W1P3

Question 1

What are platelets

Answer 1

Cell fragments that function as part of hemostasis

• Initiate thrombus formation with overt vascular injury
• Proposed role in wound repair, innate immune response, metastatic malignancy

Question 2

What is the lifespan of platelets

What is the normal count?

Answer 2

Life span of 7-10 days
Normal count 150 x 109/L – 450 x 109/L
1/3 of platelets are always transiently sequestered in the spleen

Question 3

Platelet production

- how is production regulated?

Answer 3

Bone marrow production of megakaryocytes stimulated by thrombopoietin

Megakaryocytes shed platelets from their cytoplasm – each produces 1000-3000 platelets

Thrombopoietin induces megakaryocyte maturation and differentiation
Produced in liver
- c-mpl receptors expressed on circulating platelet mass provide feedback loop
- Decreased platelet mass = decreased amount of c-mpl receptors = decreased clearance of TPO = resulting increase in megakaryocyte production

Question 4

What is Primary Hemostasis

- What are the four steps?

Answer 4

Hemostasis is process by which bleeding is stopped at site of injury with normal blood flow elsewhere

Four steps

1. Adhesion to injured site
2. Activation and secretion
3. Aggregation
4. Interaction with coagulation factors

Question 5

What are some strong vs weak physiologic stimuli of platelets?

Answer 5

strong: collagen, thrombin

Weak: ADP, epinephrine

Question 6

How does endothelium usually maintain anticoagulant surface?

- What happens in injury?

Answer 6

via. production of NO and prostacyclin

INJURY: exposes the subendothelial matrix -> exposed collagen activated platelets

Question 7

What are the two major platelet-collagen receptors?

Answer 7

GPIa/IIa (alpha 2, betal 1) - platelet adhesion
GPVI - platelet activation

inheritied loss of GPIa = mild bleeding diathesis BUT
congenital absence of GPVI = spontaneous bleeding episodes

Question 8

What receptor does Thrombin use to activate platelets?

Answer 8

platelets express PAR: G proteins coupled Protease-Activated Receptors

PAR1 - high affinity, PAR4- low affinity receptor

Question 9

P2Y12 receptor involvement in platelets?

- What is it inhibited by?

Answer 9

ADP binds to two G-protein coupled purinergic receptors – P2Y1 and P2Y12
When activated, P2Y12 induces platelet secretion and stable aggregation
Activated platelets secrete ADP which works in a paracrine/autocrine manner to recruit and stimulate more platelets enhancing aggregation
Activity of the P2Y12 receptor is inhibited by clopidogrel

Question 10

Platelet Adhesion

Answer 10

Platelet surface receptor GPIb/IX/V complex binds exposed von Willebrand factor (vWF) in the subendothelial matrix

Von Willebrand factor (vWf) is a large multimeric protein secreted by endothelial cells and megakaryocytes

A. vWf adheres to subendothelial collagen conformational change allowing it to bind to GPIb-V-IX
B. Rolling process slows platelet transit and allows platelet signalling receptor, GPVI to bind collagen
C. Signalling cascade leads to activation of integrin α2β1 (GPIa/IIa)  platelet firmly adheres to vessel wall

Question 11

Platelet Aggregation

Answer 11

GPIIb/IIIa complex (integrin alpha IIb beta 3) is most commonly expressed receptor on platelet surface

Stimulation of platelet induces conformational change in GPIIb/IIIa rendering it a high-affinity receptor for fibrinogen

GPIIb/IIIa binds vWF affixed to the subendothelial matrix cytosolic component of GPIIb/IIIa adheres to the platelet cytoskeleton and induces platelet spread and clot retraction

Question 12

What are the two platelet granules

Answer 12

Dense granules:
Contain platelet agonists
-ADP, ATP, serotonin

Alpha granules:
Contents serve to enhance platelet adhesion
-Fibrinogen, vWF, fibronectin

Question 13

Define sequestration

Answer 13

To hide or isolate

Question 14

Relationship between platelet count and risk of bleeding?

