PV AND MYELOPROLIFERATIVE NEOPLASMS Flashcards
What is the most common mutation associated with Polycythemia Vera (PV)?
A) CALR mutation
B) JAK2 V617F mutation
C) LNK mutation
D) Exon 12 mutation in JAK2
Answer: B) JAK2 V617F mutation
Rationale: More than 95% of PV patients express the JAK2 V617F mutation.
The JAK2 V617F mutation leads to:
A) Constitutive activation of tyrosine kinase
B) Loss of erythropoietin sensitivity
C) Decreased Bcl-XL expression
D) Impaired erythroid differentiation
Answer: A) Constitutive activation of tyrosine kinase
Rationale: The JAK2 V617F mutation causes constitutive activation of the tyrosine kinase, leading to erythropoietin hypersensitivity and other PV characteristics.
Which mutation is more commonly associated with isolated erythrocytosis in PV patients?
A) JAK2 V617F heterozygosity
B) Exon 12 mutation in JAK2
C) CALR mutation
D) LNK mutation
Answer: B) Exon 12 mutation in JAK2
Rationale: PV patients with exon 12 mutations of JAK2 often present with isolated erythrocytosis.
Which of the following is NOT true regarding JAK2 V617F?
A) It is present in ~50% of PMF and ET patients.
B) It is the initiating lesion in PV.
C) It leads to increased inflammatory cytokine production.
D) It cannot fully explain the PV phenotype.
Answer: B) It is the initiating lesion in PV.
Rationale: JAK2 V617F is central to PV pathogenesis but is not the initiating lesion in PV or other MPNs.
Which of the following is a distinguishing symptom of PV compared to other causes of erythrocytosis?
A) Tinnitus
B) Systolic hypertension
C) Aquagenic pruritus
D) Transient ischemic attacks (TIAs)
Answer: C) Aquagenic pruritus
Rationale: Aquagenic pruritus, or itching triggered by contact with water, is a characteristic symptom of PV
Which of the following types of thrombosis is most commonly associated with PV in young women?
A) Cerebral vein thrombosis
B) Hepatic vein thrombosis (Budd-Chiari syndrome)
C) Coronary artery thrombosis
D) Deep vein thrombosis
Answer: B) Hepatic vein thrombosis (Budd-Chiari syndrome)
Rationale: Budd-Chiari syndrome is particularly common in young women with PV and is strongly linked to JAK2 V617F mutation.
Which complication of PV is directly associated with thrombocytosis?
A) Epistaxis
B) Erythromelalgia
C) Gastrointestinal hemorrhage
D) All of the above
Answer: D) All of the above
Rationale: Thrombocytosis in PV can cause bleeding (e.g., epistaxis and GI hemorrhage) due to acquired von Willebrand’s disease and symptoms like erythromelalgia due to increased platelet stickiness.
Erythromelalgia is characterized by:
A) Intense itching after exposure to water
B) Erythema, burning, and pain in the extremities
C) Digital necrosis from arterial thrombosis
D) Hyperuricemia and secondary gout
Answer: B) Erythema, burning, and pain in the extremities
Rationale: Erythromelalgia is a symptom of thrombocytosis in PV and involves erythema, burning, and pain in the extremities.
Which symptom is associated with the large turnover of hematopoietic cells in PV?
A) Hyperuricemia
B) Epistaxis
C) Hepatic vein thrombosis
D) Digital ischemia
Answer: A) Hyperuricemia
Rationale: The large turnover of hematopoietic cells in PV results in hyperuricemia, which may cause secondary gout and uric acid stones.
What is the primary method to reduce hyperviscosity in PV?
A) Hydroxyurea
B) Phlebotomy
C) Salicylates
D) Ruxolitinib
Answer: B) Phlebotomy
Rationale: Phlebotomy reduces the red cell mass and expands plasma volume to address hyperviscosity.
Which statement is TRUE regarding thrombosis in PV?
A) Thrombocytosis strongly correlates with thrombosis.
B) Anticoagulation is only indicated in the presence of thrombosis.
C) Salicylates are universally recommended in PV.
D) Maintaining leukocyte counts reduces thrombosis risk.
Answer: B) Anticoagulation is only indicated in the presence of thrombosis.
Rationale: Anticoagulation is used in cases of thrombosis, but salicylates and leukocyte reduction are not standard for preventing thrombosis.
What is the treatment for acquired von Willebrand’s disease due to thrombocytosis in PV?
A) Phlebotomy
B) Tranexamic acid or ε-aminocaproic acid
C) Allopurinol
D) Pegylated interferon α
Answer: B) Tranexamic acid or ε-aminocaproic acid
Rationale: These agents address bleeding caused by acquired von Willebrand’s disease due to high platelet counts.
