Cancer, Blood

Question 0

Benign vs. Malignant

Answer 0

Benign: well demarcated, noninvasive, well differentiated, slow growing, usually encapsulated masses
Malignant: poorly demarcated, locally invasive, metastatic, poorly differentiated, rapidly growing with hemorrhage and necrosis, anaplasia

Question 1

Hyperplasia vs. Dysplasia vs. Anaplasia

Answer 1

Hyperplasia: increase number of normal cells
Dysplasia: some cellular changes leading to abnormal tissue
Anaplasia: undifferentiated cells, vary in size and shape, atypical mitoses, disorganized tissue

Question 2

What are proto-oncogenes?

Answer 2

Proto-oncogenes encode proteins that stimulate cell proliferation

Question 3

How do proto-oncogenes become altered? What will happen with RAS mutations?

Answer 3

When altered, they become “oncogenes” from change in genome (dominant)
Overexpression of autocrine growth factors
Mutated forms of receptors with constitutive activity
RAS mutations: If GTP doesn’t hydrolyze to GDP, then it will continue to activate intercellular signals (RAF and MAPK) that tell the cell to grow (high in colon and pancreatic cancers)

Question 4

What is RAS?

Answer 4

Encodes p21 G protein which transmits mitogenic signal from activated GF receptors, then phosphorylation cascade of other transducing proteins to the nucleus
When RAS is mutated (colon and pancreatic CA), it continues to signal to grow more proto-oncogenes

Question 5

What do CDKs normally do? What if they become altered?

Answer 5

Proto-oncogenes stimulate expression of CDKs which are growth related genes that drive the progression of the cell cycle
Dysregulation of CDK/mutations promote proliferation, most commonly affecting proteins in G1-S transition

Question 6

What are tumor suppressor genes? When cancer cells mutate/truncate/delete/methylate, how can uncontrolled growth occur (do they activate or inactivate these genes)?

Answer 6

Tumor suppressor genes encode proteins that normally inhibit cell proliferation or stimulate apoptosis when a cell is damaged
When they are INACTIVATED in cancer cells, uncontrolled growth can occur. Genetically, his occurs with two alleles affected (recessive).
**So uncontrolled proliferation comes from increasing proto-oncogene activity or inactivating tumor suppressor cells

Question 7

What is p53?

Answer 7

p53 is the “guardian of the genome”, a tetrameric transcription factor protein which binds to a DNA sequence of genes encoding proteins responsible for cell cycle arrest and apoptosis, it is a tumor suppressor gene. It detects cellular stress and prevents propagation of damaged cells

Question 8

Under normal conditions, when there is cellular stress, p53 is released from the complex with MDM2 (MDM2 will increase half-life and activate transcription factor activity). p53 activates a CDK inhibitor, p21, this will ______ (turn on/off?) the cell cycle which will activate DNA repair systems (GADD45)

Answer 8

Turn OFF the cell cycle
Upon cellular stress, the p53 will help by activating CDK inhibitor to make the cell go through apoptosis. If this didn’t occur, mutated and damaged cells would be propagated
Note: over 70% of cancers involve p53 mutation

Question 9

Differentiate between the three types of p53 mutations: loss of function, gain of function, dominant negative mutant

Answer 9

Loss of function: mutant p53 is not functional, but does not interfere with actions of the allele
Gain of function: mutant p53 binds to different DNA sequences and activates target genes, stimulating cell proliferation
Dominant negative mutant: mutant p53 forms a complex with the allele and prevents its binding to the target gene promoters, therefore not allowing it to do its normal job which is apoptosis and cell proliferation continues

Question 10

Can DNA repair genes facilitate mutations in oncogenes and tumor suppressors?

Answer 10

Yes, even though DNA repair genes aren’t directly involved in the cell cycle, when cancerous/mutated, they can impact cell cycle regulation by facilitating mutations in oncogenes/ tumor suppressor cells

Question 11

What is the function of BRCA1 and BRCA2? What cancers are they correlated with when mutated?

Answer 11

BRCA1 and BRCA2 encode nuclear proteins involved in response to DNA damage and DNA repair
BRCA1 with germline mutation is associated with breast and ovarian cancers, also with families with multiple breast cancer cases
BRCA2 with germline mutations is associated with breast cancer, NOT ovarian cancer, also male breast cancer

Question 12

True or false: Deregulation of apoptosis leads to propagation of damaged, mutated cells.

Answer 12

True

Question 13

What is telomerase? When is senescence?

Answer 13

Telomerase is an enzyme, which in stem cells maintain normal telomere length preventing senescence. Senescence is menopause for cells, the telomere length is too short and can’t replicate anymore.
(Everytime we go through mitosis, telomere length shortens)

Question 14

What happens when telomerase is upregulated?