Answer 14

Minimal at 50 x 10^9/L
spontaneous bleeding at <20 x 10^9/L
severe, fatal: <5 x 10^9/L

Question 15

Thrombocytopenia causes

Answer 15

Decreased platelet production
Increased destruction or consumption (immune-mediated and non-immune-mediated)
Increased splenic sequestration of platelets with normal platelet survival
Pseudothrombocytopenia

Question 16

Pseudothrombocytopenia

Answer 16

In vitro agglutination of platelets
15-30% of all isolated thrombocytopenia

Associated with use of EDTA as anticoagulant in tube
- Confirm by ordering smear of CBC showing thrombocytopenia with automated counting

*Can be avoided by using citrate/heparin as anticoagulant

Question 17

What are the DDx for isolated thrombocytopenia?

Answer 17

Primary immune thrombocytopenia (ITP)
Inherited thrombocytopenia
Marrow failure/myelodysplastic syndrome/malignancy
Splenic sequestration

Question 18

ITP

Answer 18

Primary immune thrombocytopenia

-otherwise healthy looking kid (NORMAL CBC/smear) , minimal history/recurrence, apart from petechie

Immune-mediated destruction of otherwise normal platelets

• Triggered by viral infection, other immune phenomenon
• most commonly age 2-5 y/o
• Natural history is self-resolution within 6 months (75-80%)
• Most presentations include mild bruising, petechiae

IgG directed against platelet membrane antigens, most commonly GPIIb/IIIa ie integrin αIIbβ3

• Increased clearance by splenic macrophages
• Production inhibited

Question 19

Management of ITP

Answer 19

Management options include observation or active therapy with corticosteroids, IVIg, or anti-D (if Rh-positive)

Treatment options include
IVIg (80% effective, increase within 24h, peak within 2-7d)
Short-course corticosteroids (70-80% effective, increase within 48h)
Other:
IV anti-D (“blackbox” warning)
Tranexamic acid may be used as adjunct (not if hematuria)
Platelet transfusion contraindicated except for acute life-threatening bleed or if urgent surgery required

Question 20

Menorrhagia

- CBC finding

Answer 20

is a condition marked by abnormally heavy, prolonged, and irregular uterine bleeding. Women with this condition usually bleed more than 80 ml, or 3 ounces, during a menstrual cycle. The bleeding is also unexpected and frequent.

otherwise healthy looking, no pain, normal physical exam

CBC finding: HIGH Mean Platelet Volume (MPV)

Question 21

What is used to measure platelet activation and aggregation in vitro?

Answer 21

Platelet agonists
(ensure pts not on meds that interfere with platelets) 

Common agonists are: 
ADP
collagen 
Epi
Ristocetin

Question 22

Bernard- Soulier Syndrome

• characteristic symptoms?
• lab findings include?

Answer 22

Autosomal recessive platelet disorder
Deficiency of GPIb receptor for vWF, which leads to impaired platelet adhesion
RARE, affects males and females equally

Symptoms include spontaneous/excessive mucocutaneous bleeding; varying bleeding severity throughout life. Can be diagnosed in adulthood (can be mistaken for chronic ITP)

Question 23

Lab findings and Management for Bernard-Soulier Syndrome?

Answer 23

Laboratory findings include
Macrothrombocytopenia, normal coagulation studies (PT, aPTT)
No aggregation with ristocetin, that is uncorrected by addition of plasma (vWD would correct)

Management includes
Avoidance of anti-platelet therapies
Transfusion for bleeding, or pre-procedural

Question 24

What are Bone Marrow Cancers

• general lab findings
• progression of disease?

Answer 24

Myeloid malignancies – cancers derived from the hematopoietic stem or progenitor cell

• Affect predominately the bone marrow
• Effects are seen primarily in the blood

Lab Findings:
a. Cytopenias – decrease in one or more cell lines
Anemia, thrombocytopenia, leukopenia, neutropenia – etc
b. Pancytopenia – decrease in all cell lines
c. May also see elevation in one or more line
Erythrocytosis, thrombocytosis,leukocytosis, neutrophilia – etc

May be very aggressive or more indolent cancers

Question 25

Define Leukemia

Answer 25

By definition a leukemia is a myeloid or lymphoid cancer that involves the bone marrow as its primary site. May be acute or chronic

Question 26

Acute Leukemia

Answer 26

Rapid proliferation of abnormal clone that overtakes bone marrow and prevents normal hematopoiesis Severe anemia, thrombocytopenia, and neutropenia Patients are symptomatic at the outset - Rapidly progressive - Death within weeks to months Cells show impaired differentiation - Immature appearance - Little functionality

Question 27

Chronic Leukemias

Answer 27

Differentiation is more or less intact. Leukemic cells resemble mature, normal white cells and may even function normally Clone grows such that for most of the disease course, the growth of normal blood cells is not significantly impaired. - Generally follow a more indolent course Patients often present because of an abnormal CBC (usually elevated white count) often asymptomatic for long periods; life expectancy measured in years.

