Abstract
Expression of MDR1 is a well-characterized mechanism leading to resistance of tumor cells to drugs like vinca-alkaloids, anthracyclines, and epipodophyllotoxins. In hematopoiesis, recent data indicate that not only leukemic cells, but also some populations of normal hematopoietic cells, particularly CD34+ progenitor cells as well as peripheral blood lymphocytes, express a functional multidrug-resistant phenotype. Among CD34+ cells, we found evidence that myeloid committed precursor cells (CD34+/CD33+) have lower levels of MDR1 expression than earlier CD34+ cell populations, but there was no difference in MDR1 expression between CD34+/HLA-DR- and CD34+/HLA-DR+ subpopulations. During normal myeloid differentiation, MDR1 expression is down-regulated, which is similar to our observations in acute myelogenous leukemia (AML): MDR1 expression was only rarely detected in acute promyelocytic leukemia, which was in contrast to other subtypes of AML; also, within leukemic subpopulations of the same patient, higher MDR1 levels were correlated with a more immature immunophenotype. Regarding regulation of MDR1 expression, we did not observe changes of MDR1 expression in normal CD34+ cells in response to various cytokines. However, in 2 patie...Continue Reading
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