L25: Intro To Leukaemia Flashcards

1
Q

Define leukaemia

A

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

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2
Q

What are the two features of haematopoietic stem cells?

A

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

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

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3
Q

What are the three features of progenitor cells?

A

→Can divide to produce many mature cells

→But cannot divide indefinitely

→Eventually differentiate and mature

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4
Q

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

A

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

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5
Q

What is meant by leukaemia being clonal?

A

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

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6
Q

What are the first symptoms of all leukaemia?

A

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

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7
Q

What are the three ways of diagnosing leukaemia?

A

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

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8
Q

Why is peripheral blood test used in leukaemia diagnosis?

A

→looks for blasts and cytopenia.

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

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9
Q

Where is bone marrow taken from?

A

→taken from pelvic bone and results compared with PB.

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10
Q

Why is lumbar puncture used in leukaemia diagnosis?

A

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

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11
Q

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

A
→Cytomorphology
→Immunophenotyping
→Next Generation Sequencing (NGS)
→Flow cytometry
→Fluorescence in situ Hybridation (FISH)
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12
Q

What type of leukaemia are sometimes hereditary?

A

→Chronic Lymphocytic Leukaemia (CLL)

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13
Q

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

A

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

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

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14
Q

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

A

→Ataxia-telangiectasia,

→Wiskott-Aldrich syndrome

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15
Q

What are some genetic mutations that predisposes to leukaemia?

A

→TP53- Li-Fraumeni syndrome,

→NF1-Neurofibromatosis

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16
Q

What are some environmental risk factors that predisposes to leukaemia?

A

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

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17
Q

What are some risk factors linked to childhood leukaemia?

A
→Exposure to electromagnetic fields
→Foetal exposure to hormones
→Parent’s smoking history
→Infections early in life
→Mother’s age when child is born
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18
Q

What are the classifications of leukaemia?

A
→Acute Lymphoid Leukaemia (ALL)
→Acute Myeloid Leukaemia (AML)
→Chronic Lymphoid Leukaemia 
(CLL)
→Chronic Myeloid Leukaemia 
(CML)
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19
Q

What is acute leukaemia?

A

→rapid onset and short but severe course

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20
Q

What are characteristics of acute leukaemia?

A

→Undifferentiated leukaemia

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

→High number of blasts in blood

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21
Q

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

A

→myeloblast

→lymphoblast

22
Q

What are the characteristics of chronic leukaemia?

A

→Differentiated leukaemia

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

23
Q

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

24
Q

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

A

→ acute= children

→chronic= insidious

25
What is the onset like for acute and chronic leukaemia?
→ acute= sudden, weeks to months | →chronic= insidious, years
26
What is the WBC count like in acute and chronic leukaemia?
``` →acute = Variable- high rates of blasts →chronic= high ```
27
What are the two types of acute leukaemia?
→Acute Lymphoblastic Leukaemia (ALL)- 75% | →Acute Myeloblastic Leukaemia (AML)-20%
28
What are the typical symptoms of acute leukaemia due to bone marrow suppression?
``` →Thrombocytopenia: nosebleed →Neutropenia →anaemia →night sweats →frequent infections ```
29
Which is the most common childhood cancer?
→Acute Lymphoblastic Leukaemia
30
What is the cells classification of ALL?
→B-cell & T-cell leukaemia
31
What is the treatment for ALL?
→Chemotherapy
32
What is the outcome like for ALL treatment?
→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.
33
Why are adult ALL prognosis poor?
→because disease presents different cell of origin and different oncogene mutations.
34
What is the prevalence of AML?
→rare in children
35
How is AML classified?
→based on FAB system (French-American-British): M0-M7
36
What are the treatments for AML?
→Chemotherapy, | →monoclonal antibodies (immunotherapy) +/- allogeneic bone marrow transplant.
37
What is the outcome like for AML?
→5 year event-free survival (EFS) of 50-60%.
38
How is AML and ALL differentiated in diagnosis?
→use cytomorphological studies
39
What are the symptoms of CLL?
``` →Recurrent infections due to : →neutropenia, → anaemia, →thrombocytopenia, →lymph node enlargement, →hepatosplenomegaly. ```
40
What is the treatment for CLL?
→Regular chemotherapy to reduce cell numbers
41
What is the outcome like for CLL?
→5-year event-free survival (EFS) of 83% | → Many patients survive >12 years.
42
What is the peak age for CML?
→peak rate = 85-89y/o
43
What are the symptoms of CML?
→Often asymptomatic | →discovered through routine blood tests.
44
How is CML diagnosed?
→Very high white cells count (neutrophilia) in blood and bone marrow, →presence of Philadelphia chromosome
45
What is the treatment for CML?
→Targeted therapy: Imatinib | →allogeneic bone marrow transplant
46
Why is the BCR-ABL protein an oncogene?
→has constitutive (unregulated) protein tyrosine kinase activity →ABL has a strong promotor and ABL gene encodes a protein tyrosine kinase
47
What does unregulated BCR-ABL tyrosine kinase activity cause?
→Proliferation of progenitor cells in the absence of growth factors →Decreased apoptosis →Decreased adhesion to bone marrow stroma
48
What might a detection of minimal residual disease mean for treatment?
→clue as to the efficacy of treatment
49
How does Imatinib work?
→Drugs that specifically inhibit BCR-ABL →imatinib competes with ATP which binds to BCR-ABL fusion → used to detect minimal residual disease
50
What are the differences between targeted therapies and chemotherapy?
→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