Question 28

Can you have leukemia if you have a perserved blood cell function and numbers?

Answer 28

Yes, this is what CHRONIC leukemia looks like

Question 29

Myeloproliferative Neoplasms

Answer 29

Cancerous stem cell disorder of the marrow Excessive production of one or more cell lines- disordered proliferation of cells Relatively intact differentiation May affect WBC, RBC or platelets May also see proliferation of other cells such as fibroblasts – myelofibrosis – and other, rarer entities with accumulation of one or more mature cell lines in the marrow and blood

Question 30

Myelodysplastic Syndromes

Answer 30

Cancerous stem cell disorder with Impaired differentiation Results in cytopenias: Increased growth of cells inside the marrow Decreased cell numbers outside the marrow Faulty cells die (apoptosis) before they get into circulation May evolve to acute myeloid leukemia over time.

Question 31

What is the Origin of Myeloid Cancers

Answer 31

All of these cancers occur as the result of genetic changes in the hematopoietic stem cell Effects maturation and growth of all progenitor cells Several changes likely necessary to achieve transformation Changes may be at chromosomal or molecular level.

Question 32

What cytogenetic changes are associated with development of Leukemia and related disorders

Answer 32

Changes at the level of the chromosome involving large amounts of DNA at a time May result in deletion of whole genes, even whole chromosomes Duplication of DNA may also occur Translocations of DNA from one chromosome to another May result in fusion genes Molecular genetic changes: a. Smaller changes at critical points in DNA Insertions/deletions Point mutations Missense and nonsense mutations b. Epigenetic changes Modifications to DNA and chromosomes that alter transcription without changing the base sequence Methylation of cytosine histone acetylation

Question 33

What are the 4 broad categories of Leukemias?

Answer 33

Acute lymphoblastic leukemia (ALL) Acute myeloid leukemia (AML) Chronic lymphocytic leukemia (CLL) Chronic myeloid leukemia (CML)

Question 34

The Blast Cell | - what amount signifies Acute leukemia?

Answer 34

Immature hematopoietic cell with minimal differentiation Characterized by: Somewhat larger size than most hematologic cells Large nucleus Very “lacy” or “open” nuclear material - DNA is not condensed as in mature blood cells May have a prominent nucleolus or nucleoli By definition having a blast count > 20% in the bone marrow is an acute leukemia (myeloid or lymphoid)

Question 35

CLL - Subtype? - Marker? - Clinical course?

Answer 35

Chronic Lymphoid Leukemia - A subtype of B cell lymphoma Cells are mature B lymphocytes that may circulate in blood or grow in lymphoid organs (spleen, nodes) - Atypical CD5 expression (CD5 is a T cell marker) Cells appear indistinguishable from small lymphocytic lymphoma (SLL) cells Clinical course is like an indolent lymphoma Natural history measured in years to decades in most (but not all) cases Responds to many of the same agents as B cell lymphomas

Question 36

What is the Pathobiology of Acute Leukemia

Answer 36

Occurs in a single stem or progenitor cell - Evidence for this includes: - shared chromosomal abnormalities - rearrangement of Ig or TcR genes in ALL Mutations appear to be common in mechanisms affecting transcription and gene modification - e.g. 25% of all AML is initiated by a mutation in the gene DNA methytransferase-3

Question 37

What are some clinical manifestations of Acute Leukemia?

Answer 37

Pancytopenia from marrow failure - May or MAY NOT have leucocytosis with circulating blast cells ``` Constitutional Symptoms: Fevers Fatigue Bone pain* Malaise ``` Direct Tissue Infiltration by blast cells Leukostasis syndromes Tumour Lysis Syndrome Coagulation Disturbances Usually short duration of symptoms (weeks to months)

Question 38

What is Pancytopenia | - Combo of what three CBC findings?