Which drug is preferred over hydroxyurea for reducing platelet counts due to its lack of marrow toxicity?
A) Anagrelide
B) Ruxolitinib
C) Pegylated interferon α
D) Salicylates
Answer: A) Anagrelide
Rationale: Anagrelide reduces platelet counts without causing marrow toxicity and is effective against venous thrombosis.
In PV patients with massive splenomegaly and myelofibrosis, which treatment is most effective for reducing spleen size?
A) Hydroxyurea
B) Pegylated interferon α
C) Ruxolitinib
D) Alkylating agents
Answer: C) Ruxolitinib
Rationale: Ruxolitinib, a JAK2 inhibitor, reduces spleen size and alleviates symptoms associated with myelofibrosis.
Why should the use of hydroxyurea in PV be constrained?
A) It is ineffective in controlling erythrocytosis.
B) It increases the risk of leukemic transformation.
C) It worsens thrombocytosis.
D) It is associated with severe gastrointestinal side effects.
Answer: B) It increases the risk of leukemic transformation.
Rationale: Hydroxyurea antagonizes TP53 and causes del17p, increasing the risk of leukemic transformation.
What is the hallmark blood smear finding in PMF?
A) Hypersegmented neutrophils
B) Target cells
C) Teardrop-shaped red cells
D) Heinz bodies
Answer: C) Teardrop-shaped red cells
Rationale: Teardrop-shaped red cells are characteristic of extramedullary hematopoiesis in PMF.
What is the primary cause of splenomegaly in PMF?
A) Splenic infarction
B) Extramedullary hematopoiesis
C) Immune complex deposition
D) Portal vein thrombosis
Answer: B) Extramedullary hematopoiesis
Rationale: Splenomegaly in PMF results from extramedullary hematopoiesis, a hallmark feature of the disease.
Which feature on a bone marrow biopsy is typical of PMF?
A) Hypercellular marrow with trilineage hyperplasia and megakaryocyte clusters
B) Complete absence of hematopoietic elements
C) Lymphoid hyperplasia
D) Characteristic morphology distinguishing PMF from other MPNs
Answer: A) Hypercellular marrow with trilineage hyperplasia and megakaryocyte clusters
Rationale: PMF bone marrow shows hypercellularity with megakaryocyte clusters, though these findings are not unique to PMF.
Which complication is associated with exuberant extramedullary hematopoiesis in PMF?
A) Splenic infarction
B) Portal hypertension
C) Pulmonary hypertension
D) All of the above
Answer: D) All of the above
Rationale: Exuberant extramedullary hematopoiesis in PMF can cause various complications, including splenic infarction, portal hypertension, and pulmonary hypertension.
Which cytogenetic finding in PMF indicates a poor prognosis?
A) Normal karyotype
B) CALR type 1 mutation
C) Complex karyotype abnormalities
D) JAK2 V617F mutation
Answer: C) Complex karyotype abnormalities
Rationale: Complex karyotype abnormalities are associated with poor prognosis in PMF.
What is the most effective therapy for reducing splenomegaly and alleviating constitutional symptoms in advanced PMF?
A) Pegylated IFN-α
B) Ruxolitinib
C) Splenic irradiation
D) Erythropoietin
Answer: B) Ruxolitinib
Rationale: The JAK2 inhibitor ruxolitinib has shown efficacy in reducing splenomegaly and improving constitutional symptoms in most patients with advanced PMF.
Which of the following treatments is considered curative for PMF?
A) Pegylated IFN-α
B) Ruxolitinib
C) Allogeneic bone marrow transplantation
D) Fedratinib
Answer: C) Allogeneic bone marrow transplantation
Rationale: Allogeneic bone marrow transplantation is the only curative treatment for PMF and is typically reserved for younger or high-risk patients.
What is a common side effect of ruxolitinib therapy in PMF?
A) Hyperuricemia
B) Anemia and thrombocytopenia
C) Leukocytosis and thrombocytosis
D) Increased risk of splenic infarction
Answer: B) Anemia and thrombocytopenia
Rationale: Anemia and thrombocytopenia are common side effects of ruxolitinib, though these effects are dose-dependent and often stabilize over time.
Which tyrosine kinase inhibitor has been found useful in patients with PMF refractory to ruxolitinib?
A) Sorafenib
B) Fedratinib
C) Imatinib
D) Dasatinib
Answer: B) Fedratinib
Rationale: Fedratinib, with anti-FLT3 activity, is effective in managing PMF cases refractory to ruxolitinib.
What is a significant risk associated with splenectomy in PMF patients?
