Acute Myeloid Leukemia Genetics

Question 1

Why is it so critical to quickly diagnose Acute Promyelocytic Leukemia (APL)?

Answer 1

Its propensity to be associated with devastating hemorrhagic events.

Question 2

The characteristic cytogenetic abnormality in APL is….

Answer 2

t(15;17)(q22;q12), PML-RARA

Question 3

Name three AML subtypes where the blast count can be <20% in blood or bone marrow and still be diagnosed.

Answer 3

Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12), PML-RARA

AML with t(8;21)(q22;q22), RUNX1-RUNX1T1

AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22), CBFB-MYH11

Question 4

Answer 4

APL

Consists of numerous cytologically atypical cells that resemble promyelocytes, frequently containing single or multiple Auer rods, nuclear bilobation, sometimes with “sliding-plate”, “coin-on-coin” or “butterfly-shaped” nuclei, with a thin nuclear isthmus connecting the more bulbous nuclear lobes.

Question 5

Two acute myeloid leukemias referred to as core-binding factor (CBF) AML?

Answer 5

Acute myeloid leukemia with t(8;21) and inv(16).

RUNX1(rearranged in t[8;21]) and CBFB (rearranged in inv[16]) are both subunits of the CBF transcription complex, which is critical for myeloid differentiation.

Question 6

Answer 6

Acute myeloid leukemia with t(8;21) featuring large blasts with a prominent perinuclear hof, occasional large cytoplasmic salmon-colored granules, and frequent fine Auer rods.

Question 7

Answer 7

Acute myeloid leukemia with inv(16) exhibits myelomonocytic features and a population of eosinophils and precursors with abnormal basophilic granulation

Question 8

List some well-known prognostic AML cytogentic and gene mutations.

Answer 8

Question 9

Answer 9

AML with cup-shaped nuclear morphology are strongly associated with cooccurring mutations of NPM1 (internal tandem repeats within juxtamembrane domain or activating point mutations in the tyrosine kinase domain) and FLT3 (typically insertions or deletions of 4-9 bp).

This morphology can be associated with solitary NPM1 but generally not FLT3 mutation on its own.

Question 10

Describe characteristics of AML with CEBPA mutation(s)

Answer 10

Bone marrow aspirate smears reveal increased blasts with frequent Auer rods, core biopsy contains hypercellular bone marrow replaced by sheets of blasts.

Molecular findings can include biallelic N-terminal mutation and C-terminal mutation.

Flow cytometric analysis reveals blasts with aberrant CD7 expression.