Myeloproliferative disorders- P

Question 1

What is a myeloproliferative disorder?

Answer 1

Neoplastic proliferation of mature cells of myeloid linage

- age of onset 50-60

Question 2

In Myeloproliferative disorder what happens to the bone marrow and white count?

Answer 2

Increased WBC

Hypercellular BM

Question 3

What are some complications of myeloproliferative disorders?

Answer 3

1. Increased Risk of hyperuricemia and gout due to high turn over a cells
2. Progression of marrow fibrosis and transformation of acute leukemia

Question 4

How would high cell turn over lead to hyperuricemia?

Answer 4

Degradation of Purines found in the nucleus of cells leads to increased uric acid in the blood

Question 5

What is one high yield characteristic of CML?

Answer 5

Basophilia

Question 6

What is the definition of CML?

Answer 6

Neoplastic proliferation of mature myeloid cells

- especially granulocytes and precursors

Question 7

CML is driven by a translocation. What is it? how is it treated?

Answer 7

Philadelphia chromosome translation of 9 and 22

• Generated fusion between BCR-ABL which increase tyrosine kinase activity
• treated with TKI- Imatinib

Question 8

What are the 3 phases of CML? How are they characterized?

Answer 8

1. Chronic- splenomegaly
2. Accelerated- enlarging spleen and phase 3 to follow shortly
3. Transformation- acute leukemia

Question 9

CML can transform into?

Answer 9

AML- 66%

ALL- 33%

Question 10

CML needs to be distinguished from leukemoid reaction. How can one do this?

Answer 10

1. Negative leukocyte alkaline phosphatase (LAP) stain in CML. Where the granulocytes in the leukemoid reaction need the LAP to fight infection. Neoplastic cells in CML do not.
2. Increased basophils in CML
3. 9–> 22 translocation in CML

Question 11

What is Polycythemia Vera (PV)?

Answer 11

Neoplastic proliferation of mature myeloid cells

• especially RBC’s
• granulocytes and platelets also increased

Question 12

What mutation is ass. with PV?

Answer 12

JAK 2 mutation

Question 13

What are the clinical sx’s ass. with PV and why is this so?

Answer 13

Hyper-viscosity of Blood causes:

1. Blurry vision and HA
2. Increased risk of venous thrombosis
3. Plethora
4. Itching, especially after bath/shower due to histamine release

Question 14

How would one go about treating PV?

Answer 14

Phlebotomy

• 2’ line treatment is hydroxyurea
• without treatment- death occurs in about 1 year

Question 15

What is reactive polycythemia?

Answer 15

increased in cells for a reactive reason
- ex. you need more RBC’s because you have COPD and you traveled to Denver for the week. Thus you body will push out more EPO to make more RBC’s to be more efficient at getting O2 to your tissues

FYI- can be any cells

Question 16

How does one distinguish between PV and reactive polycythemia and Renal Cell Carcinoma?

Answer 16

RCC- SaO2- Normal, EPO high (due to ectopic epo production)
PV- SaO2- Normal, EPO Low
RP- SaO2- Low, EPO high

Question 17

What is Essential thrombocythemia (ET)?

Answer 17

Neoplastic proliferation of mature myeloid cells

- especially platelets

Question 18

What mutation is ET ass. with?

Answer 18

JAK2 kinase mutation

Question 19

What are the sx’s related to in ET?

Answer 19

Bleeding and thrombosis depending on the action of the platelets (non-functioning and overactive, respectively)

Question 20

Can ET turn into a Acute leukemia or marrow fibrosis?

Answer 20

Rarely

- No significant risk of gout or hyperuricemia

Question 21

Why doesnt ET create gout via hyperuricemia?

Answer 21

Because Platelets are made from Megakaryocytes. They are basically blebs off of the MK cells cytoplasm. No Nucleus to degrade to create these sx’s.

Question 22

What is myelofibrosis?

Answer 22

Neoplastic proliferation of mature myeloid cells

- especially megakarycytes

Question 23

In 50% of the cases which mutation is myelofibrosis ass. with?

Answer 23

JAK2 kinase mutation

Question 24

What do factor does megakaryocytes produce that cause marrow fibrosis?

Answer 24

Platelet-derived growth factors (PDGF)

Question 25

What are the clinical features of myelofibrosis?

Answer 25

1. splenomegaly
2. Leukoerythroblastic smear- tear drop RBC’s, Nucleated RBC’s and blasts granulocytes
3. Increased risk for infection bleeding and thrombosis

Question 26

How does myelofibrosis cause splenomegaly?

Answer 26

As the marrow becomes more fibrotic it can no longer do its job of hematopoiesis. Thus the body takes over and turns back the clock resorting in the spleen and liver for hematopoiesis as it did as a fetus.