Haematology

Question 0

Process of receptor mediated apoptosis

Answer 0

Ligand binds FAS connected to death receptor
Triggers intracellular cascade 
Activation of caspases
DNA digestion
Disintegration of cytoskeleton 
Apoptosis

Question 1

Two mechanisms of apoptosis

Answer 1

Receptor mediated

Intrinsic mitochondrial

Question 2

Mechanism of intrinsic mitochondrial apoptosis

Answer 2

Irreversible damage to cell constituents
BCL family controls mitochondrial membrane permeability 
Release of cytochrome C
React with members of apoptosis cascade
Activation of caspases
Apoptosis

Question 3

How do gain of function mutations occur

Answer 3

Amplification of gene
Mutation of gene (product no longer sensitive to control mechanisms)
Mutation of regulator genes (oncogene now unopposed)
Translocation (production of fusion genes, transfer of gene to region that is actively transcribed)

Question 4

How does loss of function mutation occur

Answer 4

Large deletions
Small deletions eg frame shift
Mutations causing 1. Stop codon 2. Disruption of promoter 3. Splice region - less active protein.

Question 5

Why stem cells often origin of haemopoietic malignancy

Answer 5

Long lived - accumulate mutations
Capacity for self renewal - feed malignancy
Actively transcribe regulatory proteins

Question 6

Phenotype of malignancy depends on…

Answer 6

Predominant cell lineage
Proliferation rate
Degree of differentiation
Amount of apoptosis

Question 7

Why differentiate between ALL and AML

Answer 7

Very different treatment and prognosis. Therefore misdiagnosis = poorer prognosis

Question 8

How to diagnose acute leukaemia

Answer 8

1. FBC (differential and morphological review)
2. Bone marrow aspirate and trephine biopsy
3. Additional tests ( LP, DIC screen, HIV, electrolytes and renal Fx)

Question 9

How do you manage a patient with leukaemia

Answer 9

Anaemia = exclude bleeding, give irradiated RBC
Thrombocytopenia = transfuse platelets
Prevent infection
Prevent tumour lysis/ gout
Prevent nausea 
Treat infections

Question 10

What is induction therapy

Answer 10

Chemo to induce remission

Question 11

What is consolidation therapy

Answer 11

Further chemo after remission that’s the same or more intense than induction which aims to eradicate disease

Question 12

What is maintenance therapy

Answer 12

Less intense (often oral) helps to maintain remission.

Question 13

Anti metabolites …

Answer 13

Metabolite of drug incorporated into DNA and inhibits DNA polymerase

Question 14

Anrthracyclins

Answer 14

Bind DNA and prevent/ interfere with mitosis

Question 15

Topiosomerase inhibitors

Answer 15

Induce DNA strands to break, inhibiting mitosis

Question 16

Vinca alkaloids

Answer 16

Damage Mitotic spindle

Question 17

Corticosteroids …

Answer 17

Lysis of RBC

Question 18

Folate antagonists….

Answer 18

Deplete intracellular folate and block purine/pyrimidine synthesis by inhibiting dihydrofolate reductase

Question 19

Purine analogues…

Answer 19

Inhibit purine synthesis

Incorporated into DNA

Question 20

Uses of BM transplant

Answer 20

Eradicate aggressive cancers

Rescue patients treated with high dose chemo

Question 21

Types of BM transplant

Answer 21

AUTOLOGOUS - persons own blood

ALLOGENIC - matched donor, more risk

Question 22

Complications of chemo

Answer 22

Normal BM ‘‘killed’’
GIT cells affected - nausea, mucho sites
Immunosuppression - severe infection
Tumour lysis syndrome

Question 23

Prognosis in AML dependent on..

Answer 23

Cytogenetics of cells
Age
Primary vs secondary AML
WCC and diagnosis
Response to induction therapy
Performance status of patient

Question 24

Poor risk factors in ALL

Answer 24

Age >35
High WCC at diagnosis
CNS disease at presentation 
t(9:22) or t(4:11)
More then four weeks to achieve remission

Question 25

Wat info does family/patient need

Answer 25

Info RE diagnosis and therapy
First admission one month
Need to be close to transplant centre - 1 year
Adult/ kid miss a year or more of school

Question 26

P53 raises the level of what to cause apoptosis

Answer 26

BAX

Question 27

Three features of bone marrow failure and clinical consequences

Answer 27

Anaemia - fatigue, pallor
Neutropenia - susceptibility to infections
Thrombocytopenia - bleeding

Question 28

Type of chromosomal abnormalities that may be found in acute leukaemia

Answer 28

Hyperdiploidy
Hypodiploidy
Deletions
Translocations

Question 29

Define proto oncogenes

Answer 29

Normal genes

Code for proteins involved in regulation of cell growth, proliferation and differentiation.