Answer 38

A condition in which there is a lower-than-normal number of red and white blood cells and platelets in the blood 1. Neutropenia/Impaired immunity: - infections, sepsis - Usually bacterial - Fungal infections if pronlonged neutropenia 2. Anemia: - fatigue, pallor - Cardiac ischemia in extreme cases 3. Thrombocytopenia - bleeding, bruising - disseminated intravascular coagulation

Question 39

Leukostasis

Answer 39

Accumulation of blasts in microcirculation with impaired perfusion - lungs: hypoxemia, pulmonary infiltrates - CNS: altered mental status, stroke Risk Features - WBC >> 50 x 109/L (not frequent) - AML > ALL - Monocytic/monoblastic features

Question 40

Infiltration by blast cells - Is common sign of ____ - What does this involve?

Answer 40

Acute Leukemias Involves: - Enlargement of liver, spleen, lymph nodes - Gum hypertrophy - Bone pain Other organs: CNS, skin, testis, any organ...

Question 41

Laboratory features of Acute Leukemia

Answer 41

Pancytopenia - WBC my be low or elevated (blasts) Coagulation abnormalities Electrolytes and renal disturbances - auto tumour lysis syndrome (hyperuricemia, high K, PO4, creat) Increased liver function tests

Question 42

Bone Marrow Studies in Acute Leukemia

Answer 42

Usually necessary for diagnosis Cell morphology must show > 20% immature cells (blasts) to make the diagnosis Confirmation of blast characteristics - Large nuclei with open chromatin and promenent nucleoli are classic features of blasts Myeloid/Lymphoid by morphology Cytochemistry or Flow cytometry Cytogenetics can be done on malignant cells Molecular testing for specific gene defects becoming more routine and bring important information to treatment decisions

Question 43

Acute Promyelocytic Leukemia (APL)

Answer 43

A subtype of AML Different treatment and prognosis: Presents as AML - Pancytopenia - Coagulation disturbances - Frequent - Severe - Lethal - Characteristic morphology t(15;17) in most cases Rare variants About 5-10% of AML Different treatment ***Curable

Question 44

Clinical features of Acute Lymphoblastic Leukemia (ALL)

Answer 44

B lineage vs T lineage 80% are pre B ALL, 20% are T ALL Pre B-ALL is primarily a disease of children 75% of cases occur in children under the age of 6 Most common malignancy among children Peak incidence in children is approximately 2 to 3 years of age Increased risk among children with Downs syndrome About 20% of acute leukemias in adults

Question 45

AML rate in adults vs kids?

Answer 45

AML represents 80% of acute leukemia in adults, but only 20% of acute leukemia in children

Question 46

Morphological Features of Acute Myeloid Leukemia (AML)

Answer 46

Morphology - Usually larger than lymphoblasts, up to the size of a monocyte - Moderate to abundant cytoplasm with or without granules - May contain Auer rods - Sometimes convoluted nucleus with diffuse chromatin and one or more nucleoli Cells usually stain positive for Sudan black or myeloperoxidase

Question 47

Classification of AML is based on?

Answer 47

Degree of differentiation of the blast (defined morphologically and by surface markers) AML M0, M1 and M2 – poorly differentiated and may or may not contain granules M0 and M1 may be difficult to distinguish from ALL AML M4 is similar with a mixture of monocytic and granulocytic features AML M5 cells resemble monocytes

Question 48

Developing targeted therapy in AML

Answer 48

Specific mutations in certain genes appear to be critical in driving the disease Inhibiting function of mutated genes may alter biology and improve outcomes - Easy to inhibit overexpressed or overactive processes - Less clear what to do in cases of gene loss or loss of function Small molecules, antibodies Targets currently in development include - ***FLT-3 – a protein tyrosine kinase overactive in about 30% of AML: inhibitor shown to improve AML outcomes more common in patients over 60, however must consider whether treatment is worth it past that age

Question 49

What is the molecular lesion in APL?

