Targeting cell-bound MUC1 on myelomonocytic leukemias and leukemic stem cells: Therapeutic implications.

Abstract

e14003Background: Monocytic neoplasms,include chronic myelomonocytic leukemia (CMML), acute myelomonocytic and monocytic leukemia, and monocytic sarcoma. Cell surface molecules overexpressed by leukemic cells represent potential disease-specific therapeutic targets..MUC1 has an extracellular domain containing tandem repeats of a 20 amino acid-long sequence, a transmembrane domain, and a short cytoplasmic tail. Cleavage of MUC1 yields an extracellular alpha subunit containing the tandem repeat and a smaller beta subunit. Anti-MUC1 Abss reported to date target the highly immunogenic tandem repeat of the MUC1 alpha chain. However the alpha chain is cell-bound only intermittently to MUC1+ cells. In contrast, the MUC1 SEA domain remains fixed to the cell surface. Methods: A series of 22 AML samples (AML0 = 2, AML1 = 2, AML2 = 10, AML4 = 1, AML5 = 5, AML6 = 2) collected either at the time of diagnosis or at relapse were analysed for MUC1 expression by flow cytometry. A murine mammary tumor cell line transfected...