Term
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Definition
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 |
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Term
Burkitt lymphoma
(two forms, associated oncogene and virus) |
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Definition
-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 |
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Term
CML
(translocation, proto-oncogene, mechanism, treatment mechanism) |
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Definition
-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 |
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Term
| What are the differences between Hodgkin's and Non-Hodgkin's lymphomas? |
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Definition
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) |
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Term
Retinoblastoma
(definition, 3 mechanisms, presentation) |
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Definition
- 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 |
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Term
neurofibromatosis Type 1
(definition, presentation, location, mechanism |
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Definition
-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 |
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Term
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Definition
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Term
| Discuss how the loss of APC function can lead to deregulated cell proliferation. (function, WTN involvement) |
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Definition
- 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 |
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Term
| What are the two major products of the pentose phosphate pathway and what downstream pathways are they involved in? |
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Definition
- NADPH and ribose-5-phosphate
- NADPH is involved in fatt acid synthesis and glutathione reduction
- Ribose-5-nucleotide is involved in nucleotide biosynthesis |
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Term
| What is the difference between NADPH and NADH as intermediates? |
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Definition
| NADPH is used in anabolic reactions (cholesterol biosynthesis, fatty acid biosynthesis) while NADH is used in catabolic reactions (glycolysis and TCA cycle) |
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Term
glucose-6-phosphate dehydrogenase
(role in the pentose phosphate pathway, consequences of deficiency) |
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Definition
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) |
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Term
| How is glutathione used to protect the red blood cell from oxidative damage? |
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Definition
| The cysteine residues between two glutathione molecules can form disulfide bonds and thus can be used as a site of oxidation and reduction |
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Term
How does a deficiency in the glycolytic enzyme pyruvate kinase leads to abnormalities in red blood cells?
(presentation, AEs, treatment) |
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Definition
-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 |
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Term
| How does a deficiency in the glycolytic enzyme phosphofructokinase leads to abnormalities in red blood cells? |
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Definition
phosphofructokinase represents the first committed step in glycolysis
symptoms include hemolytic anemia, rhabdomyolysis and myoglobinuria, increased glycogen storage, hyperuricemia and muscle cramps with exercise |
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Term
| 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 |
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Definition
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 |
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Term
| define the enzymatic activity of biphosphoglycerate mutase and how the product 2,3 BPG influences the affinity of hemoglobin for oxygen |
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Definition
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 |
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Term
| What are the two function of glycolysis in RBCs? |
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Definition
generate ATP
generate NADH used to reduce methemoglobin to normal hemoglobin |
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Term
| What is purpose of the glutathione cycle in RBCs? |
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Definition
| protects the cell from ROS which can damage proteins and lipids |
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Term
| What four factors will decrease the percent of O2 saturation? |
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Definition
| pH decrease, pCO2 increase, temperature increase, 2,3 BPG increase |
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Term
HER2
fucntion and mode of action |
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Definition
| EGFR, overexpression, seen in 25% of breast cancers |
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Term
| What is RASs mode of action and how can a mutation lead to NF-1? |
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Definition
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 |
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Term
| What phosphorylates cyclin-Cdk pair? |
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Definition
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Term
| What kinases activate p53 and what triggers their activity? |
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Definition
| ATR and ATM kinases, triggered by DNA damage |
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Term
| What protein inactivates cyclin D complex and is transcribed by p53? |
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Definition
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Term
| What are the genes primarily affected in HNPCC aka Lynch Syndrome? |
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Definition
| MLH1 and MLH 2; encode proteins that function in DNA mismatch repair |
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Term
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Definition
| shapes produced after a hemolytic attack in a G6PD individual |
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Term
| Define the enzymatic activity of biphosphoglycerate mutase. |
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Definition
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 |
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Term
| 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 partial carbon dioxide pressure of 40 mm Hg. The nurse who drew blood for the gas analysis notes that the patient’s blood for the gas analysis notes that the patient’s blood looked oddly brown in the collecting tube. Which of the following is the most appropriate treatment for this condition? |
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Definition
| methylene blue, methemoglobinemia |
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Term
| 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 not enlarged. Additional findings include anemia with a markedly increased reticulocyte count, macro-ovalocytosis with a few acanthocytes, no sickle cells or spherocytes but hyper-bilirubinemia (primarily unconjugated). Which of the following disorders is most likely the cause of the child’s poor health? |
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Definition
| Pyruvate Kinase Deficiency |
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Term
| What drug can cause G6PD deficiency? |
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Definition
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Term
| Warm antibody type of hemolytic anemia(symptoms, antibody, mechanism, causes) |
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Definition
jaundice, splenomegaly
IgG
extravascular hemolysis
SLE, drug therapies, plus common causes |
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Term
| Cold agglutinin type anemia (symptoms, mechanism of action, cause) |
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Definition
agglutinated RBCS cause occlusion
IgM
intravascular hemolysis and extravascular
infections and lymphoid neoplasms |
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