Answer 14

Upregulated telomerase activity would allow unlimited cell divisions

Question 15

What is angiogenesis? How does it relate to tumor growth?

Answer 15

The growth of capillary blood vessels. Angiogenesis is necessary for exponential tumor growth and metastasis, the perfusion prevents apoptosis (p53 pathway)

Question 16

What is a way that tumor cells can invade and metastasize?

Answer 16

They can invade the extracellular matrix by altering cell-cell adhesion molecules, increase activity of matrix degrading enzymes (metalloproteinases), and migrate through the matrix by autocrine motility factors (stimulated by chemoattractants growth factors)

Question 17

How can cancer cells evade the host immunity response?

Answer 17

They can invade so that healthy cells can’t recognize foreign antigens, specifically, invading MHC-1 can create this problem

Question 18

How do genotoxic vs. non-genotoxic carcinogens work?

Answer 18

Genotoxic carcinogens interact with DNA causing replication errors and mutations
Non-genotoxic carcinogens change expression of genes

Question 19

How can viruses contribute to cancer development?

Answer 19

DNA viruses can synthesize proteins inactivating human genes in cell cycle control (HPV), express proteins stimulating cell proliferation (EBV, HBV), or tissue injury leading to the induction of regeneration processes (HBV)
Ex: HPV inactivates p53

Question 20

What are cytokine induced symptoms of cancer?

Answer 20

Pain, wasting, fatigue, cognitive changes, anxiety, depression, GI disturbances

Question 21

What are some side effects and longterm effects from chemo and radiation therapy?

Answer 21

Side effects: Hair loss, GI dysfunction, mouth sores, skin reaction, bone marrow depletion of immune cells and erythrocytes
Long term: infertility, secondary cancers, osteoporosis, growth abnormalities

Question 22

Between anemia, hypoxia, and polycythemia vera; which increases erythropoietin production in the kidney in response to decreased RBC mass and which decreases erythropoietin in response to increased RBC mass?

Answer 22

Anemia and hypoxia increase erythropoietin in response to decreased RBC
Polycythemia vera decreases erythropoietin in response to increased RBC

Question 23

What is anemia? What can cause it?

Answer 23

Decrease in total number (10%) of erythrocytes in the blood or quality/quantity of hemoglobin
Due to impaired erythrocyte production, acute/chronic blood loss, or increased erythrocyte destruction
“cytic”-size/shape, “chromic”-Hgb content
MCV, MCH, MCHC look at quality

Question 24

What is Macrocytic-normochromic anemia? What is an example?

Answer 24

Characterized by a large stem cell (megaloblast) in the bone marrow that matures into larger erythrocytes making them “macrocytic” (large cell bodies). Hemoglobin content is normal = normochromic
Stems from defective erythrocyte precursor DNA synthesis. RNA synthesize is NORMAL, so the cells have a disproportional small nucleus with a huge body
For example, deficiencies in vitamin B12/folate which are coenzymes for DNA synthesis causes pernicious anemia

Question 25

What is Pernicious Anemia? What is it caused by?

Answer 25

A macrocytic normochromic anemia caused by lack of IF from gastric parietal cells
IF helps with vitamin B12 absorption, so this creates the vitamin B12 deficiency
Caused by autoimmune, gastric bypass, or congenital

Question 26

Pernicious Anemia: symptoms, what does gastric biopsy reveal, and treatment?

Answer 26

Symptoms: slow onset, nerve demyelination (bc neurons aren’t getting enough oxygen), other s/s of anemia (weakness, loss of appetite)
Gastric biopsy can reveal achlorhydria (absence of hydrochloric acid) which is normally secreted by gastric parietal cells
Treatment is Vitamin B12 replacement

Question 27

What are microcytic-hypochromic anemias?

Answer 27

RBCs are abnormally small and contain reduced hemoglobin. This is related to iron metabolism (iron deficient anemia), porphyrin and heme synthesis, and globin synthesis

Question 28

Iron deficiency anemia: Symptoms and treatment

Answer 28

Symptoms: s/s of anemia plus brittle thin spoon-shaped nails, and red sore tongue, low hemoglobin and low ferritin
Treatment: ferrous

Question 29

What is sideroblastic anemia?

Answer 29

A hypochromic anemia (can be microcytic or macrocytic) characterized by a deviation in mitochondrial metabolism which alters iron uptake, leads to dysfunction heme synthesis in the bone marrow

Question 30

Sideroblastic anemia: symptoms, diagnosis, and treatment

Answer 30

Symptoms: increased tissue levels of iron, splenomegaly, hepatomegaly
Diagnosis: ringed sideroblasts in the bone marrow
Treatment: pyridoxine therapy (corrects heme synthesis, in heme biosynthesis pathway)

Question 31

What is Thalassemia?

