CML Flashcards
Which statement best describes the function of the BCR/ABL1 fusion protein in CML?
A) It disrupts differentiation of erythroid cells.
B) It increases DNA repair in myeloid cells.
C) It activates tyrosine kinase signaling, driving unregulated cell growth.
D) It inactivates apoptotic pathways in stromal cells.
Answer: C) It activates tyrosine kinase signaling, driving unregulated cell growth.
Rationale: The BCR/ABL1 fusion protein results in constitutive tyrosine kinase activity, leading to uncontrolled proliferation of leukemic cells.
What is another name for the t(9;22) translocation in CML?
A) Philadelphia chromosome
B) PML-RARA translocation
C) RUNX1 translocation
D) Monosomy 7
Answer: A) Philadelphia chromosome
Rationale: The t(9;22) translocation is also referred to as the Philadelphia chromosome.
What is the key therapeutic target in patients with CML?
A) ABL1
B) BCR/ABL1 fusion protein
C) TP53
D) JAK2
Answer: B) BCR/ABL1 fusion protein
Rationale: Targeting the tyrosine kinase activity of the BCR/ABL1 fusion protein is the cornerstone of therapy in CML.
What is the chromosomal abnormality characteristic of classical chronic myeloid leukemia (CML)?
A) t(8;21)
B) t(9;22)
C) t(15;17)
D) inv(16)
Answer: B) t(9;22)
Rationale: The t(9;22)(q34.1;q11.2) translocation, also known as the Philadelphia chromosome, is characteristic of classical CML.
What is the most common phase of CML at the time of diagnosis?
A) Blast phase
B) Accelerated phase
C) Chronic phase
D) Myeloid transformation phase
Answer: C) Chronic phase
Rationale: The majority of CML patients (90%) present in the chronic phase, which is typically indolent.
What is the most common physical finding in patients with CML?
A) Hepatomegaly
B) Lymphadenopathy
C) Splenomegaly
D) Subcutaneous skin lesions
Answer: C) Splenomegaly
Rationale: Splenomegaly is observed in 20–70% of patients with CML and is the most common physical finding.
Which of the following findings suggests transformation of CML?
A) Hepatomegaly
B) Severe splenomegaly
C) Extramedullary disease with biopsy-confirmed blast predominance
D) Chronic fatigue
Answer: C) Extramedullary disease with biopsy-confirmed blast predominance
Rationale: Transformation of CML is indicated by the presence of extramedullary disease with predominance of blasts.
Which of the following is a characteristic finding in untreated CML?
A) Severe thrombocytopenia
B) Marked leukocytosis with left-shifted hematopoiesis
C) Lymphoid hyperplasia in the bone marrow
D) Low levels of vitamin B12 and lactic dehydrogenase
Answer: B) Marked leukocytosis with left-shifted hematopoiesis
Rationale: In untreated CML, leukocytosis (ranging from 10–500 × 10⁹/L) with a predominance of neutrophils, bands, myelocytes, and blasts (usually ≤5%) is common.
What is the typical percentage of marrow blasts in chronic-phase CML?
A) <5%
B) 5–10%
C) 10–15%
D) ≥15%
Answer: A) <5%
Rationale: In untreated chronic-phase CML, marrow blasts are typically ≤5%. Higher percentages indicate a worse prognosis or transformation to an accelerated phase.
Which of the following is a criterion for diagnosing accelerated-phase CML?
A) 10% peripheral blasts
B) 15% peripheral blasts
C) 5% peripheral basophils
D) Thrombocytosis unrelated to therapy
Answer: B) 15% peripheral blasts
Rationale: Accelerated-phase CML is defined by the presence of 15% or more blasts in the peripheral blood.
What is the definition of blastic-phase CML?
A) ≥15% blasts in peripheral blood or bone marrow
B) ≥20% blasts in peripheral blood or bone marrow
C) ≥30% blasts in peripheral blood or bone marrow
D) ≥30% blasts plus promyelocytes in peripheral blood
Answer: C) ≥30% blasts in peripheral blood or bone marrow
Rationale: Blastic-phase CML is defined by ≥30% blasts in the peripheral blood or bone marrow, or the presence of sheets of blasts in extramedullary disease.
What is the most common lineage of blasts in blastic-phase CML?
A) Lymphoid
B) Myeloid
C) Monocytic
D) Erythroid
Answer: B) Myeloid
Rationale: Blastic-phase CML is most commonly of myeloid lineage (60%), though it can occasionally present as lymphoid, monocytic, erythroid, or megakaryocytic.
Which of the following drugs is approved for use in all phases of Chronic Myeloid Leukemia (CML)?
A. Imatinib (Gleevec)
B. Nilotinib (Tasigna)
C. Ponatinib (Iclusig)
D. Omacetaxine (Synribo)
Correct Answer: A. Imatinib (Gleevec)
Rationale: Imatinib is approved for all phases of CML. While other drugs like Dasatinib and Bosutinib are also approved for all phases, Nilotinib excludes blast-phase CML, and Ponatinib is optimal only in cases of specific mutations or resistance to other therapies.
Which of the following drugs is associated with a risk of arteriovenous-occlusive disease and hypertension?
A. Imatinib (Gleevec)
B. Ponatinib (Iclusig)
C. Bosutinib (Bosulif)
D. Omacetaxine (Synribo)
Correct Answer: B. Ponatinib (Iclusig)
Rationale: Ponatinib is noted for causing significant side effects like arteriovenous-occlusive disease (10–20%) and systemic hypertension (10–15%), which makes close monitoring critical.
Which medication is recommended for patients who have failed at least two tyrosine kinase inhibitors (TKIs)?
A. Dasatinib (Sprycel)
B. Omacetaxine (Synribo)
C. Imatinib (Gleevec)
D. Bosutinib (Bosulif)
Correct Answer: B. Omacetaxine (Synribo)
Rationale: Omacetaxine is specifically indicated for patients who have failed treatment with two or more TKIs, providing an alternative when resistance or intolerance occurs.
What is a common toxicity associated with Nilotinib (Tasigna)?
A. Pleural effusions
B. Myelosuppression
C. Diabetes and arteriovenous disease
D. Diarrhea
Correct Answer: C. Diabetes and arteriovenous disease
Rationale: Nilotinib has notable toxicities, including diabetes, arteriovenous disease, and pancreatitis, distinguishing it from other drugs in this class.
