In most cases of acute myeloid leukemia (AML) malignant stem cells are considered to be within the CD34þCD38À population. The involvement of CD34þCD38À cells in leukemogenesis is suggested by the presence of cytogenetically aberrant cells in the stem cell compartment in AML, as demonstrated by PCR and FISH for leukemia specific translocations. Furthermore, transplantation studies using NOD/SCID mice have shown that cells with leukemic engraftment and self renewal potential are exclusively found within the CD34þCD38À cell population and not in more differentiated CD34þCD38þ populations. 1 Incomplete eradication of these primitive cells may eventually lead to disease relapse. Multidrug resistance induced by the expression of ATP binding cassette (ABC) transporters may hamper the eradication of these primitive leukemic cells.

ABC transporters represent the largest family of transmembrane proteins involved in the transport of a wide variety of substrates across biological membranes, including phospholipids, ions, peptides, steroids, polysaccharides, amino acids, organic anions, bile acids, drugs and other xenobiotics. Currently, the ABC superfamily consists of 48 members; that can be divided into seven subfamilies based on similarity in protein structure (ABCA, B, C, D, E, F and G). Some of these transporters (ABCB1, ABCC1 and ABCG2) are expressed at high levels on hematopoietic primitive cells. 2 The physiological function of ABC transporters in human stem cell biology is not well understood. A role for ABC transporters in the protection from genetic damage by naturally occurring xenobiotics has been suggested for hematopoietic stem cells. 3 This has recently been substantiated by the observation of increased sensitivity to xenobiotics in normal bone marrow cells in ABCB1 and ABCG2/BCRP knockout mice.