Sickle Cell Anemia

Question 1

What chromosome is BCL11A on?

Answer 1

Chromosome 2

Question 2

What is the function of BCL11A

Answer 2

It is a trans acting transcriptional repressor and gamma globin silencer involved in the switch from gamma to beta globin

Question 3

What chromosome is HSBS1L-MYB on?

Answer 3

Chromosome 6

Question 4

What is the function of MYB?

Answer 4

It is a trans acting intergenic transcription factor which represses the production of gamma globin

Question 5

What is the severity of sickle cell disease in a patient who had high levels of HbF?

Answer 5

Less severe disease

Question 6

List the order of these racial haplotypes in order of severity:
     Arab-Indian and Senegal
     Cameroon
     Bantu
     Benin

Answer 6

Most severe to least severe:
    Bantu
    Benin
    Cameroon
    Arab-Indian and Senegal

Question 7

Normal level of fetal hemoglobin in blood and amount that it can be raised to

Answer 7

0.1 to 1%, but can be raised to 20%

Question 8

During ischemia, what enzyme do RBCs start to express?

Answer 8

Xanthine oxidase

Question 9

Xanthene oxidase converts

Answer 9

Oxygen to superoxide radical

Question 10

The presence of Superoxide radicals lead to inflammation and further vasooclusion and ischemia by which 4 effects?

Answer 10

1. NFkappaB expression
2. release of inflammatory cytokines
3. leukocyte activation –> RBC-leukocyte adhesion
4. Decreased NO availability (no vasodilation)

Question 11

What adhesion molecules are present on endothelial cells?

Answer 11

1. Adhere to RBCs
   - VCAM
   - Pselectin
2. Adhere to Leukocytes
   - ICAM
   - Psel
   - Esel

Question 12

What is the function of SOD1?

Answer 12

It converts superoxide to hydrogen peroxide

Question 13

What is the function of catalase

Answer 13

It converts hypdrogen peroxide to water plus oxygen

Question 14

What are the functions of GPX and PRDX2?

Answer 14

They scavenge hydrogen peroxide

Question 15

What is GSH?

Answer 15

Non-enzymatic antoxidant - damaged and dehydrated dense RBCs have very low levels

Question 16

Autoxidation of HbS leads forms what two molecules?

Answer 16

MetHbS and O2- (radical)

Question 17

H202 when in contact with MetHbS causes

Answer 17

• Release of heme and free iron

- These deposit on cytoplasmic surface of RBC membrane and catalyze the production of OH-

Question 18

If superoxide O2- binds NO what is formed?

Answer 18

RNS ONOO-

Question 19

What other cells besides RBCs produce ROS in an NADPH oxidase dependent respiratory burst in response to inflammation?

Answer 19

PMNs - neutrophils

Question 20

Why is sickle cell anemia considered in double jepoardy?

Answer 20

3x as much oxygen radicals and very low levels of enzymatic and nonenzymatic antioxidant scavengers

Question 21

Reaction of SOH with a neighboring cystein will create which two species which are reversible?

Answer 21

Disulfide and mixed disulfide–> S-glutathiolated

Question 22

Under increased oxidative stressed SOH can be further oxidized into which two species that lead to irreversible oxidative damage?

Answer 22

1. Sulfrinic Acid -SO2H

2. Sulfonic Acid - S03H

Question 23

In Sickle Cell anemia, there is reversible oxidative damage to which enzyme that allows phospholipids to go down their concentration gradient?

Answer 23

Scramblase

Question 24

Damage to scramblase causes:

Answer 24

Loss of phosphatidyl serine assymetry (Phosphatidyl serine is usually mantained on the inside) and subsequently, patches of negative charges on the outside leading to coagulation, thrombosis, and recognition by macrophages - decreased lifespan of RBC

Question 25

What is the cause of transformation from low density sickle cells to dense sickle cells?

Answer 25

Interaction of abnormal cation transport pathways, which produce cellular dehydration

Question 26

In ISCs, their beta actin contains what:

Answer 26

a disulfide bridge that cant depolymerize

Question 27

What are the four causes that leads to the transformation from dense reversible sickle cells to dense ISCs?

Answer 27

1. B-actin 2. Oxidation 3. Diminished spectrin 4. Ubiquination

Question 28

Name some future therapies that are being investigated for sickle cell anemia

Answer 28

1. effect K leakage - senicapoc -gardos channel inhibitor 2. effect NO levels and adhesion - Statins 3. Effect oxidative stress -NAC 4. Effect inflammation - lovostatin 5. Effect HbF levels - decitabine 6. Replacement of the defective gene with gene therapy

Question 29

Which biomarker in the plasma correlated with sickle cell associated pulm hypertension and acute pain episodes?

Answer 29

apolipoprotein A-1

Question 30

Which biomarker leads to low antioxidant capacity, inc ox stress, and a more severe phenoytype?

Answer 30

microRNA mir144

Question 31

How should you treat a patient with acute chest syndrome?

Answer 31

treat ALL possible causes quickly 1. antibiotics 2. oxygenation 3. Incentive spirometry 4. Possible transfusion

Question 32

What is the safest possible transplant cure for sickle cell anemia patients?

Answer 32

Harvested placental cord blood from newborn sibling

Question 33

What is the first mild chemotherapeutic treatment agent used in sickle cell anemia?

Answer 33

Hydroxyurea

Question 34

What is the only cure for sickle cell anemia?

Answer 34

Bone marrow transport with identical HLA - siblings, which is only available in 14% of families

Question 35

Which chromosome is the beta gene cluster for Hb on?

Answer 35

Chromosome 11

Question 36

Which chromosome is the alpha gene cluster for Hb on?

Answer 36

Chromosome 16