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MDS and PV Insights
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MDS and PV Insights
MDS and PV Insights
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1
Question
What happens to patients after treatment with Lenalidomide?
Answer
Patients become transfusion independent with normal or near-normal hemoglobin levels, but their cytogenetics also become normal.
2
Question
How is Lenalidomide administered?
Answer
Lenalidomide is administered orally.
3
Question
What are the common toxicities of Lenalidomide treatment?
Answer
Toxicities include myelosuppression worsening thrombocytopenia and neutropenia, necessitating blood count monitoring and an increased risk of deep vein thrombosis and pulmonary embolism.
4
Question
What drugs are especially effective for younger MDS patients 60 years old?
Answer
ATG, cyclosporine, and the anti-CD52 monoclonal antibody alemtuzumab.
5
Question
What is the response rate of patients with mainly refractory anemia to ATG?
Answer
About 50% of patients responded to ATG, usually combined with cyclosporine, particularly patients with hypocellular marrow.
6
Question
What are HGFs and how do they affect blood counts?
Answer
HGFs can improve blood counts but have been most beneficial to patients with the least severe pancytopenia.
7
Question
What is the effect of EPO in anemia treatment?
Answer
EPO alone or in combination with G-CSF can improve hemoglobin levels, particularly in those with low serum EPO levels who have no or a modest need for transfusions.
8
Question
What does G-CSF treatment fail to improve?
Answer
G-CSF treatment alone failed to improve survival in a controlled trial.
9
Question
What effect do thrombopoietin mimetics have in MDS patients?
Answer
Thrombopoietin mimetics appear to improve platelet counts in some MDS patients, with no clear evidence that they increase the rate of leukemic transformation.
10
Question
What is Luspatercept and what is its approval status?
Answer
Luspatercept affects transforming growth factor mediated suppression of erythropoiesis and has been approved by the FDA for anemia in MDS.
11
Question
What novel targeted therapies are in trials for MDS?
Answer
Inhibitors of hypoxia-inducible factor and spliceosome genes, drugs that act to restore TP53 activity, and venetoclax, an inhibitor of the bcl2 protein.
12
Question
What is the supportive care principle for MDS?
Answer
The same principles of supportive care described for aplastic anemia apply to MDS.
13
Question
How does myelophthisis occur and what diseases can cause it?
Answer
Myelophthisis can occur as a primary hematologic disease (myelofibrosis) or as a secondary process due to invading tumor cells or infections.
14
Question
What kind of blood smear is characteristic of myelophthisis?
Answer
A characteristic blood smear called leukoerythroblastosis.
15
Question
What are possible causes of marrow fibrosis?
Answer
Fibrosis can be a response to invading tumor cells, infections (such as Mycobacterium tuberculosis), fungi, or HIV.
16
Question
What is the pathophysiology of secondary myelofibrosis?
Answer
Three distinct features: proliferation of fibroblasts in the marrow space, extension of hematopoiesis into the long bones and extramedullary sites, and ineffective erythropoiesis.
17
Question
What is the typical erythrocyte morphology in secondary myelofibrosis?
Answer
Highly abnormal, with circulating nucleated RBCs, teardrops, and shape distortions.
18
Question
What are the clinical features of polycythemia vera (PV)?
Answer
PV is characterized by isolated thrombocytosis, leukocytosis, or splenomegaly, often recognized by a high hemoglobin or red cell count.
19
Question
What mutation is commonly associated with polycythemia vera?
Answer
A mutation in the autoinhibitory pseudokinase domain of the JAK2 tyrosine kinase, specifically V617F.
20
Question
How is the JAK2 gene linked to polycythemia vera?
Answer
JAK2 is essential for the function of erythropoietin and thrombopoietin receptors, and mutation leads to constitutive activation.
21
Question
What are the common presenting symptoms of polycythemia vera?
Answer
Neurologic symptoms such as vertigo, tinnitus, headache, visual disturbances, and transient ischemic attacks (TIAs).
22
Question
What is the significance of hepatic venous thrombosis in relation to polycythemia vera?
Answer
Hepatic venous thrombosis, especially Budd-Chiari syndrome, is particularly common in young women and may indicate the presence of JAK2 V617F.
23
Question
What complication can arise from thrombocytosis in PV?
Answer
Acquired von Willebrand disease due to absorption and proteolysis of high-molecular-weight von Willebrand multimers.
24
Question
What is the differential diagnosis for elevated hemoglobin in polycythemia vera?
Answer
It is complex due to many diagnostic possibilities, particularly if the hemoglobin level is below 20 g/dL.
25
Question
What is the World Health Organization classification of chronic myeloproliferative neoplasms?
Answer
Includes chronic myeloid leukemia, chronic neutrophilic leukemia, chronic eosinophilic leukemia, polycythemia vera, primary myelofibrosis, essential thrombocytosis, mastocytosis, and myeloproliferative neoplasms, unclassifiable.
26
Question
What is the role of phosphorylation of proteins in cellular processes?
Answer
Phosphorylation of proteins is involved in cell proliferation, differentiation, and resistance to apoptosis.
27
Question
What happens to transgenic animals lacking JAK2?
Answer
Transgenic animals lacking JAK2 die as embryos from severe anemia.
28
Question
What are the consequences of constitutive activation of JAK2 in relation to erythropoietin?
Answer
Constitutive activation of JAK2 explains erythropoietin hypersensitivity, erythropoietin-independent erythroid colony formation, rapid terminal differentiation, increased Bcl-XL expression, and apoptosis resistance in the absence of erythropoietin, characteristic of the in vitro behavior of PV erythroid progenitor cells.
29
Question
What percentage of PV patients express the JAK2 mutation?
Answer
More than 95% of PV patients express the JAK2 mutation.
30
Question
What is the significance of the JAK2 gene location?
Answer
The JAK2 gene is located on chromosome 9.