HoxB8 requires its Pbx-interaction motif to block differentiation of primary myeloid progenitors and of most cell line models of myeloid differentiation

Knoepfler, Paul S.; Sykes, David B.; Pasillas, Martina P.; Kamps, Mark P.

doi:10.1038/sj.onc.1204710

Cited by 54 publications

(57 citation statements)

References 44 publications

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“…Up-regulation of HoxC8 and HoxB8 in colorectal cancer was reported as early as 1997, however the relevance of those genes for carcinogenesis had not been analyzed [26] . A relevant leukemogenic property of HoxB8 mediated through inhibition of differentiation has been described for acute myeloid leukemia [27,28] . These data are intriguing, as low concentrations of miR-196a completely restrict HoxB8, thus erasing the prooncogenic and leukemogenic effects of HoxB8.…”

Section: Discussionmentioning

confidence: 99%

High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells

Schimanski¹,

Frerichs²,

Rahman³

et al. 2009

WJG

183

147

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Section: Discussionmentioning

confidence: 99%

High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells

Schimanski¹,

Frerichs²,

Rahman³

et al. 2009

WJG

183

147

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“…Stable RAW264.7 transfectants were generated and cultured as described 25 . Fetal liver myeloid progenitors were immortalized using an oestrogen-responsive ER-HoxB8 oncogene in the presence of 1 mM oestrogen and GM-CSF 21 . Reagents and plasmids.…”

Section: Methodsmentioning

confidence: 99%

“…Notably, the TBK1 interactor TANK/i-TRAF 19 is also a TRAF2/3-interacting protein 20 . To examine the role of TRAF3 in recruiting TBK1 to TIR complexes, we immortalized Traf3 2/2 fetal liver myeloid progenitors with a retrovirus expressing the HoxB8 oncogene 21 . These cells were transduced with the MyD88-GyrB fusion construct.…”

mentioning

confidence: 99%

Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6

Häcker

Redecke²,

Blagoev

et al. 2005

Nature

846

736

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“…Several laboratories have taken advantage of the ability of homeobox-containing genes to block myeloid differentiation, and have thereby obtained primary myeloid precursors that can be maintained in culture for long periods of time, providing unlimited numbers of cells. [15][16][17][18] Although these lines have proven useful for the study of homeoproteins and their cofactors, their utility as models to investigate leukemic progression is unknown, as they have either not yet been characterized in vivo [16][17][18] or have no reported potential to be converted into AML-inducing cells. 15 Thus, the availability of lines with documented repopulating potential and capacity for leukemic conversion would open a new path for the understanding of the progression of Hox-mediated AML.…”

Section: Introductionmentioning

confidence: 99%

Transplantable cell lines generated with NUP98–Hox fusion genes undergo leukemic progression by Meis1 independent of its binding to DNA

2005

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Hox genes have been identified in chromosomal translocations involving the nucleoporin gene NUP98. Though the resulting chimeric proteins directly participate in the development of leukemia, the long latency and monoclonal nature of the disease support the requirement for secondary mutation(s), such as those leading to overexpression of Meis1. Models to identify such events and to study leukemic progression are rare and labor intensive. Herein, we took advantage of the strong transforming potential of NUP98-HOXD13 or NUP98-HOXA10 to establish preleukemic myeloid lines from bone marrow cells that faithfully replicate the first step of Hox-induced leukemogenesis. These lines contain early granulomonocytic progenitors with extensive in vitro self-renewal capacity, short-term myeloid repopulating activity and low propensity for spontaneous leukemic conversion. We exploit such lines to show that Meis1 efficiently induces their leukemic progression and demonstrate a high frequency of preleukemic cells in the cultures. Furthermore, we document that the leukemogenic potential of Meis1 is independent of its direct binding to DNA and likely reflects its ability to increase the repopulating capacity of the preleukemic cells by increasing their selfrenewal/proliferative capacity. The availability of lines with repopulating potential and capacity for leukemic conversion should open new avenues for understanding progression of Hox-mediated acute myeloid leukemia.

show abstract

HoxB8 requires its Pbx-interaction motif to block differentiation of primary myeloid progenitors and of most cell line models of myeloid differentiation

Cited by 54 publications

References 44 publications

High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells

High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells

Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6

Transplantable cell lines generated with NUP98–Hox fusion genes undergo leukemic progression by Meis1 independent of its binding to DNA

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