Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of P-glycoprotein (Pgp), the product of the multidrug resistance (MDR1) gene, detected by flow cytometric analysis of the binding of antibody 4E3.16, was found on significantly fewer leukemic cells in 35 adult patients with de novo acute promyelocytic leukemia (APL) (mean 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 the chimeric fusion transcript PML/RAR alpha by PCR. To further substantiate low MDR1 expression in APL, we studied cells from 11 APL patients at the molecular and functional level in comparison to 48 non-APL cases. The diagnosis of APL was associated with the absence of Pgp function by the rhodamine efflux assay (p = 0.0001). Furthermore, MDR1-specific transcript levels, determined by quantitative PCR with two distinct sets of primers, were significantly lower in mononuclear cells from the APL than the other AML cases (p = 0.013). The frequency of leukemic cells positive for CD34, an antigen presumably associated with Pgp expression in AML, was significantly lower in APL than other AMLs (p = 0.0001). In contrast to non-APL leukemias, those few cases of CD34 strongly positive APL neither expressed Pgp nor contained significant MDR1 transcript levels. Low expression of Pgp by APL cells may provide the biologic basis for the high sensitivity of this leukemia subtype to chemotherapeutic agents in vivo.
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PMID:Significantly lower P-glycoprotein expression in acute promyelocytic leukemia than in other types of acute myeloid leukemia: immunological, molecular and functional analyses. 751 29

In 452 adult patients with de novo acute myeloid leukemia (AML), a series of 22 monoclonal antibodies was used to identify immunophenotypic characteristics of acute promyelocytic leukemia (APL) as compared to other AMLs (groups FAB M1/M2 and M4/M5). Only those patients with FAB M3 cytology were included in the analysis for which APL was confirmed by the presence of the t(15;17) cytogenetic aberration and the detection of the PML/RAR alpha gene fusion transcript by PCR amplification (35 cases). Significantly fewer APL blast cells were positive for the stem cell antigen, CD34 (p = 0.0001) as well as for HLA-DR (p < 0.0001). With respect to myeloid antigens, APLs less frequently expressed the myelomonocytic antigens, CD11b (p = 0.0001) and CD14 (p = 0.0013), whereas expression of CD33, a pan-myeloid marker, was more frequent in APL (p = 0.0001). CD15, the X-hapten carbohydrate structure (lacto-N-fucopentaose-III), typically expressed at the maturation stage of normal promyelocytes, was found to be sialylated on APL blasts as recognized by differential binding of the anti-CD15 antibodies, VIM-D5 (non-sialylated CD15) and VEP-9 (sialylated CD15). Expression of the T-cell associated CD7 antigen was rarer on APL than non-APL cells (p = 0.0001), as was that of the multidrug resistance P-glycoprotein (p = 0.0038). Marginal correlations existed between antigen profile (particularly CD2) and the type of PML/RAR alpha transcripts. In addition to its unique genotypic features, these data establish APL as a distinct immunophenotypic entity.
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PMID:The immunophenotype of acute promyelocytic leukemia (APL): an ECOG study. 803 2