CH6 - 4) Myeloproliferative Disorders

Question 1

What are myeloproliferative disorders?

Answer 1

Neoplastic proliferation of mature cells of myeloid lineage; disease of late adulthood (average age is 50-60 years)

Question 2

What does myeloproliferative disorders result in?

Answer 2

high WBC count with hypercellular bone marrow

Question 3

How are myeloproliferative disorders characterized?

Answer 3

Cells of all myeloid lineages are increased; classified based on the dominant myeloid cell produced

Question 4

What are the complications for myeloproliferative disorders?

Answer 4

1) Increased risk for hyperuricemia and gout due to high turnover of cells 2) Progression to marrow fibrosis or transformation to acute leukemia

Question 5

What is chronic myeloid leukemia?

Answer 5

Neoplastic proliferation of mature myeloid cells, especially granulocytes and their precursors;

Question 6

In chronic myeloid leukemia what are characteristically increased?

Answer 6

basophils

Question 7

What is chronic myeloid leukemia driven by?

Answer 7

driven by t(9:22) - Philadelphia chromosome - which generates a BCR-ABL fusion protein with increased tyrosine kinase activity

Question 8

What is the first line treatment for chronic myeloid leukemia?

Answer 8

imatinib,

Question 9

What does imatinib do?

Answer 9

It blocks tyrosine kinase activity

Question 10

How is splenomegaly related to chronic myeloid leukemia?

Answer 10

Splenomegaly is common, enlarging spleen suggests accelerated phase of disease;

Question 11

In chronic myeloid leukemia what usually follows after splenomegaly?

Answer 11

transformation to acute leukemia

Question 12

What can chronic myeloid leukemia transform to?

Answer 12

AML in 2/3 of cases or ALL in 1/3 of cases since mutation is in a pluripotent stem cell,

Question 13

What is a leukemoid reaction?

Answer 13

Reactive neutrophilic leukocytosis

Question 14

How is CML distinguished from a leukemoid reaction (reactive neutrophilic leukocytosis)?

Answer 14

Negative LAP stain, inc basophils, t(9;22)

Question 15

What is a LAP stain?

Answer 15

leukocyte alkaline phosphatase (LAP) stain

Question 16

How is a LAP stain related to a leukemoid reaction?

Answer 16

granulocytes in a leukemoid reaction are LAP positive

Question 17

Why are basophils useful in determining the difference between a leukemoid reaction and CML?

Answer 17

Basophils are increased in CML and are absent with a leukemoid reaction

Question 18

How is t(9;22) useful in determining the difference between a leukemoid reaction and CML?

Answer 18

It is present in CML and absent in leukemoid reaction

Question 19

What is polycythemia vera?

Answer 19

Neoplastic proliferation of mature myeloid cells, especially RBCs

Question 20

In polycythemia vera, in addition to the RBC increase what are also increased?

Answer 20

Granulocytes and platelets are also increased

Question 21

What mutation is associated with polycythemia vera?

Answer 21

JAK2 kinase mutation

Question 22

What are the clinical symptoms for polycythemia vera due to?

Answer 22

they are mostly due to hyperviscosity of blood

Question 23

What are the clinical symptoms for polycythemia vera?

Answer 23

1. Blurry vision and headache 2. Increased risk of venous thrombosis (e.g., hepatic vein, portal vein, and dural sinus) 3. Flushed face due to congestion (plethora) 4. Itching, especially after bathing (due to histamine release from increased mast cells)

Question 24

What is plethora in relation to PV?

Answer 24

One of the clinical symptoms; flushed face due to congestion

Question 25

Why is there itching in PV?

Answer 25

Itching, especially after bathing due to histamine release from increased mast cells

Question 26

What is the treatment for PV?

Answer 26

phlebotomy;

Question 27

What is the second-line therapy for PV?

Answer 27

hydroxyurea.

Question 28

What happens to a patient with PV who goes intreated?

Answer 28

Without treatment, death usually occurs within one year.

Question 29

How can PV be distinguished from reactive polycythemia?

Answer 29

1. In PV, erythropoietin (EPO) levels are decreased, and Sao, is normal. 2. In reactive polycythemia due to high altitude or lung disease, SaO2 is low, and EPO is increased. 3. In reactive polycythemia due to ectopic EPO production from renal cell carcinoma, EPO is high, and Sao2 is normal.

Question 30

What are the EPO and SaO2 levels in PV?

Answer 30

EPO is decreased and SaO2 is normal

Question 31

What are the EPO and SaO2 levels in reactive polycythemia due to high altitude or lung disease?

Answer 31

EPO is increased and SaO2 is low

Question 32

What are the EPO and SaO2 levels in reactive polycythemia due to renal cell carcinoma?

Answer 32

EPO is high, SaO2 is normal

Question 33

What is essential thrombocythemia?

Answer 33

Neoplastic proliferation of mature myeloid cells, especially platelets

Question 34

In ET, in addition to the platelets what else is increased?

Answer 34

RBCs and granulocytes are also increased.

Question 35

What is mutation is ET associated with?

Answer 35

JAK2 kinase mutation

Question 36

What do the symptoms of ET result from?

Answer 36

they are related to an increased risk of bleeding and/or thrombosis.

Question 37

What do the symptoms of ET rarely progresses to?

Answer 37

marrow fibrosis or acute leukemia

Question 38

In ET what is there no significant risk for?

Answer 38

hyperuricemia or gout

Question 39

What is myelofibrosis?

Answer 39

It is neoplastic proliferation of mature myeloid cells, especially megakaryocytes

Question 40

What mutation is associated with myelofibrosis?

Answer 40

JAK2 kinase mutation in 50% of cases

Question 41

In myelofibrosis, what causes marrow fibrosis?

Answer 41

Megakaryocytes produce excess platelet-derived growth factor (PDGF) causing marrow fibrosis

Question 42

What are the clinical features for myelofibrosis?

Answer 42

1) splenomegaly 2) leukoerythroblastic smear 3) Increased risk of infection, thrombosis, and bleeding

Question 43

In myelofibrosis what is splenomegaly due to?

Answer 43

extramedullary hematopoiesis

Question 44

In myelofibrosis what is the leukoerythroblastic smear?

Answer 44

It’s tear-drop RBCs, nucleated RBCs, and immature granulocytes

Question 45

In myelofibrosis what is their an increased risk for?

Answer 45

increased risk for infection, thrombosis, and bleeding