Answer 49

Translocation between - Retinoic acid receptor gene (chromosome 17) - PML gene (chromosome 15) Resultant PML-RARa gene drives disease (normally would have stimulated promyelocytic maturation) Translocation can be detected rapidly with FISH or RT-PCR

Question 50

Treatment of APL

Answer 50

Early recognition of APL Early correction of coagulation abnormalities Early institution of All-trans Retinoic Acid (ATRA) - Specific treatment of APL - Ligand for the PML-RAR protein Addition of arsenic trioxide +/- chemotherapy now considered largely curative in nearly all cases of disease

Question 51

Morphology of ALL?

Answer 51

Blasts are usually small with a high nuclear to cytoplasmic ratio The bone marrow aspirate is usually hypercellular and infiltrated with blasts. To make the diagnosis of ALL, 20% or more of nucleated cells in the bone marrow must be blasts.

Question 52

Cytogenetics in ALL

Answer 52

Prognostically important in B-ALL, less so in T-ALL can help determine if the prognosis is favourable or poor.

Question 53

Prognosis of ALL

Answer 53

Children – Excellent – between 60-90% cure with chemotherapy Infants < 1 year are the exception with poor outcomes Adults – Fair – Only about 40% cure Pediatric regimens appear to be more effective although more toxic to adults Adults treated on pediatric regimens may do better

Question 54

Principles of Acute Leukemia Treatment

Answer 54

Initial chemotherapy is directed at remission induction Decreasing blast count in marrow to < 5% Restoration of normal hematopoesis Usually ~ 4 week period of treatment - Heavy transfusion needs - High risk of infection Usually several more cycles of treatment needed to achieve long-term disease control - Many, but not all patients will ultimately relapse

Question 55

What is Car-T - What is it used to treat? - What cells does it involve?

Answer 55

Immunotherapy – Adoptive Chimeric AntiGEN RECEptor T cells (Car-T) Best established for diseases of B cells expressing CD19 (ALL, CLL, NHL) 1. T cell collection from pt 2. T cell transfection: CAR cell membrane insertion 3. T Cell Adoptive Transfer 4. Patient monitoring

