ICD-10 Specific code C92.0: Acute myeloid leukaemia

Aclarubicin is an anthracycline antibiotic produced by Streptomyces galilaeus and also has potent antineoplastic activity. It is less cardiotoxic than doxorubicin and daunorubicin. The mechanism of action of aclarubicin is based on its capacity to insert its trisaccharide chain into the minor DNA groove: poison of topoisomerase I, inhibitor of topoisomerase II, eviction of histones from nucleosomes, but also inhibitor of the 20S proteasome.

Cytarabine (ARA-C) is metabolised in vivo to ARA-CTP phosphorylated compound. This competitively inhibits DNA polymerase and may also inhibit certain acid kinase enzymes.

Daunorubicin is an anthracycline glycoside antibiotic and is a potent antileukaemic agent. It also has immunosuppressant effects. Daunorubicin may involve binding to DNA by intercalation between base pairs and inhibition of DNA and RNA synthesis by template disordering and steric obstruction.

The main effect of etoposide appears to be at the late S and early G₂ portion of the cell cycle in mammalian cells. The predominant macromolecular effect of etoposide seems to be the rupture of the double strand by an interaction with DNA-topoisomerase II or by the formation of free radicals. Etoposide has been shown to cause metaphase arrest in chick fibroblasts.

Glasdegib is an inhibitor of the Hedgehog (Hh) signal transduction pathway that binds to Smoothened (SMO), a transmembrane protein, leading to decreased Glioma-Associated Oncogene (GLI) transcription factor activity and downstream pathway signalling. Hh pathway signalling is required for maintaining a leukaemic stem cell (LSC) population thus, glasdegib binding to and inhibiting SMO reduces GLI1 levels in AML cells and the leukaemic initiating potential of AML cells.

Idarubicin is a DNA intercalating anthracycline which interacts with the enzyme topoisomerase II and has an inhibitory effect on nucleic acid synthesis. Idarubicin has been shown to have a higher potency with respect to daunorubicin and to be an effective agent against murine leukaemia and lymphomas both by i.v. and oral routes.

Ifosfamide is an antineoplastic, a cytotoxic alkylating agent. It is a prodrug and shows no in vitro cytotoxic activity until activated by microsomal enzymes. The cytotoxic activity of ifosfamide (alkylation of the nucleophilic centres in the cells) is associated with the activated oxazaphosphorine ring hydroxylated at the C4 atom which interacts with DNA-DNA cross linking. This activity manifests itself by blocking the late S and early G2 phases of the cell cycle.

Methotrexate (4-amino-10-methylfolic acid) is a folic acid antagonist which inhibits the reduction of folic acid and increase of tissue cells. Methotrexate enters the cell through an active transport mechanism of reduced folates. As a result of polyglutamation of methotrexate caused by the folylpolyglutamylate enzyme, the duration of the cytotoxic effect of the drug substance in the cell increases.

Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA.

Thiotepa is a polyfunctional cytotoxic agent related chemically and pharmacologically to the nitrogen mustard. The radiomimetic action of thiotepa is believed to occur through the release of ethylene imine radicals that, as in the case of irradiation therapy, disrupt the bonds of DNA, e.g. by alkylation of guanine at the N-7, breaking the linkage between the purine base and the sugar and liberating alkylated guanine.

Vindesine is an antineoplastic agent derived from vinblastine, like the other vinca alkaloids it causes mitotic arrest in metaphase by binding to microtubular protein.