PBL B9 W6

Question 1

Acute leukaemia

Answer 1

Excessive proliferation of immature blood cells called blast cells which overcrowd the bone marrow and result in pancytopenia, requiring immediate treatment due to fast onset.

Question 2

Chronic leukaemia

Answer 2

Gradual increase in mature but dysfunctional WBCs.

Question 3

Chronic myeloid leukaemia

Answer 3

Bone marrow cancer of the myeloid cells which are small and mature and occurs later in life, with onset being around 40-60 years old. The myeloid cells are dysfunctional but mature and there are very few blast cells.

Question 4

Blast cells

Answer 4

Large immature precursor cells with little cytoplasm in cancer that proliferate excessively in the bone marrow and take up so much space in the bone marrow which prevent the production of other blood cells, such as erythrocytes and platelets, leading to anaemia and thrombocytopenia. Blast cells can differentiate into myeloid cells or lymphoid cells.

Question 5

Chronic myeloid leukemia-cause

Answer 5

Translocation of BCR on chromosome 9 and ABL on chromosome 22 which results in the transcription of BCR-ABL mRNA -> BCR-ABL fusion protein which is tyrosine kinase that causes auto-phosphorylation for increased cell proliferation and inhibition of apoptosis in haematopoietic myeloid cells.

Question 6

CML- blood smear

Answer 6

High levels of neutrophils at all stages. Myeloid hyperplasia of the bone marrow. Increased basophils and eosinophils occur as disease progresses. No recurrent infections because it is a chronic mature condition so granulocytes are functional. Thrombocytosis (high platelet), normocytic anaemia.

Question 7

What are the stages of CML?

Answer 7

Chronic, acute and blast phase

Question 8

What is chronic phase of CML?

Answer 8

Asymptomatic or mild symptoms and patients are responsive to treatment. Includes fever, night sweats, weight loss and fatigue.

Question 9

What is the accelaratory phase?

Answer 9

Acceleratory phase: splenomegaly occurs and there is basophilia

Question 10

What is blast phase?

Answer 10

CML generally switches to AML with excessive blast cell production or minorly ALL and rapid bone marrow failure

Question 11

CML- symptoms

Answer 11

Weight loss, fatigue, night sweats. Patients with cancer have painless lymphadenopathy with hepatomegaly and splenomegaly due to metastasis in the bloodstream and infiltration by neutrophils.

Infarction due to splenomegaly causes friction heard through a stethoscope. There is a feeling of fullness in the abdomen.

Question 12

Treatment of CML

Answer 12

Generally treated with imatinib to inhibit the action of tyrosine kinase for downstream cell signalling for increased myeloblast production

Question 13

AML

Answer 13

Excessive proliferation of myeloid cells. There is a high number of myeloblasts which overcrowd the bone marrow and lead to pancytopenia and enter the bloodstream to cause hepatosplenomegaly, cranial abnormalities. There are bleeding disorders due to thrombocytopenia, anaemia and low WBC count so immunosuppression is characteristic. This condition usually occurs with the same onset as CML of 40-60 years old.

Question 14

Causes of AML

Answer 14

It is caused by a genetic mutation in cell production in the bone marrow with risk factors including:
 Anti-neoplastic agents (chemotherapy)
 Smoking
 Radiation.
 Genetic conditions such as Down’s (Trisomy 21), Klinefelter (47 XXY) or Turner’s (45 X)

Question 15

AML- symptoms

Answer 15

Blood smear shows thrombocytopenia, high WBC count initially with eventual low WBC count and immunosuppression, and normocytic or macrocytic anaemia.

Question 16

Symptoms of AML

Answer 16

Fatigue, infections and mucosal bleeding due to thrombocytopenia. There is painless lymphadenopathy and hepatomegaly with fatigue.

Question 17

Lymphoblast features

Answer 17

no granules, scarce cytoplasm, less prominent nucleoli. They are either pre-B lymphoblasts, B lymphoblasts or T lymphoblasts.

Question 18

CLL

Answer 18

Features include lymphocytosis with smudge cells (because it is dysfunctional) which progresses -> lymphadenopathy -> hepatosplenomegaly -> anaemia -> thrombocytopenia as the fewer blood cells being produced, the greater the number of immature lymphoblast cells filling the bone marrow which means there is a worse prognosis.

There is low white blood cell count and it typically affects elderly Caucasian males.

Question 19

ALL

Answer 19

Most common leukaemia which typically has pre-B lymphoblasts due to t 9:22 translocation with bad prognosis or 12:21 translocation with good prognosis. Symptoms are generally fatigue, mucosal bleeding and hepatosplenomegaly. Bone marrow is overcrowded with lymphoblasts.

Greater risk in children, especially in those with Down’s syndrome.

Question 20

SPIKES pathway

Answer 20

S: SETTING up the consultation of who, what, where
P: PERCEPTION by patient of their condition
I: INVITATION to find out how much the patient wants to know.
K: KNOWLEDGE provided to the patient on diagnosis, treatment, prognosis, support
E: EMOTIONS of the patient addressed with empathetic response
S: STRATEGY and summary to provide patient follow through

Question 21

Cytogenetics

Answer 21

Microscopic examination of chromosomes during mitosis

Question 22

Types of cytogenetics

Answer 22

Karyotyping of living cells using Giesma staining for G banding to detect changes in chromosomal material such as translocation
Single nucleotide array which detects loss of heterozygosity with nucleotide strands attached to solid surface

Question 23

Allogenic stem cell transplant

Answer 23

stem cells that are genetically dissimilar are taken from healthy donor.

Question 24

Alkylating agents

Answer 24

Form a covalent bond with DNA for the attachment of an alkyl group to DNA to cause crosslink formation which prevents replication and transcription beyond that point and leads to DNA fragmentation and apoptosis. It is a cell-cycle independent drug.

Question 25

Anti-metabolites

Answer 25

Interfering with the conversion of dUMP -> dTMP and methylene folate -> DHF by inhibiting thymidylate synthase. Alternatively, they can act by inhibiting DHF reductase for the conversion of DHF -> THF to form thymine. Anti-metabolites have a similar structure to DNA and RNA nucleotides and can be incorporated into the strand to cause apoptosis. They only work in the S phase so are cell-cycle dependent.

Question 26

Topisomerase inhibitors

Answer 26

Inhibiting the action of topoisomerase for the relaxation of the adjacent DNA supercoil by introducing single or double stranded DNA breaks and the process of DNA ligation for replication to occur. These inhibitors cause apoptosis to occur. Eg etoposide

Question 27

Microtubules function

Answer 27

Responsible for determining cell shape and locomotion in mature cells. They are composed of alpha-tubulin and beta-tubulin. During mitosis, microtubules extend out from the centrosome to assemble the mitotic spindle for chromosome distribution in daughter cells for DNA replication.

Question 28

Side effects of chemotherapy- cause

Answer 28

The cytotoxic drug being non-discriminate and targeting highly proliferating cells including.

Question 29

Gamma rays

Answer 29

Originate in cell nucleus of radioactive isotopes

Question 30

Types of brachytherapy

Answer 30

Sealed source
Unsealed source: capsulated drugs with high affinity for specific cells

Question 31

How does resistance to EGFR receptor occur?

Answer 31

Due to T790M mutation in cancer cells

Question 32

How does the immune response work against cancer cells?

Answer 32

Antigens shed by cancer cells are taken up by dendritic cells to prime T cells. T cells bind to cancer cells to induce apoptosis however cancer cells with PDGR-1 receptor induce T cell suppression