• AML with myelodysplasia-related gene mutations (AML-MR): Eight genes (ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1 and ZRSR2) are almost never mutated in leukaemia that arises out of nowhere but are typical of leukaemia that grew out of a smouldering marrow disorder; finding one on the diagnostic gene panel labels the AML as myelodysplasia-related, puts it in the adverse-risk group and changes the chemotherapy chosen.
• From a clone in the blood to a leukaemia: what is known, and what is done: Chemotherapy and radiotherapy select for blood stem cells carrying particular mutations, and in a small minority one of those clones becomes a leukaemia.
• Alkylating agents and therapy-related myeloid neoplasms: Alkylating chemotherapy can damage a blood stem cell in a way that shows up years later as myelodysplastic syndrome or acute myeloid leukaemia.
• Topoisomerase II inhibitors and the shorter latency: Etoposide and the anthracyclines can cause a leukaemia too, but a different one: it arrives after about two years rather than six, it starts as acute leukaemia without a myelodysplastic phase, and it carries a balanced break in a chromosome rather than a missing piece.
• Hypomethylating agents (azacitidine, decitabine): Low-intensity chemotherapy that strips chemical 'off' switches (methyl groups) from DNA so silenced genes can be read again.
• SF3B1 mutation: SF3B1 is a splicing gene whose mutation makes the marrow produce red cells with iron-stuffed mitochondria (ring sideroblasts); in myelodysplastic syndrome it defines a low-risk subtype with anaemia that responds to luspatercept, whereas in CLL and uveal melanoma the same mutation has different, mostly adverse or delayed-relapse, meaning.
• ELN 2022 risk classification: The three-tier system (favourable, intermediate, adverse) that decides how aggressively an adult with AML is treated and whether a transplant is recommended.
• TP53-mutated (p53-abnormal): Loss of the p53 'guardian of the genome', the most commonly mutated gene in cancer.
• Secondary malignancy (therapy-related cancer): A new, different cancer caused by the treatment of the first one: leukaemia after alkylating chemotherapy or PARP inhibitors, solid tumours in irradiated tissue decades later, and rarely T-cell lymphoma after CAR-T.

Newly diagnosed, fit for intensive chemotherapy, age 60 to 75: CPX-351 induction (Study 301) followed by allogeneic transplant in remission; 7+3 where CPX-351 is unavailable.

Newly diagnosed, unfit for intensive chemotherapy: Venetoclax plus azacitidine or decitabine; hypomethylating agent alone for TP53-mutated disease where venetoclax adds little; trials.

Biomarker results to ask for: TP53 mutation and allelic state, Complex or monosomal karyotype, Myelodysplasia-related mutations (SRSF2, SF3B1, ASXL1, RUNX1, U2AF1, EZH2, BCOR, STAG2), KMT2A rearrangement, Prior clonal haematopoiesis, ELN 2022 risk group.

Bring copies of scan reports, pathology and blood results, and a list of every medicine and supplement.

• Consolidation and relapse: Allogeneic transplant is the only curative option; genotype-directed drugs where a FLT3, IDH or KMT2A target exists. (Allogeneic stem cell transplantation, Gilteritinib, Ivosidenib, Revumenib)

From the standard of care recorded for this cancer; which apply depends on your stage and biomarkers. Ask which the team recommends and why.