6.4 Myeloproliferative disorders

Question 1

What cells are neoplastic in Myeloproliferative diseases?

Answer 1

Neoplastic mature cells of myeloid lineage (all of them, though one kind will generally predominate)

Question 2

Who gets Myeloproliferative diseases?

Answer 2

People in late adulthood

Average 50-60 years

Question 3

What are the myeloproliferative diseases?

Answer 3

CML, Polycythemia Vera, Essential Thrombocythemia, Myelofibrosis

Question 4

Very general features of myeloproliferative diseases

Answer 4

High WBC count, hypercellular marrow

Cells of all myeloid lineages increased

Question 5

Complications of myeloproliferative diseases

Answer 5

Increased risk of hyperuricemia and gout from high cell turnover
Progression of marrow fibrosis or transformation to acute leukemia

Question 6

What cells proliferate in CML?

Answer 6

Mature myeloid cells, especially granulocytes and their precursors
Basophils characteristically increased

Question 7

What drives CML?

Answer 7

t(9;22) Philadelphia chromosome which generates BCR-ABL fusion protein with increased tyrosine kinase activity

Question 8

What is first line treatment for CML and why?

Answer 8

Imatinib: blocks tyrosine kinase activity

Question 9

What is a common presenting sign of CML and what progression of the disease often follows?

Answer 9

Splenomegaly is common
Enlarging spleen signifies progression to an accelerated phase of the disease
Transformation to acute leukemia often follows–can be AML or ALL

Question 10

How is CML distinguished from a leukemoid reaction?

Answer 10

Negative leukocyte alkaline phosphatase stain (positive in leukemoid reaction)
Increased basophils
t(9;22)

Question 11

What is polycythemia vera?

Answer 11

neoplastic proliferation of mature myeloid cells, especially RBC’s, also includes granulocytes and platelets

Question 12

What mutation is assoc. c polycythemia vera?

Answer 12

JAK2 kinase mutation

Question 13

Hydroxyurea

Answer 13

Antineoplastic drug used for myeloproliferative diseases
Polycythemia vera, Sickle cell anemia, essential thrombocytosis
Inhibits DNA synthesis

Question 14

Sx of polycythemia vera

Answer 14

All from hyperviscosity of blood

1) Blurry vision and HA
2) Venous thrombosis
3) Flushed face from congestion
4) Itching after bathing from increased histamine release from more mast cells

Question 15

How can polycythemia vera be distinguished from reactive polycythemia?

Answer 15

PV: EPO low and SaO2 normal
RP: EPO high and SaO2 low
RP from ectopic EPO production: EPO high, SaO2 high

Question 16

Essential Thrombocythemia

Answer 16

Proliferation of mature myeloid cells, especially platelets, but includes RBC’s and granulocytes
Assoc. c JAK2 kinase mutation
SSx: increased bleeding or thrombosis
Rarely progresses to acute leukemia and no risk of gout

Question 17

Myelofibrosis

Answer 17

Proliferation of mature myeloid cells, especially megakaryocytes
Assoc. c JAK2 kinase mutation
Megakaryocytes release excess PDGF causing marrow fibrosis
Clinical: splenomegaly from extramedullary hematopoiesis, tear-drop and nucleated RBC’s on smear with immature granulocytes, increased risk of infection, thrombosis, and bleeding

Question 18

Which of the Myeloproliferative diseases have an association with JAK2kinase mutation?

Answer 18

All but CML:
Polycythemia Vera
Essential Thrombocythemia
Myelofibrosis