous HOXB7 induced an increase of the number of granulo-monocytic (GM) HPCs [colony-forming unit GM (CFU ± GM) CFU ± GM, CFU-G and CFU-M, as evaluated by clonogenic assays] and markedly ampli®ed the progeny of both CFU-G and CFU-M, which showed a sustained proliferation through at least 1 ± 2 months (as evaluated in liquid suspension culture). The prolonged proliferative stimulus induced by HOXB7 transfer into LTC, primitive and GM oriented HPC culture was characterized by persistent proliferation of a discrete population of blast cells and a large pool of di erentiated myeloid precursors. Altogether, these results suggest the hypothesis that the proliferative stimulus exerted by exogenous HOXB7 in primitive and GM-oriented HPCs may represent a preleukemic immortalization step. Consistent with the functional role of HOXB7 in the initial ontogenetic phase, these studies indicate that ectopic HOXB7 expression in early HPCs and HSCs from adult PB stimulates their self renewal, sustained proliferation and myeloid di erentiation.

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Regulation of vertebrate homeobox‐containing genes by morphogens

Cited by 75 publications

References 181 publications

Expression pattern of HOXB6 homeobox gene in myelomonocytic differentiation and acute myeloid leukemia

Expression pattern of HOXB6 homeobox gene in myelomonocytic differentiation and acute myeloid leukemia

Transduction of the SkBr3 breast carcinoma cell line with the HOXB7 gene induces bFGF expression, increases cell proliferation and reduces growth factor dependence

Enforced expression of HOXB7 promotes hematopoietic stem cell proliferation and myeloid-restricted progenitor differentiation

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