The INDIVIDUALIST

A Wiki about biochemical individuality

Polymorphism

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Description

Prime source: Vigui, F . ABCB1. Atlas Genet Cytogenet Oncol Haematol. March 1998 .

Other names PGY1 (P glycoprotein1/ multidrug resistance 1 MDR1 (multidrug resistance 1) Hugo ABCB1 Location 7q21.2

P glycoprotein is a 170 kDa transmembrane glycoprotein which includes 10-15 kDa of N-term glycosylation; the N-term half of the molecule contains 6 transmembrane domains, followed by a large cytoplasmic domain with an ATP binding site, and then a second section with 6 transmembrane domains and an ATP binding site which shows over 65% of amino acid similarity with the first half of the polypeptide.

Discussion

P-Glycoprotein is a membrane glycoprotein that is associated with resistance to a variety of drugs, including many chemotherapy drugs used in cancer.

P-glycoprotein also influences the uptake of chemicals via the blood brain barrier (in the case of xenobiotics, with negative effect). It is extensively distributed and expressed in normal capillary endothelial cells comprising the blood brain barrier.

P-glycoprotein is normally expressed at secretory surface of a number of tissues, including biliary canaliculi, proximal tubules of the kidney, intestinal and colonic epithelium; hematopoietic stem cells express high levels of P-glycoprotein; overexpressed in many multidrug resistant cell lines and in tumor cells resistant to chemotherapy.

It is elevated in tumor cells resistance to a wide variety of antineoplasic agents: doxorubicin, daunorubicin, vinblastine, vincristine, colchicine, actinomycine D, etoposide, tenoposide, mitoxantrone, homoharringtonine; this phenomenon is named "multidrug resistance" (MDR); P-glycoprotein is the main protein responsible for the MDR phenotype; however, other agents may be involved in MDR, independently or in association with P-glycoprotein: "multidrug resistant associated protein" (MRP), "lung resistance protein" (LRP), "anthracycline associated resistance protein" (ARX).

In leukemia, MDR1 overexpression is observed in patients with a lower complete remission rate and with a shortening of overall survival; frequently associated with intermediate and poor prognosis karyotype; in ANLL, approximately 50% of patients are MDR positive at diagnosis (range 22-70%) and the MDR phenotype is more frequently observed in CD34+ leukemias; in ALL, the average number of MDR-positive cases is 22% at diagnosis.

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