Leuk

Question 1

Define leukaemia

Answer 1

→malignant disorders of haematopoietic stem cells characteristically associated with increase number of white cells in bone marrow or/and peripheral blood.

Question 2

What are the two features of haematopoietic stem cells?

Answer 2

→Multipotent- can give rise to cells of every blood lineage

→Self maintaining- a stem cell can divide to produce more stem cells

Question 3

What are the three features of progenitor cells?

Answer 3

→Can divide to produce many mature cells

→But cannot divide indefinitely

→Eventually differentiate and mature

Question 4

What is the difference in morphology of undifferentiated and differentiated progenitor cells?

Answer 4

→cannot tell the difference between them morphologically because they do not show the characteristics of mature cells.

Question 5

What is meant by leukaemia being clonal?

Answer 5

→all the malignant cells derive from a single mutant stem cell.

Question 6

What are the first symptoms of all leukaemia?

Answer 6

→Abnormal bruising-commonest
→Repeating abnormal infection
→Sometimes anaemia
→Fever

Question 7

What are the three ways of diagnosing leukaemia?

Answer 7

→Peripheral blood blasts test (PB)
→ Bone marrow test/biopsy (BM)
→Lumbar puncture

Question 8

Why is peripheral blood test used in leukaemia diagnosis?

Answer 8

→looks for blasts and cytopenia.

→ if >30% blasts are suspected of acute leukaemia.

Question 9

Where is bone marrow taken from?

Answer 9

→taken from pelvic bone and results compared with PB.

Question 10

Why is lumbar puncture used in leukaemia diagnosis?

Answer 10

→to determine if the leukaemia has spread to the cerebral spinal fluid (CSF)

Question 11

What techniques are involved in molecular and pathophysiological characterisation of leukaemia testing?

Answer 11

→Cytomorphology
→Immunophenotyping
→Next Generation Sequencing (NGS)
→Flow cytometry
→Fluorescence in situ Hybridation (FISH)

Question 12

What type of leukaemia are sometimes hereditary?

Answer 12

→Chronic Lymphocytic Leukaemia (CLL)

Question 13

What are some chromosome aberrations which may be genetic risk factors for leukaemia?

Answer 13

→Translocations (e.g. BCR-ABL in CML).

→Numerical disorders (e.g. trisomy 21-Down syndrome).

Question 14

What are some inherited immune system problems that predisposes to leukaemia?

Answer 14

→Ataxia-telangiectasia,

→Wiskott-Aldrich syndrome

Question 15

What are some genetic mutations that predisposes to leukaemia?

Answer 15

→TP53- Li-Fraumeni syndrome,

→NF1-Neurofibromatosis

Question 16

What are some environmental risk factors that predisposes to leukaemia?

Answer 16

→Radiation exposure
→Exposure to chemicals and chemotherapy
→Immune system suppression

Question 17

What are some risk factors linked to childhood leukaemia?

Answer 17

→Exposure to electromagnetic fields
→Foetal exposure to hormones
→Parent’s smoking history
→Infections early in life
→Mother’s age when child is born

Question 18

What are the classifications of leukaemia?

Answer 18

→Acute Lymphoid Leukaemia (ALL)
→Acute Myeloid Leukaemia (AML)
→Chronic Lymphoid Leukaemia 
(CLL)
→Chronic Myeloid Leukaemia 
(CML)

Question 19

What is acute leukaemia?

Answer 19

→rapid onset and short but severe course

Question 20

What are characteristics of acute leukaemia?

Answer 20

→Undifferentiated leukaemia

→uncontrolled clonal and accumulation of immature white blood cells (-blast)

→High number of blasts in blood

Question 21

Which cells in the bone marrow are involved in acute leukaemia?

Answer 21

→myeloblast

→lymphoblast

Question 22

What are the characteristics of chronic leukaemia?

Answer 22

→Differentiated leukaemia

→uncontrolled clonal and accumulation of mature white blood cells (-cyte)

Question 23

Which cells in the bone marrow are involved in chronic leukaemia?

Answer 23

→-cytes

Question 24

What is the age of onset for acute and chronic Leukaemia?

