Abstract：
:Acute myeloid leukemia (AML) is a malignancy of stem cells with an unlimited capacity for self-renewal. MUC1 is a secreted, oncogenic mucin that is expressed aberrantly in AML blasts, but its potential uses to target AML stem cells have not been explored. Here, we report that MUC1 is highly expressed on AML CD34(+)/lineage(-)/CD38(-) cells as compared with their normal stem cell counterparts. MUC1 expression was not restricted to AML CD34(+) populations as similar results were obtained with leukemic cells from patients with CD34(-) disease. Engraftment of AML stem cell populations that highly express MUC1 (MUC1(high)) led to development of leukemia in NOD-SCID IL2Rgamma(null) (NSG) immunodeficient mice. In contrast, MUC1(low) cell populations established normal hematopoiesis in the NSG model. Functional blockade of the oncogenic MUC1-C subunit with the peptide inhibitor GO-203 depleted established AML in vivo, but did not affect engraftment of normal hematopoietic cells. Our results establish that MUC1 is highly expressed in AML stem cells and they define the MUC1-C subunit as a valid target for their therapeutic eradication.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Stroopinsky D,Rosenblatt J,Ito K,Mills H,Yin L,Rajabi H,Vasir B,Kufe T,Luptakova K,Arnason J,Nardella C,Levine JD,Joyce RM,Galinsky I,Reiter Y,Stone RM,Pandolfi PP,Kufe D,Avigan Ddoi
10.1158/0008-5472.CAN-13-0677subject
Has Abstractpub_date
2013-09-01 00:00:00pages
5569-79issue
17eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-13-0677journal_volume
73pub_type
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