6.4 Myeloproliferative Disorders (MPD)

Question 1

ET (essential thrombocythemia)

-what non-leukemia has similar symptoms?

Answer 1

-Iron deficiency anemia can also present with thrombocytopenia, like ET

Question 2

PV (polycythemia vera)

-tx (2)

Answer 2

1. phlebotomy (remove RBCs)
2. hydroxyurea (antineoplastic)

Question 3

PV (polycythemia vera)

-clinical presentation (4)

Answer 3

Symptoms mostly caused by hyperviscosity of blood

1. Headache, blurry vision
2. Increased risk of venous thrombosis (most common cause of Budd-Chiari syndrome–blockage of hepatic vein)
3. Flushed face (congestion of blood)
4. Itching, esp after bathing (classically also increased mast cells)

Question 3

You see patient with polycythemia. What is your differential, and how to differentiate?

Answer 3

1. PV:

SaO2 normal, EPO low

2. high altitude/lung disease:

SaO2 low, EPO high

3. ectopic EPO tumor (renal cell carcinoma)

SaO2 normal, EPO high

Question 3

ET (essential thrombocythemia)

-what mutation

Answer 3

-assoc with JAK2 kinase mutation

Question 3

tear drop RBCs

Answer 3

• RBCs must squeeze through fibrosis of bone marrow to enter blood
• characteristic of marrow fibrosis (myelofibrosis)

Question 5

CML (chronic myeloid leukemia)

• genetic mutation
• what precursor cell is the mutation in?

Answer 5

• t(9:22)–philadelphia chromosome.
• generates a BCR-ABL fusion protein, with increase tyrosine kinase activity (which increases cell growth)
• mutation is in the pluripotent stem cell. Therefore, increased mutations can transform CML into an AML or ALL.

Question 6

Reactive polycythemia from an ectopic EPO tumor–what is the classic tumor that does this?

Answer 6

Renal cell carcinoma

Question 7

CML (chronic myeloid leukemia)

• proliferation of what?
• increase in what cell is characteristic of CML

Answer 7

• proliferation of all mature myeloid cells, esp granulocytes
• characteristic: increase in basophils

Question 8

PV (polycythemia vera)

-proliferation of what?

Answer 8

-MPD–all mature myeloid cells, esp RBCs

Question 8

Myelofibrosis

-clinical features (3)

Answer 8

1. Splenomegaly (hematopoiesis occurs in spleen and liver b/c marrow is fibrosed)
2. leukoerythroblastic smear (tear drop RBCs, nucleated (immature) RBCs, immature granulocytes)–Spleen does not have reticulin gates like marrow to prevent release of immature cells. Also, marrow fibrosis leads to tear drop RBCs
3. increased infections, thrombosis, bleeding– spleen cannot compensate for amount of blood cell production from marrow

Question 9

Myelofibrosis

-why is there increased risk of infection, thrombosis, and bleeding?

Answer 9

• Bone marrow is fibrosed, so blood cell production is limited.
• spleen takes over hematopoiesis, but it cannot compensate

Question 10

CML (chronic myeloid leukemia)

-tx

Answer 10

-Tyrosine kinase inhibitor (Imatinib)

Question 12

PV (polycythemia vera)

-what mutation

Answer 12

-JAK2 kinase mutation

Question 13

MPD (myeloproliferative disorders)

• proliferation of what cells of what what lineage?
• how classified?

Answer 13

• in all MPDs, mature cells of all myeloid lineages are increased (RBCs, granulocytes, monocytes, platelets)
• classified by which one is predominantly increased

Question 15

How to distinguish CML from leukemoid reaction (reactive neutrophilic leukocytosis from infection/inflammation)

(3 ways)

Answer 15

1. LAP- in CML (leukocyte alkaline phosphatase stain).
   - LAP+ in inflammation, LAP- in CML
2. basophilia in CML (inflammation does not increase basophils)
3. t(9:22) only in CML

Question 16

PV (polycythemia vera)

-how to distinguish from reactive polycythemia?

Answer 16

1. PV:

SaO2 normal, EPO low

2. high altitude/lung disease:

SaO2 low, EPO high

3. ectopic EPO tumor (renal cell carcinoma)

SaO2 normal, EPO high

Question 17

Myelofibrosis

-what assoc mutation

Answer 17

-assoc with JAK2 kinase mutation (50% of cases)

Question 18

Myelofibrosis

-what do you see in blood smear

Answer 18

“Leukoerythroblastic smear”

• tear drop RBCs
• nucleated RBCs (immature)
• immature granulocytes

(spleen does not have reticulin gates like marrrow to prevent release of immature cells)

Question 19

When you see basophilia, think what?

Answer 19

CML (proliferation of all myeloid cells, esp mature granulocytes)

Question 20

CML (chronic myeloid leukemia)

-phases

Answer 20

1. chronic
2. accelerated–marked by enlarging spleen
3. transformation (to ALL or AML)–mutation is in the pluripotent stem cell

Question 22

ET (essential thrombocythemia)

1. symptoms
2. can progress to what
3. what symptom is characteristically absent, compared to other MPDs

Answer 22

1. excessive clotting or bleeding (if platelets do not work)
2. like all MPDs, can progress to acute leukemia. Also marrow fibrosis. Both rare.
3. No hyperuricemia/gout b/c platelet formation does not involve nuclear material turnover (platelets bud off from megakaryocytes)

Question 23

t(9:22) causes what leukemia

Answer 23

• CML
• philadephia chromosome. creates BCR-ABL fusion protein, with increased tyrosine kinase activity.

Question 24

MPD (myeloproliferative disorders)

-complications (2)

Answer 24

1. Hyperuricemia, gout (high turnover of cells means degradation of nuclear material, which contains purines)
2. progression to marrow fibrosis or acute leukemia (more mutations could arrest stems cells in premature form)

Question 25

Myelofibrosis

• proliferation of what?
• what is mech

Answer 25

• MPD, proliferation of megakaryocytes
• megakaryocytes produce excess PDGF, causing marrow fibrosis