Myeloproliferative Disorders

Question 1

3 types of myeloid neoplasms

Answer 1

1. AML
2. Myelodysplastic syndrome
3. Myeloproliferative disorders

Question 2

is characterized by blasts that replace bone marrow & suppress normal hematopoiesis.

Answer 2

AML

(myeloproliferative disorders are tumors that increase myeloid elements, ex: CML)

Question 3

CML is a myeloproliferative disorders where myeloid tumors increase _____.

Answer 3

myeloid elements

Question 4

In myeloid neoplasms, what are 2 factors that determine the type of disease (AML, myelodysplastic, or myeloproliferative)

Answer 4

1. Hierarchical position of transformed cell (stem cell or further down lineage)
2. effect of transforming event on differentiation

Question 5

4 myeloproliferative disorders

Answer 5

1. CML
2. Polycythemia vera
3. Essential thrombocytosis
4. Primary myelofibrosis

Question 6

Mutation in CML? Consequence?

Answer 6

1. BCR-ABL fusion gene
2. ABL kinase activation

Question 7

Which 3 myeloproliferative disorders have a JAK2 point mutation (consequence = JAK2 kinase activation)?

Answer 7

1. Polycythemia vera
2. Essential thrombocythemia
3. Primary myelofibrosis

(Or MPL point mutations → MPL kinase activation)

Question 8

Mutation in Systemic Mastocytosis? Consequence?

Answer 8

KIT point mutation → KIT kinase activation

Question 9

Mutation in Chronic eosinophilic leukemia? Consequence?

Answer 9

FIP1L1-PDGFRA fusion gene → PDGFRa kinase activation

Question 10

Mutation in Stem cell leukemia? Consequence?

Answer 10

FGFR1 fusion gene → FGFR1 kinase activation

Question 11

BCR-ABL (Philadelphia chromosome) is the cause of _______ (disease)

Answer 11

CML

(short chromosome 22)

Question 12

In CML, constitutive activation of BCR-ABL → activation of which pathways (2)?

Answer 12

1. RAS
2. JAK-STAT

(leads to proliferation of granulocytic & megakaryocytic precursors → immature granulocytes in blood (bands))

Question 13

Which myeloproliferative disorder is dx w/PCR or chromosome analysis?

Answer 13

CML

Question 14

Which Myeloproliferative disorder has leukocytosis, blasts, and anemia

Answer 14

CML

Question 15

CML typically affects which age group? Polycythemia Vera? Primary myelofibrosis?

Answer 15

• 50-60s
• Late middle age
• >60

Question 16

CML is a neoplastic proliferation of myeloid precursors which would normally go on to become ______ (3).

Answer 16

1. monocyte
2. erythrocyte
3. megakaryocyte

Question 17

CML symptoms (3)

Answer 17

1. splenomegaly (“dragging” sensation)
2. weakness
3. weight loss

(primary myelofibrosis also has splenomegaly)

Question 18

______ exposure is a risk factor of CML

Answer 18

benzene

Question 19

Which myeloproliferative disorders are treated with tyrosine kinase inhibitors and which are treated with phlebotomy?

Answer 19

TKI: all but polycythemia vera, which is treated with phlebotomy

Question 20

Imatinib is a tyrosine kinase inhibitor that targets _______ protein.

Answer 20

BCR-ABL

(possible resistance mutation: T315l)

Question 21

Goal of therapy w/Imatinib

Answer 21

1. complete hematological response after 3 months
2. complete cytogenic response after 6 months

(possible resistance if the mutation is T315I)

Question 22

Panmyelosis, increased Hct and HTN indicates which myeloproliferative disorder?

Answer 22

Polycythemia vera

(panmyelosis = RBCs, granulocytes & platelets)

Question 23

Polycythemia vera: sx (3)

Answer 23

1. cyanosis (due to hyperoxygenation)
2. bleeding
3. thrombotic episodes

Question 24

Essential thrombocytosis: sx (3)

Answer 24

dysfunctional platelets (thrombosis & hemorrhage)

(NO myelofibrosis (marrow fibrosis) or polycythemia vera (lack of panmyelosis)

Question 25

Which myeloproliferative disorders has a very high lab value of platelets?

Answer 25

essential thrombocytosis

Question 26

Primary myelofibrosis: sx (2)

Answer 26

1. anemia
2. splenomegaly (due to extramedullary hematopoiesis)

Question 27

Early Primary Myelofibrosis labs will show _______ (2). Late? Very late?

Answer 27

• Leukocytosis & thrombocytosis
• Hypocellular & fibrotic marrow
• osteosclerosis

Question 28

Which myeloproliferative disease is characterized by teardrop shaped RBCs (aka Dacrocytes) & nucleated RBCs on blood smear?

Answer 28

Primary myelofibrosis

Question 29

Answer 29

Question 30

Answer 30

Question 31

Answer 31

Question 32

Answer 32

Question 33

Answer 33