Question 56

Immunotherapy for ACUTE leukemias

Answer 56

``` blinatumumab Bi-specific, T cell Engager Antibody *Anti CD19/CD3 Brings T cells into proximity to target cells (tumour cells) Enhanced immunologic response ```

Question 57

Clinical progression of Myeloproliferative Disorders

Answer 57

Usually patients are asymptomatic for long periods of time After several years may develop to more aggressive disease that mimics acute leukemia In some cases (essential thrombocytosis, polycythemia vera) there is also a tendency for thrombosis to occur

Question 58

What are the four major subtypes of Myeloproliferative Neoplasms

Answer 58

1. Chronic Myeloid Leukemia – mainly white blood cells affected 2. Essential Thrombocytosis – mainly platelets affected 3. Polycythemia vera – mainly rbc cells affected 4. Myelofibrosis – mainly accumulation of bone marrow fibroblasts

Question 59

Chronic Myeloid Leukemia - fall under which type? - Which chromosome is involved - accumulation of which cell type? - differentiation?

Answer 59

- The prototype of the myeloproliferative disorders Transforming event occurs in the hematopoetic stem cell t(9;22) – Philadelphia chromosome bcr-abl fusion gene Results in accumulation of uncontrolled granulocytes Platelets and rbc affected to a lesser extent Differentiation is largely intact in the early stages

Question 60

What are the three phases of CML?

Answer 60

Chronic Myeloid Leukemia ``` 1. Chronic Phase Generally asymptomatic Sometimes vague symptoms (fatigue, night sweats, weight loss) may have enlarged spleen Lasts for 4-7 years ``` 2. Accelerated Phase Increasing numbers of immature (blast cells) Rising or falling platelets, enlarging spleen Evidence of new genetic changes in marrow studies 3. Blast Phse Acute illness occurring when blasts > 20% Rapid collapse of bone marrow with pancytopenia Very similar to AML, but often with higher resistance to chemotherapy Death usually within 6 months if untreated

Question 61

What is the treatment for CML?

Answer 61

Imatinib: abl-kinase inhibitors are mainstay of therapy* Block the action of the fusion protein allowing restoration of normal hematopoiesis Prevent progression to more severe disease and restore normal hematopoiesis Not curative and must be taken indefinitely

Question 62

What are the Myelodysplastic Syndrome (MDS)

Answer 62

The MDSs are characterized by the development of cytopenias, most commonly anemia. Patients may require considerable support with transfusion and other agents to maintain blood counts. In addition to the expected problems from low blood counts: Low white blood cells – frequent infections Low platelets – frequent and serious bleeding Low red blood cells – marked anemia and even ischemia Transfusion-dependent anemia May also have low platelets and/or white blood cells Genetic disease with an enhanced risk of transformation to acute myeloid leukemia. Highly variable prognosis life expectancy a few months to several years

Question 63

What are the causes of MDS

Answer 63

Primary or de novo Usually occurs above age 60 No clear provoking cause Some association with toxins such as benzene, rubber and solvents Therapy-related MDS Secondary to chemotherapy, radiotherapy Usually occurs 3 – 7 years after exposure Worse prognosis with faster transformation to AML MDS may occur secondary to other hematologic disorders Aplastic anemia Myelproliferative neoplasms Paroxysmal nocturnal hemoglobinuria

Question 64

TReatment options for pts with MDS

Answer 64

Myelodysplastic Syndrome low risk: RBC and platelet transfusions high risk: immunosuppresions, chemotherapy, stem cell transplants

Question 65

Which type of disease is driven by bcr-abl kinase?

Answer 65

Myeloproliferative Disease: Increased cell number but intact differentiation May affect one ore more cell lines CML – protoype disease driven by bcr-abl kinase

Question 66

Which type of disease has risk of transforming to AML

Answer 66

Myelodysplastic disease: Low and high risk disease – may transform to AML Impaired Differentiation Increased bone marrow cells with decreased circulating cells

Question 67

Which type of leukemia is most common in adults?

Answer 67

Acute Myeloid Leukemia - Most common in adults - Variable prognosis depending on cytogenetics

Question 68

Which Leukemia has good prognosis with All-trans-Retinoic Acid treatment?

Answer 68

Acute Promyelocytic Leukemia (M3) - PML-RARa gene from translocation of chromosomes 15 and 17 - Good prognosis with All-trans-Retinoic Acid

Question 69

Which Leukemia is most common in children?

Answer 69

Acute Lymphoblastic Leukemia - Most common in children - Excellent response to multiagent chemotherapy if in childhood, prognosis worse in adults

Question 70

What are some cancers of the blood

Answer 70

- Leukemia • Lymphoma • Multiple myeloma

Question 71

Which cancer is most common for ages 0-14?

Answer 71

Leukemia!

Question 72

Define Cancer | Define the "ideal" Cancer treatment

Answer 72

Cancer: altered regulation of cell proliferation and differentiation “Ideal” cancer treatment: eradicate cancer cells without harming normal cells

