AML Flashcards
Which clinical syndrome associated with trisomy 21 (Down syndrome) increases the risk of acute megakaryocytic leukemia (AML) in children under 4 years of age?
A) Diamond-Blackfan anemia
B) Shwachman-Diamond syndrome
C) Dyskeratosis congenita
D) Down syndrome–associated AML
Answer: D) Down syndrome–associated AML
Rationale: Down syndrome with trisomy 21 increases the risk of acute megakaryocytic AML in young children, which is often associated with mutations in the GATA1 gene.
Which of the following genetic syndromes is characterized by defective DNA repair and is associated with an increased risk of AML?
A) Fanconi anemia
B) Diamond-Blackfan anemia
C) Shwachman-Diamond syndrome
D) Kostmann syndrome
Answer: A) Fanconi anemia
Rationale: Fanconi anemia is a DNA repair disorder associated with a higher risk of AML. Other DNA repair disorders, such as Bloom syndrome and ataxia-telangiectasia, also increase AML risk.
What mutation is most commonly associated with AML in children with Down syndrome?
A) RUNX1
B) GATA1
C) DDX41
D) ANKRD26
Answer: B) GATA1
Rationale: GATA1 mutations are commonly associated with AML in children with Down syndrome.
Which anticancer drug class is associated with AML characterized by multilineage dysplasia and chromosome 5 and 7 abnormalities?
A) Alkylating agents
B) Topoisomerase II inhibitors
C) Antimetabolites
D) Immune checkpoint inhibitors
Answer: A) Alkylating agents
Rationale: Therapy-associated AML from alkylating agents occurs 4–6 years after exposure and is often associated with multilineage dysplasia and monosomy or other abnormalities involving chromosomes 5 and 7.
Topoisomerase II inhibitor–associated AML typically occurs:
A) Immediately after treatment
B) 1–3 years after treatment
C) 4–6 years after treatment
D) 8–10 years after treatment
Answer: B) 1–3 years after treatment
Rationale: AML associated with topoisomerase II inhibitors generally arises 1–3 years after exposure and is linked to monocytic AML features with aberrations involving chromosome 11q23.
Which of the following is a feature of alkylating agent–associated AML compared to topoisomerase II inhibitor–associated AML?
A) Occurs sooner after treatment
B) Commonly involves chromosome 11q23
C) Is associated with multilineage dysplasia
D) Affects primarily monocytic lineages
Answer: C) Is associated with multilineage dysplasia
Rationale: Alkylating agent–associated AML is characterized by multilineage dysplasia and monosomy/aberrations in chromosomes 5 and 7, while topoisomerase II inhibitors are associated with monocytic features and chromosome 11q23 abnormalities.
What is the minimum bone marrow (or blood) blast percentage required for an AML diagnosis according to the WHO classification (except for specific genetic abnormalities)?
A) 10%
B) 15%
C) 20%
D) 25%
Answer: C) 20%
Rationale: A marrow or blood blast count of ≥20% is required to establish the diagnosis of AML, except for cases with specific recurrent genetic abnormalities.
Which of the following genetic abnormalities allows an AML diagnosis without meeting the ≥20% blast threshold?
A) t(8;21)
B) t(9;22)
C) monosomy 5
D) inv(3)
Answer: A) t(8;21)
Rationale: The WHO classification includes exceptions to the ≥20% blast count rule for AML with specific recurrent genetic abnormalities, such as t(15;17), t(8;21), inv(16), or t(16;16).
Which of the following genetic translocations is associated with acute promyelocytic leukemia (APL)?
A) t(15;17)
B) t(8;21)
C) inv(16)
D) t(16;16)
Answer: A) t(15;17)
Rationale: Acute promyelocytic leukemia (APL) is characterized by the t(15;17) translocation, which involves the PML-RARA fusion gene.
Which chromosomal abnormality in AML is associated with the best prognosis?
A) t(8;21)
B) t(15;17)
C) inv(16)
D) t(6;9)
Answer: B) t(15;17)
Rationale: AML with t(15;17), associated with acute promyelocytic leukemia, has the best prognosis, with approximately 85% of patients achieving a cure.
Which of the following is considered a very poor prognostic factor in AML?
