Myeloproliferative Neoplasms

Question 1

What are the major differences between myelodysplastic and myeloproliferatiive conditions?

Answer 1

Myeloprolierative neoplasms are quantitative abnormalities only, while myelodysplastic syndromes are quantitative and qualitative disorders. Myelodysplastic syndromes manifest as cytopenia and myeloproliferative neoplasms manifest as cytosis. There is ineffective hematopoiesis in myelodysplastic syndromes and minimal organomegaly

Question 2

What are myeloproliferative neoplasms characterized by?

Answer 2

Proliferation of one or more myeloid lineages

Question 3

Describe the marrow of myeloproliferative neoplasms

Answer 3

Hypercellular

Question 4

What is the diagnosis for a myeloproliferative neoplasms positive for BCR-Abl 1?

Answer 4

Chronic Myelogenous Leukemia

Question 5

What myeloproliferative neoplasms are Bcr-Abl 1 negative?

Answer 5

Polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic eosinophilic leukemia, and mastocytosis

Question 6

What cytogenetic abnormality is associated with chronic myelogenous leukemia?

Answer 6

t(9;22)(q34;q11)

Question 7

What is the most common myeloproliferative neoplasm?

Answer 7

CML

Question 8

What abnormal findings would be seen in the peripheral blood smear of a pt with CML?

Answer 8

Absolute granulocytosis, tendancy toward left shift, basophilia

Question 9

How can a leukemoid reaction be distinguished from CML?

Answer 9

Leukemoid reactions have WBC counts that typically don’t exceed 30K, while CML counts are greater than 50K; CML will also have basophilia and nRBCs present

Question 10

What are the phases of CML? What is the worst?

Answer 10

Chronic Phase, Accelerated phase, and Blast phase (worst case)

Question 11

What is the mechanism of Gleevec’s action?

Answer 11

Gleevec fits into the normal ATP binding site on BCR-Abl to prevent phosphorylation of the tyrosine kinase

Question 12

What are the different types of responses used to access efficacy of tyrosine kinases inhibitors

Answer 12

Hematologic response, cytogenetic response, molecular response

Question 13

True or False: Myelofibrosis is specific to primary myelofibrosis.

Answer 13

False

Question 14

What are different phases and bone marrow findings of non BCRAbl Myeloproliferative Neoplasms?

Answer 14

Cellular phase (hypercellularity); Spent/fibrotic phase (progressive fibrosis replacing hematopoietic cells); leukemic phase (increased blasts)

Question 15

What induces myelofibrosis?

Answer 15

Induced by release of cytokines and growth factors, PDGF, TGF-B

Question 16

What is JAK2?

Answer 16

A tyrosine kinase that plays an important role in normal hematopoietic growth factor signalling

Question 17

Mutation in JAK2 is most highly correlated with what myeloproliferative neoplasm?

Answer 17

Polycythemia vera

Question 18

Mutations in what protein is the cause of many BCRAbl -, JAK2 mutation negative myeloproliferative neoplasms?

Answer 18

CALReticulin

Question 19

Are mutations in JAK2 of CALR associated with a poorer prognosis?

Answer 19

CALR

Question 20

What is the primary problem in polycythemia vera?

Answer 20

Increased RBC production

Question 21

True or False: patients with polycythemia vera have very low EPO levels.

Answer 21

True

Question 22

The increased blood viscosity that results in polycythemia vera predisposes pts to what kinds of problems?

Answer 22

Thrombotic and hemorrhagic

Question 23

What are the major symptoms and lab findings associated with polycythemia vera?

Answer 23

Gout, Erythomelalgia, Splenomegaly, High Hb/HCT, Increased RBC mass, JAK2+ mutation

Question 24

What are the different stages of Polycythemia vera?

Answer 24

Polycythemic stage, Post-polycythemic (spent) stage;

Question 25

What are the causes of secondary polycythemia?

Answer 25

Chronic pulmonary/ cardiac disease; high oxygen affinity hemoglobinopathy, increased carboxyhemoglobin and methemoglobin, residence at high altitude, adrenal cortical hypersecretion, hydronephrosis, EPO producing tumors

Question 26

What are the most common causes of relative polycythemia?

Answer 26

Decreased plasma volume (severe dehydration) due to diarrhea, emesis, or renal diseases

Question 27

How can polycythemia vera be distinguished from secondary polycythemia?

Answer 27

Secondary polycythemia will normally not have splenomegaly, leukocytosis, thrombocytosis, or JAK2 mutations.

Question 28

What is the clinical presentation of primary myelofibrosis?

Answer 28

Nonspecific B symptoms, +/- bleeding, Hepatosplenomegaly; leukoerythroblastosis, anemia with prominent poikilocytosis and teardrop cells, large/bizzare platelets, micromegakaryocytes, nRBCs and megakaryocyte nuclei; Osteosclerosis

Question 29

What are the two phases of primary myelofibrosis?

Answer 29

Prefibrotic phase and fibrotic phase

Question 30

What are the major three criteria for diagnosing PMF?

Answer 30

1. Proliferation of abnormal megakaryocytes within reticulin and/ or collagen fibrosis in bone marrow 2. Doensn’t meet WHO criteria for CML, PV, MDS, or other myeloid neoplasms 3. Demonstration of JAK2 V617F mutation or other clonal marker OR in absence of clonal marker, no evidence of reactive marrow fibrosis

Question 31

What myeloid lineage is primarily involved in essential thrombocythemia?

Answer 31

Megakaryocytic lineage

Question 32

What is the hallmark of essential thrombocythemia on PBS?

Answer 32

Sustained Thrombocytosis

Question 33

What abnormal features can be seen in the bone marrow of a patient with essential thrombocythemia?

Answer 33

Megakaryocytic hyperplasia with abnormal, deeply lobulated (‘staghorn’) nuclei

Question 34

What is the hallmark finding of chronic eosinophilic leukemia? What is the cause of this finding?

Answer 34

Restrictive cardiomyopathy; Secondary to endomyocardial fibrosis caused by increased circulating cytokines

Question 35

What is the hallmark finding of a bone marrow biopsy of Chronic eosinophilic leukemia?

Answer 35

Eosinophilia

Question 36

What is mastocytosis? What is the etiology?

Answer 36

Clonal, neoplastic proliferation of mast cells that accumulate in one or more organ systems; Due to somatic mutations in KIT proto-oncogene

Question 37

What are the two major subsets of Mastocytosis?

Answer 37

Cutaneous Mastocytosis and Systemic mastocytosis

Question 38

What are the clinical findings associated with cutaneous mastocytosis?

Answer 38

Darier’s sign (light stroking of skin causing urticaria); Urticaria pigmentosa (pigmented cutaneous lesions)

Question 39

What diagnosis is associated with high serum tryptase?

Answer 39

Systemic mastocytosis