Acute Myeloid Leukaemia Classification and Cytogenetics
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Direct answer
Acute myeloid leukaemia is a clonal myeloid neoplasm defined by at least 20 percent myeloblasts in the classical (WHO 2016) criteria, and it is now classified by recurrent genetic abnormalities as well as morphology. Favourable karyotypes such as t(8;21), inv(16) and t(15;17) respond well to induction, whereas complex karyotype, loss of chromosome 5 or 7 and t(6;9) carry adverse prognosis and usually prompt transplant consideration.
What you must remember
- Blast threshold: at least 20 percent myeloblasts defines AML in classical criteria, but t(15;17), t(8;21) and inv(16) establish AML regardless of blast count; WHO 2022 and ICC 2022 relax the threshold further.
- Auer rods: needle-like cytoplasmic inclusions specific to the myeloid lineage, so their presence supports AML over ALL.
- Myeloperoxidase and Sudan black B: positive in myeloid blasts, which helps distinguish AML from lymphoblastic leukaemia.
- t(15;17): PML-RARA fusion in acute promyelocytic leukaemia, treated with all-trans retinoic acid and arsenic trioxide, with a high risk of disseminated intravascular coagulation.
- t(8;21) and inv(16): RUNX1-RUNX1T1 and CBFB-MYH11 fusions respectively, both favourable and responsive to chemotherapy.
- Adverse cytogenetics: complex karyotype, -5 or 5q deletion, -7, t(6;9), t(9;22), inv(3) and KMT2A rearrangements other than t(9;11).
- FLT3 and NPM1: under ELN 2022, NPM1 mutation without FLT3-ITD is favourable, whereas FLT3-ITD moves it to intermediate risk (the older allelic-ratio rule is dropped).
- Induction: the 7+3 regimen, cytarabine for seven days with an anthracycline for three days, aims for complete remission with fewer than 5 percent blasts.
A stepwise approach to a new diagnosis
A new AML diagnosis is built from morphology, immunophenotype and genetics, and promyelocytic disease is recognised first because it is an emergency. The steps below follow that order.
- Confirm the blast count and lineage: count marrow blasts and check myeloperoxidase or Sudan black B positivity, using the 20 percent threshold, which genetic lesions such as t(15;17), t(8;21) and inv(16) override.
- Look for APL first: a promyelocytic picture with faggot cells and bleeding prompts immediate PML-RARA testing, and all-trans retinoic acid is started without waiting for the result.
- Refine by immunophenotype: Auer rods, monocytic differentiation and flow cytometry for CD13, CD33, CD117 and HLA-DR refine the diagnosis.
- Send cytogenetics and molecular tests: karyotype and fusion testing, with NPM1, FLT3 and CEBPA, determine risk.
- Assign the ELN risk group: combine karyotype and mutations into favourable, intermediate or adverse groups.
- Start induction: the 7+3 regimen aims for complete remission, assessed by marrow examination after the first course.
- Plan consolidation and transplant: favourable-risk patients usually receive chemotherapy consolidation, while adverse or selected intermediate-risk patients are considered for allogeneic transplant in first remission.
Where the exam tries to catch you
AML questions reward the candidate who connects a cytogenetic abnormality to its treatment and prognosis.
- Trap: applying the 20 percent threshold strictly to acute promyelocytic leukaemia Correct: t(15;17) defines APL regardless of blast count, and it needs immediate all-trans retinoic acid.
- Trap: reading Auer rods as evidence of lymphoblastic leukaemia Correct: Auer rods are myeloid-specific, so their presence favours AML over ALL.
- Trap: routinely offering transplant in first remission for t(8;21) Correct: favourable karyotypes respond well to chemotherapy consolidation, so transplant is not routine.
- Trap: using all-trans retinoic acid for every AML Correct: retinoic acid is specific to APL, while other subtypes need standard 7+3 induction.
Frequently asked questions
Which AML subtype is treated with all-trans retinoic acid and arsenic trioxide?
Acute promyelocytic leukaemia, carrying the t(15;17) PML-RARA fusion, is treated with all-trans retinoic acid and arsenic trioxide. Coagulopathy and disseminated intravascular coagulation require early management alongside these drugs.
Why are Auer rods important in acute myeloid leukaemia?
Auer rods are needle-like cytoplasmic inclusions specific to the myeloid lineage, so their presence supports AML over ALL. They are most abundant in acute promyelocytic leukaemia, where the blasts are called faggot cells.
Which karyotypes are favourable in acute myeloid leukaemia?
Favourable karyotypes include t(8;21) with RUNX1-RUNX1T1, inv(16) or t(16;16) with CBFB-MYH11, and t(15;17) with PML-RARA. Mutated NPM1 without FLT3-ITD is also favourable under ELN 2022, and these groups respond well to induction.
What is the standard induction regimen for acute myeloid leukaemia?
The standard induction regimen is 7+3, which combines cytarabine for seven days with an anthracycline such as daunorubicin or idarubicin for three days. It aims to achieve complete remission, with fewer than 5 percent blasts in the marrow.
Which cytogenetic abnormalities carry adverse prognosis in acute myeloid leukaemia?
Complex karyotype, loss of chromosome 5 or 5q, loss of chromosome 7, t(6;9), t(9;22), inv(3) and KMT2A rearrangements other than t(9;11) carry adverse prognosis. Patients with these abnormalities are usually considered for allogeneic transplant in first remission.