Myeloproliferative Neoplasms

Question 1

Overproduction of RBCs

Answer 1

Primary defect of Polycythemia vera

Question 2

Overproduction of granulocytes

Answer 2

Primary defect of chronic myelocytic leukemia

Question 3

Overproduction of platelets

Answer 3

Primary defect of Essential Thrombocytosis

Question 4

Overproduction of bone marrow fibroblasts

Answer 4

Primary defect of Primary Myelofibrosis

Question 5

Can exhibit hypereosinophilia and/or hyperbasophilia

Answer 5

myeloproliferative neoplasms (MPNs)

Question 6

Best known mutation is in the gene for a protein called JAK2 (>90%)

Answer 6

Polycythemia vera

Question 7

All cells appear normal
RBCs function normally and have normal lifespan

Answer 7

Polycythemia Vera (PV)

Question 8

Stem cells with JAK2 mutation are resistant to erythropoietin apoptosis

Answer 8

Polycythemia Vera (PV)

Question 9

• Hgb level
• Identification of JAK2 mutation

Answer 9

Major criteria of PV
(both need to be met)

Question 10

1. Panmyelosis in bone marrow
2. Low serum EPO level
3. Autonomous, erythroid colony formation

Answer 10

Minor criterion of PV (only 1 needs to be met)

Question 11

18.5 g/dL in men
16.5 g/dL in women

Answer 11

PV Hgb levels for major criteria

Question 12

Low EPO levels

Answer 12

PV lab findings

Question 13

Anemia
Fever
Excessive bleeding or bruising
Malaise
Hepatosplenomegaly

Answer 13

CML Clinical Symptoms

Question 14

• Causes extreme elevation of both mature & immature myeloid cells in bone marrow which then shows up in the p.b.
• Slow clinical course
• Primarily seen in adults, but can occur at any age

Answer 14

CML

Question 15

> 95% patients are Philadelphia (Ph’) chromosome +

Answer 15

CML Cytogenetics

Question 16

BCR/ABL fusion protein

Answer 16

CML Cytogenetics

Question 17

When the p.b. Looks like bone marrow!

Answer 17

CML lab findings

Question 18

P.b. shows a huge left shift with all developmental stages!

Answer 18

CML lab findings

Question 19

> 20% basophilia heralds an impending blast crisis

Answer 19

CML lab findings

Question 20

• chronic phase
• accelerated phase
• blastic phase

Answer 20

Three phases of CML

Question 21

• Usually occurs prior to blastic phase
• Poor response to therapies
• Increase in symptoms and lab values

Answer 21

Accelerated phase of CML

Question 22

• About ¾ CML patients undergo “blast transformation” from chronic into acute phase
• Increased blast count to >20%
• Becomes either AML, or more rarely, ALL

Answer 22

Blastic phase of CML

Question 23

________ binds directly to the BCR/ABL fusion protein/tyrosine kinase produced by Ph’

Answer 23

Gleevec

Question 24

And eventually no more abnormal, Ph translocation-containing cells can be found = _____ ______

Answer 24

Molecular Remission - Treatment with Gleevec

Question 25

It cures > 88% of patients in chronic phase (with variable results in other phases)

Answer 25

Treatment with Gleevec

Question 26

Clonal stem cell disorder (Associated w/ JAK2 mutation- 65% of patients)

Answer 26

Primary Myelofibrosis (PMF)

Question 27

Aka. Chronic Idiopathic Myelofibrosis (CIMF) and myelofibrosis with myeloid metaplasia, MMM

Answer 27

Primary Myelofibrosis (PMF)

Question 28

Dry tap due to varying degrees of bone marrow fibrosis

Answer 28

Primary Myelofibrosis (PMF)

Question 29

Patients usually die from 2 most common complications of bone marrow failure ?

Answer 29

Overwhelming infections & massive hemorrhage -- Primary Myelofibrosis

Question 30

Clonal stem cell disorder (associated with JAK2 mutation) Causes extremely ↑ platelet count

Answer 30

Essential Thrombocythemia

Question 31

Platelet function is abnormal unless numbers ↓ by plateletpheresis – this differentiates ET from what leukemia?

Answer 31

AML M7 – AMegL

Question 32

- Platelet count ~600,000- 2,500,00/uL - Giant bizarre plts., but not megakaryocyte fragments in p.b. - Slt. leukocytosis with neutrophilia - Abnormal plt. Aggregation studies

Answer 32

Essential Thrombocythemia

Question 33

- Positive Giant Platelets - NO nRBCs - Slight left shift - No megakaryocyte fragments

Answer 33

Essential Thrombocythemia

Question 34

- Positive Giant Platelets - Positive nRBCs - Rare left shift - Positive megakaryocyte fragements

Answer 34

M7 (AMegL)