Answer 24

→ acute= children

→chronic= insidious

Question 25

What is the onset like for acute and chronic leukaemia?

Answer 25

→ acute= sudden, weeks to months

→chronic= insidious, years

Question 26

What is the WBC count like in acute and chronic leukaemia?

Answer 26

→acute = Variable- high rates of blasts
→chronic= high

Question 27

What are the two types of acute leukaemia?

Answer 27

→Acute Lymphoblastic Leukaemia (ALL)- 75%

→Acute Myeloblastic Leukaemia (AML)-20%

Question 28

What are the typical symptoms of acute leukaemia due to bone marrow suppression?

Answer 28

→Thrombocytopenia: nosebleed
→Neutropenia
→anaemia
→night sweats
→frequent infections

Question 29

Which is the most common childhood cancer?

Answer 29

→Acute Lymphoblastic Leukaemia

Question 30

What is the cells classification of ALL?

Answer 30

→B-cell & T-cell leukaemia

Question 31

What is the treatment for ALL?

Answer 31

→Chemotherapy

Question 32

What is the outcome like for ALL treatment?

Answer 32

→5 year event-free survival (EFS) of 87%

→1 out of 10 ALL patients relapse.
→Remission in 50% percent of them after second chemotherapy treatment or bone marrow transplant.

Question 33

Why are adult ALL prognosis poor?

Answer 33

→because disease presents different cell of origin and different oncogene mutations.

Question 34

What is the prevalence of AML?

Answer 34

→rare in children

Question 35

How is AML classified?

Answer 35

→based on FAB system (French-American-British): M0-M7

Question 36

What are the treatments for AML?

Answer 36

→Chemotherapy,

→monoclonal antibodies (immunotherapy) +/- allogeneic bone marrow transplant.

Question 37

What is the outcome like for AML?

Answer 37

→5 year event-free survival (EFS) of 50-60%.

Question 38

How is AML and ALL differentiated in diagnosis?

Answer 38

→use cytomorphological studies

Question 39

What are the symptoms of CLL?

Answer 39

→Recurrent infections due to :
→neutropenia, 
→ anaemia, 
→thrombocytopenia, 
→lymph node enlargement, 
→hepatosplenomegaly.

Question 40

What is the treatment for CLL?

Answer 40

→Regular chemotherapy to reduce cell numbers

Question 41

What is the outcome like for CLL?

Answer 41

→5-year event-free survival (EFS) of 83%

→ Many patients survive >12 years.

Question 42

What is the peak age for CML?

Answer 42

→peak rate = 85-89y/o

Question 43

What are the symptoms of CML?

Answer 43

→Often asymptomatic

→discovered through routine blood tests.

Question 44

How is CML diagnosed?

Answer 44

→Very high white cells count (neutrophilia) in blood and bone marrow,
→presence of Philadelphia chromosome

Question 45

What is the treatment for CML?

Answer 45

→Targeted therapy: Imatinib

→allogeneic bone marrow transplant

Question 46

Why is the BCR-ABL protein an oncogene?

Answer 46

→has constitutive (unregulated) protein tyrosine kinase activity
→ABL has a strong promotor and ABL gene encodes a protein tyrosine kinase

Question 47

What does unregulated BCR-ABL tyrosine kinase activity cause?

Answer 47

→Proliferation of progenitor cells in the absence of growth factors

→Decreased apoptosis

→Decreased adhesion to bone marrow stroma

Question 48

What might a detection of minimal residual disease mean for treatment?

Answer 48

→clue as to the efficacy of treatment

Question 49

How does Imatinib work?

Answer 49

→Drugs that specifically inhibit BCR-ABL
→imatinib competes with ATP which binds to BCR-ABL fusion
→ used to detect minimal residual disease

Question 50

What are the differences between targeted therapies and chemotherapy?

Answer 50

→Targeted Act on specific molecular targets associated with cancer whereas chemotherapy Act on all rapidly dividing cells (cancerous and normal)

→targeted is cytostatic whereas chemotherapy is cytotoxic

→targeted used oral agents whereas chemotherapy is mainly intravenous with some oral agents