Additional file 1 of Deciphering molecular mechanisms underlying chemoresistance in relapsed AML patients: towards precision medicine overcoming drug resistance
Creators: name: Levin, May
name: Stark, Michal
name: Ofran, Yishai
name: Assaraf, Yehuda G.
Publisher: name: figshare
Year: 2021
Subjects: subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Pharmacology
subject: Biotechnology
subject: 69999 Biological Sciences not elsewhere classified
subject: Cancer
subject: Hematology
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: FOS: Health sciences
subject: 60506 Virology

description: Additional file 1: Figure. S1. Summary of drug metabolism. A graphical depiction of cellular transport, metabolism, and targets of AML chemotherapeutic drugs discussed in the manuscript. Pro-drug intermediates are colored in black, bioactive drugs are colored in light blue, and inactivated metabolites are colored in grey. Abbreviations: AICARFT, aminoimidazole-4-carboxamide ribonucleotide formyltransferase; Ara-C, cytosine arabinoside; ATP6V1H, V-type proton ATPase subunit H; Bcl-2, B-cell leukemia/lymphoma 2; Bcl-XL, apoptosis regulator Bcl-X, long isoform; BCRP, breast cancer resistance protein; CDA, cytidine deaminase; CNT3, concentrative nucleoside transporter 3; CTSD, cathepsin D; dCK, deoxycytidine kinase; dCMPD, deoxycytidylate deaminase; dCMPK, deoxycytidylate kinase; DHFR, dihydrofolate reductase; DNR, daunorubicin;ENT1, esquilibrative nucleoside transporter 1; FPGS, folylpoly-ɣ-glutamate synthetase; GO, Gemtuzumab Ozogamicin; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; Mcl-1, Induced myeloid leukemia cell differentiation protein Mcl-1; MRP, multidrug resistance-associated protein; MSMO1, methylsterol monooxygenase 1;MTX-polyG, methotrexate polyglutamate; MX, mitoxantrone; NDK, nucleoside diphosphate kinase; OCTN1, organic cation transporter, novel, type 1; PCFT, proton coupled folate transporter; P-gp, P-glycoprotein; PN-I, cytosolic 5-nuleotidase 3A; RFC, reduced folate carrier; TS, thymidylate synthase; VEN, venetoclax; VP-16, etoposide. Figure S2. Biosynthetic pathway of purine nucleotides. A graphical depiction of cellular de novo biosynthesis of purines. The enzymes that are discussed in the manuscript are colored in red. Abbreviations: ADSL, adenylosuccinate lyase;ADSS, adenylosuccinate synthase; AK, adenylate kinase; ATIC, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase; GART, phosphoribosylglycinamide formyltransferase;GMPS, guanine monphosphate synthase;GUK1, guanylate kinase 1;IMPDH, inosine 5'-monophosphate dehydrogenase;NDK, nucleoside diphosphate kinase;PAICS, phosphoribosylaminoimidazole carboxylase;PFAS, phosphoribosylformylglycinamidine synthase; PPAT, phosphoribosyl pyrophosphate amidotransferase; PRPS1, phosphoribosyl pyrophosphate synthetase 1. Figure s3. Biosynthetic pathway of pyrimidine nucleotides. A graphical depiction of cellular de novo biosynthesis of pyrimidines. Blue arrows represent pyrimidine monophosphate synthesis through the salvage pathway. The enzymes that are discussed in the manuscript are colored in red. Abbreviations: CAD, trifunctional CAD enzyme; CMPK, cytidine monophosphate (UMP-CMP) kinase 1;CTPS, CTP synthase; dCK, deoxycytidine kinase; DCTD, deoxycytidine monophosphate deaminase; DHODH, dihydroorotate dehydrogenase; DUT, deoxyuridine triphosphatase; NDK, nucleoside diphosphate kinase;UCK2, uridine-cytidine kinase 2; UMPS, uridine 5'-monophosphate synthase; RNR, ribonucleoside-diphosphate reductase; TK1, thymidine kinase 1; TMPK, thymidylate kinase; TS, thymidylate synthase. Figure S4. Cellular folate metabolism. A graphical depiction of cellular pathways utilizing folate cofactos. The enzymes that are discussed in the manuscript are colored in red. Abbreviations: ALDH1L2, aldehyde dehydrogenase 1 family, member L2; ATIC, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase;DHF, dihydrofolate; THF, tetrahydrofolate; DHFR, dihydrofolate reductase; DHFRL1, dihydrofolate reductase-like 1; GART, phosphoribosylglycinamide formyltransferase;MTHFD, methylenetetrahydrofolate dehydrogenase; MDHFD1L, methylenetetrahydrofolate dehydrogenase 1-like;MTHFR, methylenetetrahydrofolate reductase; MTHFS, 5,10-methenyltetrahydrofolate synthetase; MTR, 5-methyltetrahydrofolate-homocysteine methyltransferase; SHMT, serine hydroxymethyltransferase; TS, thymidylate synthase.