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Table 1 Properties of the chemotherapeutic drugs used in AML

From: Deciphering molecular mechanisms underlying chemoresistance in relapsed AML patients: towards precision medicine overcoming drug resistance

Drug

Target

Influx

Metabolisma

Efflux

Refs.

Cytarabine (Ara-C)

DNA polymerases

ENT1, CNT3, OCTN1

Activation: dCK, dCMPK, NDK. Inactivation: CDA, dCMPD, PN-I.

MRP4,7,8

[14, 30,31,32,33, 78,79,80]

Daunorubicin (DNR)

DNA, Topoisomerase II

Passive diffusion

 

P-gp, MRP1,7, BCRP

[44, 51, 81,82,83,84]

Mitoxantrone (MX)

DNA, Topoisomerase II

Passive diffusion

 

P-gp, MRP1, BCRP

[44, 85,86,87,88,89,90]

Etoposide (VP-16)

Topoisomerase II

Passive diffusion

 

P-gp, MRP1-3,6, BCRP

[16, 91, 92]

Methotrexate (MTX)

DHFR, TS, AICARFT

RFC, PCFT

Aldehyde oxidase, FPGS (polyglutamylation)

P-gp, MRP1-5, BCRP

[16, 93, 94]

Venetoclax (VEN)

Bcl-2

Passive diffusion

 

P-gp

[72, 95]

Gemtuzumab Ozogamicin (GO)

DNA

Ab-mediated endocytosis

Lysosomal Calicheamicin cleavage from Ab, glutathione

P-gp, MRP1

[73, 77]

  1. DHFR, dihydrofolate reductase; TS, thymidylate synthase; AICARFT, aminoimidazole-4-carboxamide ribonucleotide formyltransferase; Bcl-2, B-cell leukemia/lymphoma 2; ENT1, equilibrative nucleoside transporter 1; CNT3, concentrative nucleoside transporter 3; OCTN1, organic cation transporter, novel, type 1; RFC, reduced folate carrier; PCFT, proton coupled folate transporter; dCK, deoxycytidine kinase; dCMPK, deoxycytidylate kinase; NDK, nucleoside diphosphate kinase; CDA, cytidine deaminase; dCMPD, deoxycytidylate deaminase; PN-I, cytosolic 5-nuleotidase 3A; FPGS, folylpoly-É£-glutamate synthetase; MRP, multidrug resistance-associated protein; P-gp, P-glycoprotein; BCRP, breast cancer resistance protein.
  2. aOccuring in leukemic cells.