Several hypotheses for decreased drug accumulation in resistant parasites have been proposed, including one analogous of the drug efflux pump model of drug resistant tumor cells, the increased expression of conserved type of protein called P-glycoprotein (p-gp) that has been one of the most consistent changes detected in drugresistant tumor cells.[22] The first MDR homologous gene discovered in Leishmania, LTPGPA, was an extra chromosomal circle (H-circle) amplified in a methotrexate resistant L. tarentolae promastigote cell line. Here, PGP is linked to neoplasm.