SIGNIFICANTLY LOWER P-GLYCOPROTEIN EXPRESSION IN ACUTE PROMYELOCYTIC LEUKEMIA THAN IN OTHER TYPES OF ACUTE MYELOID-LEUKEMIA - IMMUNOLOGICAL, MOLECULAR AND FUNCTIONAL ANALYSES

Expression of P-glycoprotein (Pgp), the product of the multidrug resis tance (MDR1) gene, detected by flow cytometric analysis of the binding of antibody 4E3.16, was found on significantly fewer leukemic cells i n 35 adult patients with de novo acute promyelocytic leukemia (APL) (m ean 14.8%, median 7%) than in 184 patients with non-APL acute myeloid leukemia (AML) at diagnosis (mean 28.3%, median 18%) (p = 0.0038). APL was diagnosed based on morphology, the detection of t(15;17) and of t he chimeric fusion transcript PML/RAR alpha by PCR. To further substan tiate low MDR1 expression in APL, we studied cells from 11 APL patient s at the molecular and functional level in comparison to 48 non-APL ca ses. The diagnosis of APL was associated with the absence of Pgp funct ion by the rhodamine efflux assay (p=0.0001). Furthermore, MDR1-specif ic transcript levels, determined by quantitative PCR with two distinct sets of primers, were significantly lower in mononuclear cells from t he APL than the other AML cases (p=0.013). The frequency of leukemic c ells positive for CD34, an antigen presumably associated with Pgp expr ession in AML, was significantly lower in APL than other AMLs (p = 0.0 001). In contrast to non-APL leukemias, those few cases of CD34 strong ly positive APL neither expressed Pgp nor contained significant MDR1 t ranscript levels. Low expression of Pgp by APL cells may provide the b iologic basis for the high sensitivity of this leukemia subtype to che motherapeutic agents in vivo.