Week 4 CML

Question 1

Wnt-b catenin

Answer 1

When activated GMP can self renewal

leads to accelerated and blast phase

Question 2

CEBPalpha

Answer 2

when inhibited, leads to differentiation block found in accelerated and blast phase

Question 3

Creation of BCR-ABL

Answer 3

abl1 from 9 swaps with segment of 22 and attaches to BCR portion of 9. makes philly chromosome
TRANSLOCATION

Question 4

BCR-ABL1 mechanism

Answer 4

Lacks myristate, leaving it in open position (active)
Coiled coil region of BCR promotes dimerization (needed for tyrosine kinase)
Result is no signal needed to activate

Question 5

Y177 in CML

Answer 5

Binds to BCR-ABL1 complex and is phosphorylated
Leads to dysregulated prolif and protection against apoptosis
Not normally activated by BCR because BCR is not tyrosine kinase

Question 6

Stat5 in CML

Answer 6

Phosphorylated without control, leads to proliferation

Question 7

Imatinib mechanism

Answer 7

Binds ATP site on bcr-abl1 complex and shuts it down.

Question 8

Cure for CML?

Answer 8

Imatinib has 85-95% response. delays death in 25% of blast crisis
bone marrow transplant only curative therpay. (cant get over age 60)

Question 9

chronic myeloid leukemia

CMPD

Answer 9

neutrophils
increase WBC. Left shift. basophilia
low hemo AND high platelet (at first)

Sx - fever fatigue and night sweats. abd fullness
signs - big spleen and liver

Question 10

polychythemia vera

CMPD

Answer 10

^RBC. Need to be from myeloid problem, not kidney
Thrombosis and hemorrhage
Jak-2 mutation (cells grown on their own). Phospho receptor, stat attaches, phospho stat, dimer goes to transcription

Sx - plethora (flushing) and big liver/spleen
Signs - headache, thrombosis, infarct

Question 11

essential thromobcythemia

CMPD

Answer 11

Platelets (can happen in young women)
thrombosis and hemorrhage
diagnose by ruling everything else out and platelet over 600K

sx: bleeding and thrombosis
signs: bruising, pallor, large spleen, tachycardic

Question 12

myelofibrosis

CMPD chronic myeloproliferative disorder

Answer 12

Everything prolif! Panyelosis and eventually marrow fibrosis
extramedullary hematopoiesis and tear drop cells

Sx: LUQ fullness, weakness, fatigue, heat arrythmia
signs: large spleen/liver and pallor, tachycardia

Question 13

treatment for polychythemia vera

Answer 13

phlebotomy. maybe suppressive drugs

9-14 years average but die form thrombosis or hemorrhage

Question 14

treatment for essential thrombocythemia

Answer 14

platelet pheresis, suppressive drugs and aspirin

5-8 years, but die from thrombosis or hemorrhage

Question 15

treatment for myelofibrosis

Answer 15

supportive

3-5years but die from marrow failure

Question 16

clinical problems from myeloma

Answer 16

Severe anemia
Acute renal failure
epigastric distress
weight loss

Question 17

multiple myeloma must know:

Answer 17

monoclonal plasma cell prolif and gammopathy
decreased immunoglobulin
osteolytic lesions

Question 18

Multiple myeloma labs:

Answer 18

M spike
Bence Jones prtein in urine (light chain Ig)
Low Ig
Blood: anemia and rouleaux
bone marrow: plasma cells and amyloid

Question 19

Clincal triad of MM

Answer 19

bone pain, anemia and renal failure