Answer 31

A microcytic-hypochromic anemia in which there is increased hemolysis (RBC destruction) resulting in decrease RBC. This is associated with globin chain synthesis, can be alpha or beta

Question 32

Thalassemia treatment

Answer 32

Blood transfusions, splenectomy, chelation therapy (injecting EDTA or another chemical to eliminate something from the body, in this case IRON if there is an iron-overload), bone marrow transplant, genetic counseling

Question 33

What is sickle cell anemia?

Answer 33

Genetically determined defect of hemoglobin synthesis resulting in hemoglobin instability and insolubility
Sickled cells cause vascular occlusion leading to recurrent painful episodes. Also they have severe anemia and RBCs of different shapes and sizes

Question 34

Sickle cell anemia symptoms and treatment?

Answer 34

Symptoms: occlusion of small arteries causes pain, ischemia and loss of function. Increased hemolysis of RBC in the spleen causes severe anemia, hyperbilirubinemia, and jaundice
Treatment of choice is stem cell transplant, these people can die without the transplant

Question 35

What are normocytic normochromic anemias?

Answer 35

Insufficient number of normal RBCs

Aplastic anemia, hemolytic anemia, and anemia of chronic disease

Question 36

Aplastic anemia: What is it, what are the causes?

Answer 36

(Plastic = growth, so aplastic=no growth)
Pancytopenia- decreased/absence of all 3 blood types due to bone marrow failure or suppression in production, normocytic-normochromic anemia
Associated with pure red cell aplasia and fanconi anemia (genetic, induces pancytopenia by defects in DNA repair)
There is a lesion in the bone marrow (increased yellow marrow = fat)
Caused by autoimmune response against hematopoietic stem cells

Question 37

Aplastic anemia: diagnosis and treatment?

Answer 37

Diagnosis: 3 blood levels are reduced, bone marrow biopsy confirms by showing high fat content
Treatment: bone marrow or peripheral blood stem cell transplant, if not possible then immunosuppression therapy is the next option

Question 38

Hemolytic anemia, what is it and what are the types?

Answer 38

Normocytic-normochromic anemia that causes premature/accelerated destruction of RBCs, can be inherited or acquired
Types of autoimmune hemolytic anemia: warm hemolytic anemia (most common, IgG), cold agglutinin hemolytic anemia (IgM), cold hemolysin hemolytic anemia (IgG)

Question 39

What are the hapten model, immune complex model, and autoimmune model?

Answer 39

Hapten model- acquired hemolytic anemia due to drug induced response by allergy to antibiotics, IgG response
Immune complex model- occurs when RBCs have surface receptors that bind to complement system, circulating immune complexes (with quinidine administration), this results in hemolysis
Autoimmune model- administration of a drug induces an immune response against RBCs

Question 40

Hemolytic anemia: symptoms, diagnosis?

Answer 40

Symptoms: jaundice due to heme destruction
Diagnosis: bone marrow studies (increased erythrocyte precursors), blood tests
Treatment: various, remove causative agent

Question 41

Anemia of Chronic Disease (ACD)

Answer 41

Mild to moderate anemia caused by AIDS, RA, lupus erythematous, hepatitis, and malignancies
This leads to decreased erythrocyte life span, ineffective bone marrow response to EPO, and altered iron metabolism
Treatment of the underlying disorder will treat ACD

Question 42

What is polycythemia? What is relative vs. absolute (primary, secondary) polycythemia?

Answer 42

A rare Myeloproliferative RBC disorder causing over-production of RBCs
Relative caused by dehydration
Absolute can be primary, an abnormality of bone marrow stem cells (polycythemia vera), or secondary, an increase in EPO in response to hypoxia or tumors

Question 43

Polycythemia vera: symptoms, treatment?

Answer 43

Symptoms: blood tests show increase in all blood cells, splenomegaly, increased sensitivity to growth factors, increased progenitors in bone marrow, associated with leukemias
Treatment: Minimize risk of thrombosis, prevent progression, phlebotomy

Question 44

Leukocytosis vs. Leukopenia (Quantitative disorders)

Answer 44

Leukocytosis increased WBC, normal response to stressors

Leukopenia: decreased WBC, predisposed to infection

Question 45

Infectious Mononucleosis: what is it, what are the symptoms?

Answer 45

Acute, self-limiting infection of B lymphocytes transmitted by saliva
Commonly caused by Epstein-Barr virus (EBV), B cells have an EBV receptor site
Flu like symptoms

Question 46

Leukemia: what is it and what are the causes?

