2S [LEC]: Myeloproliferative Neoplasms Flashcards
Characterized by excessive proliferation of one or more mature myeloid cell lines
Myeloproliferative neoplasms
Genetic mutation most commonly associated with chronic myelogenous leukemia
BCR-ABL
Mutation implicated in polycythemia vera, primary myelofibrosis, and essential thrombocytopenia
Janus Kinase 2/ JAK2V617F (Jak2)
BCR-ABL is also referred to as ___
Philadelphia chromosome
This mutation causes the substitution of phenylalanine for valine at position 617 of the gene
JAK2V617F
Gene mutation present in BCR-ABL
t(9;22)
BCR gene is located on what chromosome?
Chromosome 22
ABL gene is located on what chromosome?
Chromosome 9
The resulting fusion protein causes increased ___ activity, which promotes cell proliferation
Tyrosine kinase
A therapeutic agent that targets the molecular defect by blocking tyrosine kinase activity
Imatinib mesylate
T/F: Patients with CML have better prognosis if they do not have the Philadelphia chromosome
False
M:E ratio of patients with CML
25:1
This CML phase is characterized as indolent
Initial (chronic) phase
This CML phase is when patients become refractive to traditional therapy and may precede acute phase
Accelerated phase
If the patient has greater than 50 x 10^9/L or reaching 500 x 10^9/ L WBC count with increased mature granulocytic forms, eosinophilia, basophilia, and thrombocytosis, it is possible that the patient has ___
CML
The LAP score of CML patients is usually ___
Decreased
CML can mimic this condition as they both display a “left” shift
Neutrophilic Leukemoid Reaction
The first synthetic tyrosine kinase inhibitor that selectively binds the ATP binding site and thus inhibit the tyrosine kinase activity of the BCR-ABL fusion protein
Imatinib mesylate
A condition related to CML where neutrophil granulocytes are present and 10% are immature, which may manifest with hepatosplenomegaly, bleeding, gout, and pruritus
Chronic Neutrophilic Leukemia (CNL)
Population predominantly affected by CML
46-53 y/o
Population predominantly affected by CNL
67 y/o
T/F: CNL affects women more than men
False (CNL affects both sexes equally)
Leukemia associated with expansion of monocytes
Chronic monocytic leukemia
Leukemia that affects children younger than 4 years of age
Juvenile Myelomonocytic Leukemia
Leukemia that presents >1.5 x 10^9/L eosinophil
Chronic eosinophilic leukemia not otherwise specific (CEL-NOS)
Proliferation of mast cells, mutation in the KIT gene
Mastocytosis
Malignant hyperplasia of the multipotent myeloid stem cell that causes an increase in all cell lines
Polycythemia vera
The most constant and striking feature of polycythemia vera is ___
Erythroid hyperplasia
Population predominantly affected by polycythemia vera
40-60 y/o, Men
Which of the following manifests in polycythemia vera?
i. RBC count of 7-10 x 10^12/L
ii. hematocrit of <60%
iii. increased hgb of >20 g/dL
i & iii (hct in PV is >60%)
Which of the following manifests in polycythemia vera?
i. high M:E ratio
ii. decreased LAP score
iii. hypocellular bone marrow
iv. increased whole blood viscosity
iv only
(PV:
normal or low M:E ratio
increased LAP score
hypercellular bone marrow)
A condition with increased RBC mass as an appropriate response to increased EPO due to tissue hypoxia
Secondary polycythemia
EPO level in polycythemia vera is ___
Decreased
A condition with decreased plasma volume with a normal RBC mass caused by dehydration or shock
Relative (pseudo) polycythemia
A 35-year old patient who was found to have renal cell carcinoma, living in Baguio City, and is a long-time smoker presents increased EPO but normal plasma volume, leukocyte count, and platelet count. What could be the possible condition of the patient?
Secondary polycythemia
Primary control of polycythemia vera
Therapeutic phlebotomy
Removal of units of whole blood or by large-volume erythrocytapheresis
Therapeutic phlebotomy
Use of alkylating myelosuppressive agents to reduce the risk of thrombosis and bleeding
Myelosuppressive therapy
Treatment with JAK inhibitors
Targeted molecular therapy (momelotinib)
Condition with systemic bone marrow fibrosis and extramedullary hematopoiesis
Primary Myelofibrosis with Myeloid Metaplasia
A condition in which the marrow is gradually replaced by fibrotic tissue
Myelofibrosis
Collagen type predominantly present in the bone marrow of patients with myelofibrosis
Collagen I, III, and IV
Reactive process that causes overproduction of collagen that eventually disrupts the normal architecture of the BM and replaces hematopoietic tissue
Myelofibrosis
Expected RBC abnormality seen on PBS of patients with myelofibrosis
Nucleated RBCs
Teardrop-shaped RBCs
If the patient has MMM, the bone marrow aspirate manifests ___, because of reticulin and collagen fibrosis being locked in the marrow content
Dry tap
A 51-year old (M) patient presents progressive anemia and enlarged spleen and liver. His CBC revealed decreased platelet count, while his PBS showed dacrocytes. What may be the possible condition of the patient?
Primary Myelofibrosis with Myeloid Metaplasia
The least common among myeloproliferative neoplasms
Essential thrombocytosis/ thrombocythemia
This condition is characterized by a significant increase in circulating platelets, usually in excess of 600 x 10^9/ L with giant forms, and platelet function abnormalities
Essential thrombocytosis/ thrombocythemia
Second peak of cases of Essential thrombocytosis/ thrombocythemia occur in women in which stage of their lives?
Childbearing age
Identify the condition:
Erythrocytes: Decreased
Leukocytes: Extremely increase
Platelets: Moderately increased
LAP: Decreased
*Positive for Ph’ chromosome
CML
Identify the condition:
Erythrocytes: Decreased
Leukocytes: Variable
Platelets: Variable
LAP: Variable
Marrow fibrosis: Very increased
*Presence of teardrop-shaped RBCs
*Increased number of NRBCs
Primary myelofibrosis
Identify the condition:
Erythrocytes: Extremely increased
Leukocytes: Increased
Platelets: Moderately increased
LAP: Extremely increased
Marrow fibrosis: None
Polycythemia vera
Identify the condition:
Erythrocytes: Normal
Leukocytes: Normal
Platelets: Extremely increased
LAP: Normal/ increased
Marrow fibrosis: None
Essential thrombocytosis
A 48-year old patient was seen with Gaucher-like macrophages. He also present enlarged spleen and liver, with normal RBC count, platelet count, and lymphocytes. Other peripheral blood parameters such as WBC count, neutrophils, basophils, and eosinophils, are increased. What could be the possible condition of the patient?
Chronic myeloid leukemia
Treatment used to quickly reduce the platelet count
Plateletpheresis
A treatment preferred with concomitant thrombocytosis and leukocytosis
Hydroxypurea
