Myeloproliferative Disorders

Question 1

How do we characterize myeloproliferative disorders, how do we classify them, and what patient population is affected?

Answer 1

Proliferation of mature cells of the myeloid lineage. It’s important to note that there is an increase in all the types of myeloid cells, but we classify it based on the predominantly elevated one.
50-60.

Question 2

3 complications of myeloproliferative disorders?

Answer 2

Gout, marrow fibrosis, and acute leukemia

Question 3

How do we characterize Chronic Myeloid Leukemia?

Answer 3

Proliferation of mature myeloid cells, especially granulocytes and their precursors, and basophils are classically elevated.

Question 4

What is the cause of the elevation of granulocytes in CML?

Answer 4

Translocation 9:22 producing a BCR-ABL fusion protein with increased tyrosine kinase activity.

Question 5

What is first line treatment of CML and why?

Answer 5

Imatinib which is a tyrosine kinase inhibitor.

Question 6

What are the three phases of CML and how do we characterize each one?

Answer 6

Chronic phase is big spleen
The accelerated phase is marked by the spleen getting even bigger
The transformation phase is changing to acute leukemia.

Question 7

Which type of leukemia can CML transform to and what does this suggest?

Answer 7

2/3 of the time is can transform to AML and 1/3 to ALL.

This suggested that the mutation driving the disease is in the HSC so it can drive both lineages

Question 8

What do we need to distinguish CML from and what are the three ways we do it?

Answer 8

From infection because of the WBC count elevation

1. CML is LAP negative but infection is LAP positive because of the inflammatory reaction has it
2. CML has basophils, reaction to infection does not
3. T9:22 mutation is in CML not infection response

Question 9

How do we characterize Polycythemia Vera?

Answer 9

Proliferation of mature myeloid cells, especially RBCs.

Question 10

What is the mutation for PV?

Answer 10

Jak2 kinase mutation

Question 11

What are the 4 classic clinical symptoms of PV and what are the clinical symptoms due to, what is the underlying condition?

Answer 11

The viscosity of the blood has increased due to all the RBCs
Blurred vision and HA
Increased risk of clot (budd chiari syndrome)
Flushing of the face
Itching after bathing because of mast cell increase and releasing histamine

Question 12

What is first line and second line treatment of PV?

Answer 12

Phlebotomy and hydroxyurea

Question 13

What must we distinguish PV from and what are the three ways we do it?

Answer 13

Reactive polycythemia

1. In PV, EPO levels are down because of negative feedback of all the RBCs, and SaO2 is normal
2. In reactive due to high altitude or lung disease the SaO2 will be down and EPO is up to make more because we are hypoxic
3. In reactive poly due to an ectopic tumor producing EPO, renal cell carcinoma, SaO2 is normal but EPO is high,

Question 14

How do we characterize essential thrombocythemia and what is the classic mutation associated with it?

Answer 14

Proliferation of myeloid cells, especially platelets.

Jak2 kinase

Question 15

What are the two possible clinical symptoms with ET?

Answer 15

Either the increased platelets are functional so we have risk of clots or they wont be functioning and there will be bleeding

Question 16

3 rare things that happen with this disease that is noteworthy?

Answer 16

Marrow fibrosis, gout, and progression to acute leukemia

Question 17

Why is gout rare?

Answer 17

Because the platelets don’t have nucleus to turn over so we aren’t running anything through the purine degradation process resulting in uric acid.

Question 18

How do we characterize myelofibrosis and what is the associated mutation?

Answer 18

Proliferation of myeloid cells, especially megakaryoctyes.

JAK2 kinase mutation

Question 19

What is the big time problem with myelofibrosis?

Answer 19

Marrow fibrosis because the megakaryocytes produce a ton of PDGF

Question 20

What are three clinical features of myelofibrosis?

Answer 20

Big spleen because now blood cell production needs to be taken over by spleen and liver to a certain extent
Leukoerythroblastic smear
Increased infection, bleeding and clots

Question 21

What is going on with a leukoerythroblastic smear?

Answer 21

During normal blood cell production, bone marrow has reticulin gates that keep immature blood cells from leaving and entering the blood. Well, that ain’t happening when the spleen takes over, so we get immature cells in the blood.

Question 22

What kind of RBC do we also find with myelofibrosis?

Answer 22

Tear drop RBC