Week 4 CML Flashcards Preview

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Flashcards in Week 4 CML Deck (19):
1

Wnt-b catenin

When activated GMP can self renewal
leads to accelerated and blast phase

2

CEBPalpha

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

3

Creation of BCR-ABL

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

4

BCR-ABL1 mechanism

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

5

Y177 in CML

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

6

Stat5 in CML

Phosphorylated without control, leads to proliferation

7

Imatinib mechanism

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

8

Cure for CML?

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

9

chronic myeloid leukemia
CMPD

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

10

polychythemia vera
CMPD

^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

11

essential thromobcythemia
CMPD

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

12

myelofibrosis
CMPD chronic myeloproliferative disorder

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

13

treatment for polychythemia vera

phlebotomy. maybe suppressive drugs
9-14 years average but die form thrombosis or hemorrhage

14

treatment for essential thrombocythemia

platelet pheresis, suppressive drugs and aspirin
5-8 years, but die from thrombosis or hemorrhage

15

treatment for myelofibrosis

supportive
3-5years but die from marrow failure

16

clinical problems from myeloma

Severe anemia
Acute renal failure
epigastric distress
weight loss

17

multiple myeloma must know:

monoclonal plasma cell prolif and gammopathy
decreased immunoglobulin
osteolytic lesions

18

Multiple myeloma labs:

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

19

Clincal triad of MM

bone pain, anemia and renal failure