Question 73

What are the 4 types of Chemotherapeutic drugs?

Answer 73

DNA Alkaylation: Covalently binding DNA Anti-metabolites: blocking DNA replication Microtubules: Messing up the process of cell division Topoisomerase Inhibitors: blocking DNA replication phase These^ are all NON specific, so they will target ALL rapidly proliferating cells. Yet they are still useful, and still used.

Question 74

What are examples of DNA alkylation drugs?

Answer 74

Cyclophosphamide Dacarbazine * non specific drugs

Question 75

What are examples of Anti-metabolite drugs?

Answer 75

Methotrexate R-Fluorouracil Cytarabine

Question 76

Examples of Microtubule drugs

Answer 76

Vincritine Vinblastine Taxols

Question 77

Example of Topoisomerase inhibitor drugs

Answer 77

Daunorubicin DNA damage: Bleomycin

Question 78

Dacarbazine - type - mechanism

Answer 78

DNA alkylating agent - Methylates guanine at the o-6 and N-7 positions

Question 79

What cells does the toxicity of alkylating agents affect? What does Resistance to alkylating agents look like?

Answer 79

To rapidly proliferating cells - Hematopoietic system - GI tract - Gonads ``` Resistance to alkylating agents - Increased inactivation Nucleophilic "trapping agents' - Increased DNA repair - Decreased activation ```

Question 80

Methotrexate

Answer 80

Anti metabolite drug, non specific cancer treatment - it is a folic acid analogue; competively binds to dihydrofolate reductase and inhibits cell division pathway (methyl transfers)

Question 81

5 - Fluorouracil

Answer 81

DNA base modification | type of anti-metabolite drug, non specific cancer treatment

Question 82

Cytarabine

Answer 82

Type of anti-metabolite, non specific cancer drug Modification to the sugar: it competitively inhibits DNA polymerases. it's incorporation into the DNA produces strand break and triggers apoptosis

Question 83

Vinca Alkaloids

Answer 83

from a plant, transformed to Vincristine/Vinblastine - Bind to tubulin, terminate assembly, cause depolymerization of microtubules and mitotic arrest a Microtubule* type of non specific cancer drug

Question 84

Taxols

Answer 84

promote microtubule assembly and inhibit disassembly a microtubule type of non specific cancer drug

Question 85

Daunorubicin (Doxorubicin) - Used to treat? - TYPE - Mechanism

Answer 85

AML ALL CML Topoisomerase inhibitors, non specific cancer drug mechanism: Intercalates in DNA and inhibits topoisomerase II: causes DNA strand breaks

Question 86

Bleomycin

Answer 86

topoisomerase inhibitor type non specific cancer drug Binds to DNA and iron, forms free radicals (ROS), leading to DNA single and double strand breaks and chromosomal aberrations.

Question 87

Prednisone

Answer 87

A type of SPECIFIC target cancer drug Steroid hormone receptor is the target this is a type of glucocorticoid can alter gene expression

Question 88

Imatinib | - What is it used to treat

Answer 88

this is a SPECIFIC cancer drug Cancer specific Tyrosine Kinase Inhibitor (Fused BCR-Abl) fromed by translocation Used to treat CML, chronic myeloid leukemia and ALL, acute lymphocytic Leukemia

Question 89

Rituximab - mechanism - used to treat?

Answer 89

Specific cancer drug: modifies the immune response, it is Anti CD20 mechanism: destroys both NORMAL and MALIGNANT B cells Treats: B cell non Hodgkins Lymphoma that is CD20+ Chronic Lymphocytic Leukemia CLL

Question 90

What are drugs that block T cell priming?

Answer 90

Ipilimumab: block CTLA-4 Premrolizumab, Nivolumab: block PD-1/PD-L1 treats: Hodgkin Lymphoma plus other cancers

Question 91

Brentuximba Vedotin What is it? What does it target? What does it treat?

Answer 91

what is it: : an antibody-drug conjugate Targets tumor cells expressing CD30 (HL). Conjugated via a protease-cleavable linker to a potent anti-microtubule agent treats: specific lymphomas

Question 92

Venetoclax - Target - Treats?

Answer 92

Targets BCL2, increasing apoptosis | Treats: B cell malignancies

Question 93

CAR T cell therapy | - steps

Answer 93

1. remove blood to get T cells 2. Make CAR T cells in the lab, proliferate 3. Infuse CAR T cells into patients 4. CAR T cells bind to cancer cells and kill them

Question 94

Principles of Classical Cancer chemotherapy

Answer 94

1. High dose- maximize cell kill with tolerable toxicity 2. Intermittent 3. Drug Combinations

Question 95

Drug combinations - delay resistance | What are the four principles

Answer 95

1. Efficacy 2. Toxicity 3. Optimum scheduling 4. Mechanism of interaction

Question 96

What is the drug approach to Acute Lymphoblastic Leukemia?

Answer 96

Vincristine Prednisone Doxorubicin/Daunorubicin

Question 97

What is the drug approach to Chronic Myelogenous Leukemia

Answer 97

Philadelphia chromosome^ drug: Imatinib*

Question 98

Sample approach to Hodgkin Lymphoma

Answer 98

Think ABVD Doxorubicin (Adriamycin) Bleomycin Vinblastine Dacarbazine Brentuximal vedotin Nivolumab or Pembrolizumab

Question 99

Sample drug approaches to Non-Hodgkin Lymphoma

Answer 99

``` Think CDVP Cyclophosphamide Doxorubicin Vincristine Prednisone ``` *Rituximab