Acute Myeloid Leukemias

Question 1

What is AML?

Answer 1

Acute myeloid leukemia

• neoplasm of immature myeloid cells (myeloblasts)
• myeloblasts >20%prevalence in bone marrow
• may have Auer rods (aggregates of MPO)

Question 2

What is the common presentation of AML?

Answer 2

• most common in older adults (median age 60); can occur in all ages
• decreased bone marrow function; ie., fatigue (anemia), fever/infections (neutropenia), and bleeding (thrombocytopenia)
• petechia/ecchymoses/mucosal hemorrhage/hematuria
• opportunistic infections

Question 3

Compare ALL to AML.

Answer 3

Both have similar sympoms in their effects on bone marrow causing anemia, neutrophila, and thrombocytopenia

Non-bone marrow related symptoms are less common in AML

CNS spread occurs in both, but more frequently in ALL

Question 4

What are the FAB classifications of AML? (what is present in each)

Answer 4

Classified based of differentiation of the predominate cell (most other types will still be present):

M0: minimally differentiated; lack myleoid markers

M1: without maturation; few granules and Auer rods

M2: myelocytic maturation; granulocyte maturation, granules and Auer rods; t(8;21)

M3: promyelocytic; hypergranular promyelocytes; t(15;17)

M4: myelomonocytic maturation; MPO⁺ and nonspecific esterase⁺ (combined myelo- and mono- differentation); inv(16)

M5: monocytic; nonspecific esterase⁺ w/o Auer rods

M6: erythroid

M7: megakaryocytic; lack MPO

Question 5

What are the WHO classifications of AML? (what is present in each)

Answer 5

Class I: associated with genetic abnormalities

Class II: arose from MDS or has MDS features

Class III: therapy-related

Class IV: other (same as FAB classifications, just excluding cases with genetic causes, MDS origins, or that are therapy related)

Question 6

What type of genetic abnormalities are frequently found on Class I, II, and III of the WHO classifications?

Answer 6

Class I: rearrangements

Class II and III: deletions/monosomies

Question 7

What subtype of AML has unique tendency to infiltrate the skin and gingiva?

Answer 7

Acute monocytic leukemia

Question 8

What subtype of AML has an unusual age of presentation compared to the others?

Answer 8

Acute promyelocytic leukemia (median age 35-40)

Question 9

What subtype of AML has an increased risk of DIC?

Answer 9

Acute promyelocytic leukemia

(remember, these are the hypergraunlar type and release excess tissue factor resulting in coagulation)

Question 10

What subtype of AML is related to the t(15;17) rearrangement?

What is the fusion product?

Answer 10

Acute promyelocytic leukemia (M3)

• hypergranular -> DIC
• younger presentation (35-40)

RARα/PML

-can be treated with RA antagonist due to RAR involvement

Question 11

What subtype of AML is related to the t(8;21) rearrangement?

What is the fusion product?

Answer 11

Acute myelocytic leukemia (M2)

RUNX1/ETO

Question 12

What subtype of AML is related to the inv(16) inversion?

What is the fusion product?

Answer 12

Acute myelomonocytic leukemia (M4)

-myelocytic and monocytic differentiation

CBFB/MYH1 1

Question 13

What subtype of AML is most common with Down syndrome?

Answer 13

Acute megakaryocytic leukemia (M7)

those with Down syndrome have an increased risk of cancer, specifically AML/actue megakaryocytic leukemia

Question 14

What is the immunophenotype of AML?

Answer 14

CD34⁺ (found on multipotent stem cells but not mature cells)

CD33⁺ (found immature myeloid cells)

CD64^- (found on mature myeloid cells)

CD15^- (found on mature myeloid cells)

Question 15

What is the course/prognosis of AML subtypes?

Answer 15

• most translocations have favorable outcomes
• MDS-like have poor outcomes