Abstract:
:Acute myeloid leukemia (AML) cells are characterized by unlimited self-renewal and an impaired capacity to undergo terminal differentiation. The MUC1 oncoprotein is aberrantly expressed in AML cells; however, there has been no evidence for involvement of MUC1 in myeloid leukemogenesis. Cell-penetrating peptide inhibitors of the MUC1-C subunit block its oligomerization and thereby oncogenic function. The present results demonstrate that treatment of human MOLM-14 and MV4-11 AML cells with these inhibitors is associated with arrest of growth, induction of late apoptosis/necrosis, and loss of self-renewal capacity. Similar results were obtained with primary blasts from patients with AML. Inhibition of MUC1-C was associated with increases in reactive oxygen species (ROS) and depletion of glutathione. Increases in ROS have been linked to induction of hematopoietic cell differentiation along the myeloid lineage. In this regard, inhibition of MUC1-C was associated with induction of a terminally differentiated myeloid phenotype in AML cell lines and primary blasts by an ROS-dependent mechanism. These findings indicate that MUC1-C function is of importance to AML cell self-renewal and that inhibition of MUC1-C represents a potential therapeutic approach to induce terminal differentiation of AML cells.
journal_name
Bloodjournal_title
Bloodauthors
Yin L,Wu Z,Avigan D,Rosenblatt J,Stone R,Kharbanda S,Kufe Ddoi
10.1182/blood-2010-10-296632subject
Has Abstractpub_date
2011-05-05 00:00:00pages
4863-70issue
18eissn
0006-4971issn
1528-0020pii
blood-2010-10-296632journal_volume
117pub_type
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