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Acute myeloid leukemia cell beta-catenin expression predicts poor prognosis

09-19-2006

According to recently published research from France, "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," wrote L. Ysebaert and colleagues at CHU Purpan in Toulouse, "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 replating 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," continued scientists, "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."

The authors concluded, "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."

Ysebaert and colleagues published their study in Leukemia (Expression of beta-catenin by acute myeloid leukemia cells predicts enhanced clonogenic capacities and poor prognosis. Leukemia, 2006;20(7):1211-1216).

For additional information, contact L. Ysebaert, CHU Purpan, Service Hematology Clinic, 1 Pl Dr. Baylac, F-31059 Toulouse 9, France.

The publisher of the journal Leukemia can be contacted at: Nature Publishing Group, Macmillan Building, 4 Crinan St., London N1 9XW, England.

Keywords: Toulouse, France, Acute Myeloid Leukemia, Beta-Catenin, Prognostic Indicator, Clonogenic Capacity, Event-Free Survival.

This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2006, Clinical Oncology Week via NewsRx.com.