A) Increased anemia
B) Splenic infarction
C) Risk of blastic transformation
D) Portal hypertension
Answer: C) Risk of blastic transformation
Rationale: Splenectomy in PMF is associated with complications such as mesenteric venous thrombosis, rebound cytoses, and an increased risk of blastic transformation.
What factor limits the effectiveness of erythropoietin in treating anemia in PMF?
A) Folate deficiency
B) Serum erythropoietin levels >125 mU/L
C) Autoimmune hemolysis
D) Splenic sequestration
Answer: B) Serum erythropoietin levels >125 mU/L
Rationale: Erythropoietin therapy is ineffective when serum erythropoietin levels exceed 125 mU/L and may worsen splenomegaly.
Which mutations are most commonly associated with essential thrombocythemia (ET)?
A) BCR-ABL translocation
B) JAK2 V617F, CALR, and MPL mutations
C) p53 mutation and chromosomal deletions
D) IDH1 and IDH2 mutations
Answer: B) JAK2 V617F, CALR, and MPL mutations
Rationale: Approximately 50% of ET patients have JAK2 V617F mutations, 30% have CALR mutations, and 8% have MPL mutations.
Which of the following is a common clinical presentation of ET?
A) Severe anemia
B) Splenomegaly with significant hepatomegaly
C) Incidentally detected elevated platelet count
D) Frequent bacterial infections
Answer: C) Incidentally detected elevated platelet count
Rationale: ET is most often identified incidentally during routine medical evaluations due to elevated platelet counts.
What laboratory feature would most likely indicate a diagnosis other than ET?
A) Platelet count >1,000,000/μL
B) Increased marrow megakaryocyte hyperplasia
C) Presence of ringed sideroblasts and anemia
D) Prolonged bleeding time
Answer: C) Presence of ringed sideroblasts and anemia
Rationale: Ringed sideroblasts and anemia are features of myelodysplastic syndromes, not ET.
What is a potential complication of very high platelet counts in ET?
A) Increased risk of thrombotic events
B) Hyperkalemia causing cardiac arrhythmias
C) Hemorrhage due to acquired von Willebrand disease
D) Splenomegaly
Answer: C) Hemorrhage due to acquired von Willebrand disease
Rationale: Very high platelet counts in ET can cause acquired von Willebrand disease, leading to bleeding complications.
Which symptom is most likely to respond to platelet cyclooxygenase-1 inhibitors such as aspirin?
A) Erythromelalgia
B) Migraine-related neurological issues
C) Splenomegaly
D) Severe hemorrhage
Answer: A) Erythromelalgia
Rationale: Erythromelalgia in ET responds well to platelet cyclooxygenase-1 inhibitors like aspirin or ibuprofen.
Which of the following findings is not characteristic of ET?
A) Normal prothrombin and partial thromboplastin times
B) Large, hypertrophic megakaryocytes on bone marrow biopsy
C) Significant anemia
D) Hyperkalemia as a test tube artifact
Answer: C) Significant anemia
Rationale: Anemia is uncommon in ET and suggests an alternative diagnosis.
What is the first step in managing an asymptomatic patient with elevated platelet counts but no cardiovascular risk factors or tobacco use?
A) Start low-dose aspirin therapy
B) No therapy is needed
C) Initiate hydroxyurea therapy
D) Perform plateletpheresis
Answer: B) No therapy is needed
Rationale: An elevated platelet count in asymptomatic patients without cardiovascular risk factors or tobacco use does not require treatment.
What test can confirm acquired von Willebrand’s disease in ET patients with platelet counts >1 × 10⁶/μL?
A) Platelet aggregation test
B) Ristocetin cofactor activity test
C) Prothrombin time (PT)
D) Partial thromboplastin time (PTT)
Answer: B) Ristocetin cofactor activity test
Rationale: A reduction in ristocetin cofactor activity indicates loss of high-molecular-weight von Willebrand multimers, confirming acquired von Willebrand’s disease.
Which therapy is most effective for managing bleeding caused by acquired von Willebrand’s disease in ET?
A) Plateletpheresis
B) Hydroxyurea
C) Tranexamic acid or ε-aminocaproic acid
D) Anagrelide
Answer: C) Tranexamic acid or ε-aminocaproic acid
Rationale: These agents can be used prophylactically before and after surgery to manage bleeding.
Which statement is true regarding the evolution of ET into acute leukemia?
A) It is primarily due to the natural progression of the disease
B) It is associated with the presence of CALR mutations
C) It is more likely a consequence of therapy
D) It occurs equally with all treatment modalities
Answer: C) It is more likely a consequence of therapy
Rationale: The evolution of ET to acute leukemia is often related to treatment with agents like alkylating agents or 32P.