Answer 46

Malignant disorder of the blood or blood-forming organs causing excessive accumulation of leukemic cells (one progenitor cell undergoes malignant transformation)
Genetic abnormality is caused by translocation between chromosome 9 and 22 (Philadelphia chromosome)

Question 47

Chronic vs. Acute leukemias

Answer 47

Acute has blast cells affected that are undifferentiated/immature
Chronic has abnormalities with the mature cell
*Myeloid vs. Lymphoid is classified based on the cell origin

Question 48

ALL vs. AML vs. CML vs. CLL

Answer 48

ALL greater than 30% lymphoblasts in the blood or bone marrow, most common in children
AML abnormal proliferation of myeloid precursors found in the bone marrow or peripheral blood, most common in adults
CML myeloproliferative disorder such as polycythemia vera and thrombocythemia, has a chronic phase, accelerated phase, and terminal phase
CLL accumulation of B lymphocytes in which B cells fail to mature

Question 49

Malignant Lymphoma: what is it, what are the types?

Answer 49

Cancers that begin malignant transformation of a lymphocyte and proliferation of lymphocytes, histiocytes, their precursors and derivatives in lymphoid tissues causing injury to DNA of the lymphocyte
Types: Hodgkin’s and Non-Hodgkin’s (B,T, NK cell neoplasms)

Question 50

Hodgkin’s vs. Non-Hodgkin’s Lymphoma: what type of cells are there, what are the causes?

Answer 50

Hodgkin’s: Reed-Sternberg cells are necessary for diagnosis, they are altered B cells
Non-Hodgkin’s: no Reed-Sternberg cells, instead changes in B cells, T cells or NK cells, due to abnormalities in proto-oncogenes and tumor-suppressor genes. Can be caused by chromosome translocations, viral/bacterial infections, environment, immunodeficiencies, or autoimmune disorders

Question 51

Hodgkin’s vs. Non-Hodgkin’s: Where is the nodal involvement and is extranodal involvement common or rare? Is the disease rarely or often localized?

Answer 51

Hodgkin: localized to single axial group, mesenteric nodes rarely involved, contiguity and orderly spread, RARE extranodal involvement, extent of disease is OFTEN localized
Non-Hodgkin: Multiple periphery nodes, mesenteric nodes commonly involved, noncontiguous, COMMON extranodal involvement, RARELY localized

Question 52

What is Burkitt lymphoma?

Answer 52

Translocation between MYC (responsible for cell proliferation) to IgG gene which makes a hyperactive gene that enhances cell proliferation AND impairs apoptosis
This effects B lymphocytes and secondary lymphoid organs

Question 53

What are some Burkitt Lymphoma treatment options?

*Don’t worry about the names of the meds, but what do they do and why is it useful?

Answer 53

EPOCH (causes DNA error leading to apoptosis) and Rituximab (targets cell surface protein and enhances clearance)
Prednisone as an immunosuppressant because of the B cell issues
Meds that are immunosuppressants, cause apoptosis, arrest the cell cycle are good meds for this

Question 54

What is Virchow’s triad? What is it used for?

Answer 54

Thrombosis!

Endothelial injury, hypercoagulability, and abnormal blood flow are the three contributing factors

Question 55

What is the criteria for thrombocytopenia?

Answer 55

Platelet count less than 100 k/mm^3
Spontaneous bleeding 10-15 k/mm^3
Usually secondary to conditions that decrease platelets/ platelet survival

Question 56

What are these 2 types of thrombocytopenia: ITP and TTP?
ITP= Immune Thrombocytopenic Purpura
TTP= Thrombotic Thrombocytopenic Purpura

Answer 56

Immune Thrombocytopenic Purpura (ITP): platelets are being DESTROYED by autoimmune disorder.
Thrombotic Thrombocytopenic Purpura (TTP): platelets AGGREGATE and occlude capillaries, it is a deficiency in the protease cleaving of vWF resulting in platelet microthrombi
Both ITP and TTP can be congenital or acquired

Question 57

What is DIC (Disseminated Intravascular Coagulation)?

Answer 57

Widespread of thrombin with rapid consumption of platelets and coagulation proteins, making it “consumptive coagulopathy”, leads to widespread ischemia, infarction, and hypoperfusion which activates the fibrinolytic system (plasmin)
Steps: suppress homeostasis, induce TF (tissue factor) release, fibrin clots, fibrinolysis, diminished fibrinolysis (can’t keep up with the clots that are made), consumption of platelets and clotting factors
Labs show increased FDPs and D-dimer
Reminder: fibrin makes the clot, so when we break it down we get FDP (fibrin degradation products)