| Terms |
Definitions |
|
Retinoblastoma
(definition, 3 mechanisms, presentation)
|
- autosomally dominant, inherited cancer in which primitive retinal cells grow over retina into vitreous humor or under the retina causing detachment
- Knudson's "two-hit", LOH, spontaneous retinoblastoma
- leukocoria, strabismus, calcification
|
|
oncogene
|
mutated genes that produce an aberrant protein that stimualtes cell division, proliferation, or differentiation, even in the absence of proper growth signals.
-typically act as dominant gain-of-function mutations
|
|
glucose-6-phosphate dehydrogenase
(role in the pentose phosphate pathway, consequences of deficiency)
|
enzyme catalyzes the oxidation of glucose-6-phosphate to 6-phosphogluconolactone, NADPH are produced from this reaction
- individuals carrying the mutation are often asymptomatic until provoked by illness or exposure to certain drugs (or fava beans)
|
|
Burkitt lymphoma
(two forms, associated oncogene and virus)
|
-cancer of the jaw
- associated with MYC (cell proliferation transcription factor) translocation
- there is also a form that affects abdominal organs
- EBV implicated in etiology
|
|
How does a deficiency in the glycolytic enzyme pyruvate kinase leads to abnormalities in red blood cells?
(presentation, AEs, treatment)
|
-presents as hemolytic anemia, but there is some compensation by the fact that 2,3-BPG levels increase
-mutations in PK have been linked to increased resistance to malaria
-treatment: splenectomy and continued transfusions
|
|
What are the genes primarily affected in HNPCC aka Lynch Syndrome?
|
MLH1 and MLH 2; encode proteins that function in DNA mismatch repair
|
|
Warm antibody type of hemolytic anemia(symptoms, antibody, mechanism, causes)
|
jaundice, splenomegaly
IgG
extravascular hemolysis
SLE, drug therapies, plus common causes
|
|
What are the differences between Hodgkin's and Non-Hodgkin's lymphomas?
|
Hodgkin's arises in a single or related nodes, spreads continuously, and contain Reed-Sternberg cells.
Non-Hodgkin's arise at extranodal sites and spread in an unpredictable manner (ex Burkitt lymphoma)
|
|
What phosphorylates cyclin-Cdk pair?
|
CAK
|
|
CML
(translocation, proto-oncogene, mechanism, treatment mechanism)
|
-t(9;22)
-ABL from 9q to 22q, BCR region
-BCR/ABL results in enhanced tyrosine kinase activity
- Gleevec antibody against BCR/ABL, prevents phosphorylation of tyrosines in proteins
|
|
A patient presents to the emergency department with nausea, headache, and dizziness. On physical examination his lips and fingernail have a bluish tint. Arterial blood gas sampling reveals arterial partial oxygen pressure of 100 mm Hg and an arterial
|
methylene blue, methemoglobinemia
|
|
How does a deficiency in the glycolytic enzyme phosphofructokinase leads to abnormalities in red blood cells?
|
phosphofructokinase represents the first committed step in glycolysis
symptoms include hemolytic anemia, rhabdomyolysis and myoglobinuria, increased glycogen storage, hyperuricemia and muscle cramps with exercise
|
|
What is purpose of the glutathione cycle in RBCs?
|
protects the cell from ROS which can damage proteins and lipids
|
|
Define the enzymatic activity of biphosphoglycerate mutase.
|
required for the synthesis of 2,3 BPG from 1,3 BPG
BPG causes a right shit on a hemoglobin-oxygen saturation curve. The purpose of 2,3 BPG is to reduce the affinity of hemoglobin for oxygen such that it can be delivered to tissue sites that have an increased oxygen requirement
|
|
What are the two function of glycolysis in RBCs?
|
generate ATP
generate NADH used to reduce methemoglobin to normal hemoglobin
|
|
colorectal cancer
|
|
|
neurofibromatosis Type 1
(definition, presentation, location, mechanism
|
-autosomal dominant disease of the nervous system
- cafe-au-lait spots, Lisch nodules on the iris
- 17q11.2, LOH leads to malignancy
- NF1 is similar to a GAP protein, which inactivates RAS, a mutation to this protein leads to increased activity of RAS oncogene
|
|
What are blister cells?
|
shapes produced after a hemolytic attack in a G6PD individual
|
|
What protein inactivates cyclin D complex and is transcribed by p53?
|
p21
|
|
define the enzymatic activity of biphosphoglycerate mutase and how the product 2,3 BPG influences the affinity of hemoglobin for oxygen
|
biphosphoglycerate is required for the synthesis of 2,3 BPG
- 2,3- DPG is an allosteric effector of hemoglobin and is expressed in erythrocytes and placental cells
- it causes a right shift in the hemoglobin-oxygen saturation curve
- it reduces the affinity of hemoglobin for oxygen so oxygen is released to tissues
|
|
What kinases activate p53 and what triggers their activity?
|
ATR and ATM kinases, triggered by DNA damage
|
|
What are the two major products of the pentose phosphate pathway and what downstream pathways are they involved in?
|
- NADPH and ribose-5-phosphate
- NADPH is involved in fatt acid synthesis and glutathione reduction
- Ribose-5-nucleotide is involved in nucleotide biosynthesis
|
|
A 5-year-old girl is referred to a pediatric hematologist for an evaluation of chronic anemia that has been unresponsive to nutritional supplementation. The child has low weight and height for age; pallor; mild jaundice; spleen barely palpable; liver no
|
Pyruvate Kinase Deficiency
|
|
What four factors will decrease the percent of O2 saturation?
|
pH decrease, pCO2 increase, temperature increase, 2,3 BPG increase
|
|
What is RASs mode of action and how can a mutation lead to NF-1?
|
RAS hydrolyzes GTP to GDP inactivated Ras protein
a point mutation resulting in a constitiutively active form of Ras
--> upregulates expression of Myc-->transcription of D cyclins
|
|
What drug can cause G6PD deficiency?
|
primaquine
|
|
Discuss how the loss of APC function can lead to deregulated cell proliferation. (function, WTN involvement)
|
- APC genes main function is to downregulate growth promoting signals
-when WTN is absent, B-catenin is degraded
- when WTN is present, B-catenin is able to produce c-MYC and cyclin D1
|
|
define the role of methemoglobin reductase/ cytochrome b5 reductase in maintaining hemoglobin's affinity for oxygen, explain how the deficiency is acquired and how methemoglobinemia is treated
|
methemoglobin reductase/ cytochrome b5 reductase use NADH from glycolysis to reduce ferric hemoglobin to ferrous hemoglobin. Only ferrous hemoglobin binds oxygen.
- a genetically acquired mutant hemoglobin allele
- drugs that cause a high level of oxidation (certain antibiotics and local anaesthetics, nitrates)
- methylene blue and ascorbic acid funciton as reducing agents
|
|
How is glutathione used to protect the red blood cell from oxidative damage?
|
The cysteine residues between two glutathione molecules can form disulfide bonds and thus can be used as a site of oxidation and reduction
|
|
HER2
fucntion and mode of action
|
EGFR, overexpression, seen in 25% of breast cancers
|
|
Cold agglutinin type anemia (symptoms, mechanism of action, cause)
|
agglutinated RBCS cause occlusion
IgM
intravascular hemolysis and extravascular
infections and lymphoid neoplasms
|
|
What is the difference between NADPH and NADH as intermediates?
|
NADPH is used in anabolic reactions (cholesterol biosynthesis, fatty acid biosynthesis) while NADH is used in catabolic reactions (glycolysis and TCA cycle)
|