A) t(15;17)
B) inv(16)
C) TP53 mutation
D) No cytogenetic abnormality
Answer: C) TP53 mutation
Rationale: TP53 mutations, complex karyotypes, and certain chromosomal abnormalities (e.g., t(6;9), inv(3), or –7) are associated with a very poor prognosis in AML.
Which mutation is most commonly associated with AML patients who have a complex karyotype and very poor outcomes?
A) RUNX1 mutation
B) TP53 mutation
C) NPM1 mutation
D) FLT3-ITD mutation
Answer: B) TP53 mutation
Rationale: TP53 mutations are frequently observed in patients with complex karyotypes and are strongly associated with very poor outcomes in AML.
What is the mainstay of induction chemotherapy for AML (excluding APL)?
A) Cytarabine and an anthracycline
B) Azacitidine and venetoclax
C) Gemtuzumab ozogamicin monotherapy
D) High-dose methotrexate
Answer: A) Cytarabine and an anthracycline
Rationale: The standard induction therapy for AML consists of a combination of cytarabine and an anthracycline (e.g., daunorubicin or idarubicin), commonly referred to as the “7 + 3 regimen.”
What is the mechanism of action of cytarabine?
A) DNA intercalation
B) Inhibition of topoisomerase II
C) S-phase–specific inhibition of DNA synthesis
D) Blocking microtubule assembly
Answer: C) S-phase–specific inhibition of DNA synthesis
Rationale: Cytarabine is a cell cycle S-phase–specific antimetabolite. It becomes phosphorylated to an active triphosphate form that interferes with DNA synthesis.
Which targeted agent can be added to induction therapy for CBF AML?
A) Azacitidine
B) Gemtuzumab ozogamicin
C) Venetoclax
D) Sorafenib
Answer: B) Gemtuzumab ozogamicin
Rationale: The CD33-targeting immunoconjugate gemtuzumab ozogamicin may be added to induction therapy, particularly for core-binding factor (CBF) AML.
What is the next step if a patient fails to achieve remission after the first induction cycle?
A) Bone marrow transplant immediately
B) Reinduction with the same or modified therapy
C) Observation without additional therapy
D) Switch to high-dose methotrexate
Answer: B) Reinduction with the same or modified therapy
Rationale: If remission is not achieved after the first cycle of induction therapy, reinduction with the same or slightly modified regimen is offered.
What is the mechanism of action of all-trans-retinoic acid (ATRA) in APL?
A) Induction of apoptosis in leukemic cells
B) Differentiation of leukemic cells bearing the t(15;17)
C) Inhibition of topoisomerase II
D) Inhibition of DNA synthesis
Answer: B) Differentiation of leukemic cells bearing the t(15;17)
Rationale: ATRA promotes differentiation of promyelocytic leukemia cells with the t(15;17) translocation.
What is a common early complication of ATRA therapy in APL?
A) Febrile neutropenia
B) APL (differentiation) syndrome
C) Tumor lysis syndrome
D) Hemophagocytic syndrome
Answer: B) APL (differentiation) syndrome
Rationale: APL syndrome is characterized by fever, fluid retention, dyspnea, and pulmonary infiltrates, and is related to adhesion of differentiated leukemic cells to the endothelium.
What is the first-line treatment for low-risk APL?
A) Cytarabine and daunorubicin
B) ATRA plus arsenic trioxide (ATO)
C) ATRA plus idarubicin chemotherapy
D) ATO monotherapy
Answer: B) ATRA plus arsenic trioxide (ATO)
Rationale: For low-risk APL, ATRA/ATO has been shown to be superior and is now the standard of care.
Which of the following is a life-threatening complication associated with APL syndrome?
A) Hypoxemia and pulmonary infiltrates
B) Tumor lysis syndrome
C) Febrile neutropenia
D) Graft-versus-host disease
Answer: A) Hypoxemia and pulmonary infiltrates
Rationale: APL syndrome involves hypoxemia, pulmonary infiltrates, and fluid retention due to the adhesion of differentiated cells to pulmonary endothelium.
Which treatment is commonly used to manage severe APL syndrome?
A) Discontinuation of ATRA and supportive care
B) Immediate high-dose chemotherapy
C) Continuous infusion of cytarabine
D) Rituximab
Answer: A) Discontinuation of ATRA and supportive care
Rationale: Severe APL syndrome may require temporary discontinuation of ATRA, glucocorticoids, cytoreduction, and supportive measures.
