Journal of Blood Research & Hematologic Diseases

All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.

The Role of Wnt/β -Catenin Signaling in Normal and Malignant Hematopoiesis, Hemostasis

The Wnt/β-catenin signaling plays indispensable roles in embryonic development and adult homeostasis. Through diverse mechanisms which are partially defined, abnormal activation of β-catenin occurs frequently in neoplastic disease. A critical function for Wnt/β-catenin in solid tumors, in particular colorectal cancer, has been well characterized. Increasing evidence indicates that this pathway is also deregulated in hematological malignancies. In acute myeloid leukemia, enhanced β-catenin levels are observed in a large proportion of patients, and correlates with increased blast clonogenicity and poor outcome. Similarly, in chronic myeloid leukemia (CML), Wnt/β-catenin activation is observed in advanced disease, and inhibition of β-catenin in vivo potentiates the effect of tyrosine kinase inhibitors in mouse models of CML. While studies suggest that β-catenin may be dispensable for steady-state maintenance of adult hematopoietic stem cells, a critical function for this pathway in regulation of specialized leukemic stem cells (LSC) is emerging. Here we review the currently understood mechanisms and roles of β-catenin in hematological malignancies, and describe the evidence outlining the contribution of β-catenin activation in mediating the self-renewal and drug-resistant properties of LSC. In addition, given the implication of LSC in disease relapse, we discuss current approaches and limitations of targeting the Wnt/β-catenin axis in the clinic.

Special Features

Full Text

View

Track Your Manuscript

Media Partners

GET THE APP