CML Module--Krafts

Question 1

CML

Polycythemia Vera

Essential Thrombocythemia

Myelofibrosis

cell predominance

Answer 1

neutrophils

RBCs

megakaryocytes

all lines–fibrosis of marrow

Question 2

What type of enzyme is normally mutated in chromic myloproliferative disorders?

Answer 2

tyrosine kinases

Question 3

What is the odd thing you see on a slide in CML?

Answer 3

basophilia

Question 4

What is the only cause of basophilia?

Answer 4

chronic myeloid leukemia

(CML)

Question 5

Basic lab findings of CML

Answer 5

• high WBC
• neutrophilia with left shift
• basophila
• anemia
• high platelets (at first)

-decreased leukocyte alkaline phosphatase (LAP)

LAP only in neutrophils

Question 6

Leukocyte alkaline phosphatase

(LAP)

Answer 6

seen only in neutrophils

decreased in malignancy

Question 7

What is the mutation in CML?

Answer 7

Philedelphia chromosome

t(9;22)

Question 8

What does the spleen do in CML?

Answer 8

extramedullary hematopoiesis

Question 9

Chronic phase CML

Answer 9

• stable counts
• easily controlled
• 3-4 years (untreated)
• becomes either accelerated phase or blast crisis

Question 10

Accelerated phase CML

Answer 10

• unstable counts
• blast crisis within 6-12 mo.
• 50% of patients with chronic phase CML

Question 11

Blast crisis

Answer 11

• acute leukemia
• high mortality
• 50% of patients from chronic phase CML

Question 12

Chronic phase

Accelerated phase

Blast crisis

in CML

Answer 12

chronic phase is stable

50% become accelerated phase

50% become blast crisis

Question 13

How can you get an acute lymphoblastic leukemia from CML?

Answer 13

blast crisis

t(9;22) occurs high up in progenitor cells

Question 14

3 types of CML remission

Answer 14

hematologic remission: nomal CBC and physical

cytogenetic remission: no t(9;22) on metaphases

molecular remission: no BCR/ABL transcripts by PCR

Question 15

Mutation in polycythemia vera

Answer 15

Jak-2 mutation

JAK = just another kinase

Question 16

EPO in polycythemia vera

Answer 16

low

problem is in progenitor cells

Question 17

Pruritis in polycythemia vera

Answer 17

due to basophils

(and that’s all we know)

Question 18

Pathway disrupted in polycythemia vera

Answer 18

JAK-STAT pathway

mutated JAK-2

constitutively activated

STAT = signal transducer and activator of transcription

Question 19

Tx of polycythemia vera

Answer 19

phelbotomy

maybe myelosuppressive drugs?

Question 20

Survival in polycythemia vera

Answer 20

9-14 years

death from hemorrhage or thrombosis

Question 21

Essential thrombocythemia odd population

Answer 21

young women (~30 y/o)

Question 22

Why do you look for the Philedelphia chromosome in thrombocythemia?

Answer 22

need to rule out CML

CML can cause high platelet counts

essential thrombocythemia is a Dx of exclusion

Question 23

Chronic myelofibrosis cell line

Answer 23

panmyelosis

all cell lines

Question 24

What type of cell is seen predominently in chronic mylofibrosis?

Answer 24

teardrop red cells

Question 25

Answer 25

chronic myelofibrosis

Question 26

Pathophys of chronic myelofibrosis

Answer 26

filling up marrow

extramedullary hematopoiesis

Question 27

Ph’

Answer 27

Philedelphia chromosome

Question 28

t(9;22) translocation makes what fusion protein?

Answer 28

BCR-ABL1 tyrosine kinase

Question 29

What drug binds BCR-ABL1 ATP binding site?

Answer 29

imatinib

Question 30

Imatinib MOA

Answer 30

selectively binds BCR-ABL1 fusion protein tyrosine kinase ATP binding site

Question 31

Function of myristate on ABL1

Answer 31

autoinhibition of ABL1 tyrosine kinase