Expression of -catenin by acute myeloid leukemia cells predicts enhanced clonogenic capacities and poor prognosis
Activation of the Wnt/beta-catenin pathway has recently been shown to be crucial to the establishment of leukemic stem cells in chronic myeloid leukemia. We sought to determine whether beta-catenin was correlated to clonogenic capacity also in the acute myeloid leukemia (AML) setting. Eighty-two pat...
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| Veröffentlicht in: | Leukemia 2006-07, Vol.20 (7), p.1211-1216 |
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| creator | Ysebaert, L Chicanne, G Demur, C De Toni, F Prade-Houdellier, N J-B Ruidavets V Mansat-De Mas Rigal-Huguet, F Laurent, G Payrastre, B Manenti, S Racaud-Sultan, C |
| description | Activation of the Wnt/beta-catenin pathway has recently been shown to be crucial to the establishment of leukemic stem cells in chronic myeloid leukemia. We sought to determine whether beta-catenin was correlated to clonogenic capacity also in the acute myeloid leukemia (AML) setting. Eighty-two patients were retrospectively evaluated for beta-catenin expression by Western blot. beta-Catenin was expressed (although at various protein levels) in 61% of patients, and was undetectable in the remaining cases. In our cohort, beta-catenin expression was correlated with the clonogenic proliferation of AML-colony forming cells (AML-CFC or CFU-L) in methylcellulose in the presence of 5637-conditioned medium, and more strikingly with self-renewing of leukemic cells, as assessed in vitro by a re-plating assay. In survival analyses, beta-catenin appeared as a new independent prognostic factor predicting poor event-free survival and shortened overall survival (both with P |
| doi_str_mv | 10.1038/sj.leu.2404239 |
| format | Article |
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We sought to determine whether beta-catenin was correlated to clonogenic capacity also in the acute myeloid leukemia (AML) setting. Eighty-two patients were retrospectively evaluated for beta-catenin expression by Western blot. beta-Catenin was expressed (although at various protein levels) in 61% of patients, and was undetectable in the remaining cases. In our cohort, beta-catenin expression was correlated with the clonogenic proliferation of AML-colony forming cells (AML-CFC or CFU-L) in methylcellulose in the presence of 5637-conditioned medium, and more strikingly with self-renewing of leukemic cells, as assessed in vitro by a re-plating assay. In survival analyses, beta-catenin appeared as a new independent prognostic factor predicting poor event-free survival and shortened overall survival (both with P<0.05). Furthermore, variations in beta-catenin protein levels were dependent on post-transcriptional mechanisms involving the Wnt/beta-catenin pathway only in leukemic cells. Indeed, beta-catenin negative leukemic cells were found to increase beta-catenin in response to Wnt3a agonist in contrast to normal counterparts. Altogether, our data pave the way to the evaluation of Wnt pathway inhibition as a new rationale for eradicating the clonogenic pool of AML cells.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/sj.leu.2404239</identifier><language>eng</language><publisher>London: Nature Publishing Group</publisher><subject>Bone marrow ; Leukemia ; Medical prognosis ; Stem cells</subject><ispartof>Leukemia, 2006-07, Vol.20 (7), p.1211-1216</ispartof><rights>Copyright Nature Publishing Group Jul 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2725,27922,27923</link.rule.ids></links><search><creatorcontrib>Ysebaert, L</creatorcontrib><creatorcontrib>Chicanne, G</creatorcontrib><creatorcontrib>Demur, C</creatorcontrib><creatorcontrib>De Toni, F</creatorcontrib><creatorcontrib>Prade-Houdellier, N</creatorcontrib><creatorcontrib>J-B Ruidavets</creatorcontrib><creatorcontrib>V Mansat-De Mas</creatorcontrib><creatorcontrib>Rigal-Huguet, F</creatorcontrib><creatorcontrib>Laurent, G</creatorcontrib><creatorcontrib>Payrastre, B</creatorcontrib><creatorcontrib>Manenti, S</creatorcontrib><creatorcontrib>Racaud-Sultan, C</creatorcontrib><title>Expression of -catenin by acute myeloid leukemia cells predicts enhanced clonogenic capacities and poor prognosis</title><title>Leukemia</title><description>Activation of the Wnt/beta-catenin pathway has recently been shown to be crucial to the establishment of leukemic stem cells in chronic myeloid leukemia. 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| subjects | Bone marrow Leukemia Medical prognosis Stem cells |
| title | Expression of -catenin by acute myeloid leukemia cells predicts enhanced clonogenic capacities and poor prognosis |
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