Myeloproliferative Disorders

Question 1

Answer 1

ET

Question 2

Answer 2

Myelofibrosis (tear drop cells, monolobed PMNs)

Question 3

Two most common leukemias

Answer 3

CLL (most common) and AML

Question 4

Answer 4

PV (Absence of iron is a typical finding in the marrow at diagnosis. Iron stores have been depleted to sustain the expanded erythrocyte mass.)

Question 5

Answer 5

CML (many different lineages)

Question 6

Basophilia is common in which myeloproliferative disorders?

Answer 6

CML, myelofibrosis, PV

Question 7

Elevated or low in CML:

Uric acid

LAP

B12

Transcobalamine

Answer 7

Uric acid - elevated (tumor lysis syndrome)

LAP - low (myelocytes are non-functional = not producing alk phos)

B12 - elevated

Transcobalamine - elevated (B12 binding protein)

Question 8

Median duration CML:

Chronic phase

Accelerated phase

Blast phase

Answer 8

Chronic phase - 5-6 years

Accelerated phase - 6-9 mo

Blast phase - 3-6 mo

Question 9

Who discovered Philadelphia chromosome?

Answer 9

Janet Rowley

Question 10

What % of patients with CML have t(9:22)?

Answer 10

95%

Question 11

What % of cells express t(9:22) in person with CML with that cytogenetic abnormality?

Answer 11

100% (of RBC, WBC, monocytes, platelets)

Question 12

Only cure for CML

Answer 12

HSCT

Question 13

Why are busulfan and hydroxyurea not that great?

Answer 13

Can’t control CML once it’s in accelerated phase

Question 14

Targeted tx for CML. MOA?

Answer 14

Imatinib - binds in ATP binding pocket of tyrosine kinase, inhibiting it

Question 15

How long must patient be on imatinib before almost all peripheral blood is back to normal?

Answer 15

~1 month!!

Question 16

More efficacious: IFN or imatinib?

Answer 16

Imatinib (much more so)

Question 17

Resistance to imatinib mediated by what mutation?

Answer 17

T-3151

Question 18

Pathway beginning with EPO binding EPO-R

Answer 18

Jak-2 activated –> STAT/PI3K/AKT/MAPK –> RBC precursor proliferation and differentiation

Question 19

Jak-2 inhibitors are effective against which diseases?

Answer 19

PV, ET, myelofibrosis

Question 20

Jak-2 mutation is most common in which of these: PV, ET, myelofibrosis

Answer 20

PT (90-95%)

Question 21

Homozygous Jak-2 mutation indicative of:

Question 22

Pt presents with bone pain, portal HTN, muscle wasting, SOB, palpitations. Lab shows thrombocytosis, leukocytosis.

Answer 22

Myelofibrosis

Question 23

Two major causes of death for myelofibrosis pts

Answer 23

Vascular disease (~35%), acute leukemia (~25%)

Question 24

Two causes of secondary thrombocytosis

Answer 24

Refractory thrombocytosis (after BM suppression)

Splenectomy

Question 25

Least common MPD

Answer 25

ET

Question 26

Secondary vs ET

Answer 26

2ndary = ELEVATED TPO, no splenomegaly, platelet function and morphology is normal, megs are normal ET = NORMAL TPO, 40% splenomegaly, megs abnormal

Question 27

Aortic and mitral valvular leaflet thickening or vegetations

Question 28

3 risk factors for thrombosis

Answer 28

1. Phx 2. Advanced age 3. CV risk factors (i.e. smoking)

Question 29

What is Budd-Chiari syndrome and which heme disorder associated with it?

Answer 29

Occlusion of hepatic vein ET

Question 30

Why can ET cause spontaneous abortion/premature deliveries/etc

Answer 30

Thrombotic complications causing placental insufficiency

Question 31

Two Rx specifically mentioned for ET

Answer 31

Hydroxyurea (ribonucleotide reductase inhibitor) Anagrelide

Question 32

MOA: Anagrelide AE?

Answer 32

Inhibits differentiation of megs = fewer platelets CHF, HA, thrombocytopenia

Question 33

Altitude sickness

Answer 33

Reactive polycythemia

Question 34

Causes of reactive polycythemia

Answer 34

\*\*Anything that would increase EPO Altitude sickness Atrial septal defect Renal hypoxia (due to artery ligation, tumor, hydronephrosis) Tumor (hypernephroma)

Question 35

Most common symptom of PV

Answer 35

HA

Question 36

Blurred vision would be most associated with which MPD?

Answer 36

PV (causes distention of retinal vessels)

Question 37

Elevated or low in PV: LAP B12 Iron stores

Answer 37

LAP - high (hyperfunctional cells) B12 - high Iron stores - low

Question 38

Raynaud phenomenon

Answer 38

PV

Question 39

TOC for PV

Answer 39

Phlebotomy (myelosuppressive Rx given when platelet/WBC count rises or when pruritic)

Question 40

Cross country runner presents with headache, bleeding, and cyanosis. Dx?

Answer 40

Reactive polycythemia due to volume depletion