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Intro to leukaemia Flashcards

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1
Q

What is leukaemia?

A

Malignant disorders of haematopoietic stem cells characteristically associated with increased number of white cells in bone marrow or/and peripheral blood

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2
Q

What is leukemia categorised by?

A

• Categorised by distorted proliferation and development of leukocytes and precursors in bone marrow and peripheral blood

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3
Q

Why is leukemia a clonal disease?

A

§ Oncogenic TFs drive cell progenitors to pre-leukaemic state
§ Will arrest differentiation and maturation of those progenitor cells
§ Second hit will induce full blown leukaemia that will cause reduced apoptosis and increased proliferation

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4
Q

What can pluripotent hematopoietic stem cells give rise to?

A

-Can give rise to cells of every blood lineage e.g. the common myeloid and common lymphoid progenitors

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5
Q

How are hematopoietic stem cells self-maintaining?

A

○ Stem cell can divide to produce more stem cells

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6
Q

What are the 2 types of progenitor cells?

A
  1. Undifferentiated

2. Committed

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7
Q

Undifferentiated progenitor cells

A

E.g. myeloblast, lymphoblast
§ Are multipotent
§ Can divide to produce many mature cells
§ But cannot divide indefinitely
§ Eventually differentiate and mature
§ Cannot tell difference between progenitors morphologically because they do not show characteristics of mature cells

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8
Q

Committed progenitor cells

A

§ Unipotent

§ Already committed as to what they will become when they generate into mature cells

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9
Q

What is the presentation of leukemia?

A

• First presents with symptoms due to loss of normal blood cell production
○ Abnormal bruising-commonest
§ Due to abnormal production of platelets
○ Repeating abnormal infection
○ Sometimes anaemia
§ Due to low iron in the blood

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10
Q

What is a polyetiologic disease?

A

Combination of predisposing factors, mainly genetic and environment but others including lifestyle related factors

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11
Q

What is leukemia caused by?

A

Caused by somatic mutations

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12
Q

What may predispose to leukemia?

A

Some rare genetic diseases may predispose to leukaemia

-Downs syndrome

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13
Q

What gene mutations may cause leukemia?

A

Gene mutations involving oncogenes (activation) and/or tumour suppressors (inactivation)

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14
Q

What happens to the RAAS pathway in leukaemia?

A

RAAS pathway is usually mutated in leukaemia

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15
Q

What are the chromosome aberrations in leukemia?

A

○ Translocations (e.g. BCR-ABL in CML and PML-RAR in AML)

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

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16
Q

What are environmental risk factors that can cause leukaemia?

A
  • Radiation exposure
  • Exposure to chemicals and chemotherapy
  • Immune system suppression
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17
Q

What are the lifestyle related risk factors that can cause leukaemia?

A

○ Smoking
○ Drinking
○ Excessive exposure to sun
○ Overweight

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18
Q

What are the controversial risk factors that cause leukaemia?

A
  • Exposure to electromagnetic fields i.e. during pregnancy
  • Infection early in life
  • Mother’s age when child is born
  • Nuclear power stations
  • Parents smoking history
  • Fetal exposure to hormones
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19
Q

What is an acute disease?

A

rapid onset and short but severe course

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20
Q

What is acute leukaemia?

A

§ Undifferentiated leukaemia

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21
Q

What is acute leukaemia characterised by?

A

Characterised by uncontrolled clonal accumulation of immature white cells

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22
Q

What is a chronic disease?

A

persisting over a long time

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23
Q

What is chronic leukaemia?

Study These Flashcards
A

○ Differentiated leukaemia

24
Q

What is chronic leukaemia characterised by?

Study These Flashcards
A

Characterised by uncontrolled clonal accumulation of mature white blood cells

25
What are the typical symptoms in acute leukaemia and due to what?
○ Thrombocytopenia: purpura (bruising), epistaxis (nosebleed), bleeding from gums ○ Neutropenia: Recurrent infections, fever ○ Anaemia: lassitude, weakness, tiredness, shortness of breath This is due to bone marrow suppression
26
What is the diagnosis for acute leukaemia?
○ Peripheral blood blasts test: to check for presence of blasts and cytopenia ○ Bone marrow test/biopsy: taken from pelvic bone, >30% blasts is diagnostic of acute leukaemia ○ Lumbar puncture: to determine if the leukaemia has spread to the cerebral spinal fluid (CSF)
27
What do we see in the blood sample for acute lymphoblastic leukaemia?
○ In blood sample there will be many blasts 
28
What is the classification of acute lymphoblastic leukaemia?
• Classification: B-cell & T-cell leukaemia
29
What is the treatment for acute lymphoblastic leukaemia?
Chemotherapy
30
What is acute lymphoblastic leukaemia a cancer of?
A cancer of immature lymphocytes
31
What is acute myeloblastic leukaemia a cancer of?
• Cancer of immature myeloid white blood cells
32
What is the classification of acute myeloblastic leukaemia based on?
Classification based on FAB system: - Based on stages of differentiation - And cell type
33
What is the treatment for acute myeloblastic leukaemia?
- Chemotherapy | - Monoclonal antibody
34
What is chronic leukaemia characterised by?
Characterised by an increase number of differentiated cells -differentiated leukaemia
35
What does chronic lymphocytic leukaemia have a large number of?
• Large numbers of mature (clonal) lymphocytes in bone marrow and peripheral blood
36
What are the symptoms of chronic lymphocytic leukaemia?
``` ○ Recurrent infections due to neutropenia, and suppression of normal lymphocyte function ○ Anaemia ○ Thrombocytopenia ○ Lymph node enlargement ○ Hepatosplenomegaly ```
37
What is the treatment for chronic lymphocytic leukaemia?
○ Controlled by regular chemotherapy to reduce cell numbers 
38
What does chronic myeloid/granulocytic leukaemia have a large number of?
• Large numbers of mature myeloid white blood cells.
39
What are the symptoms of chronic myeloid/granulocytic leukaemia?
○ Often asymptomatic and discovered through routine blood tests; anaemia; fatigue; breathlessness; splenomegaly; LU quadrant fullness or pain; weight loss; and other less common
40
What is the diagnosis of chronic myeloid/granulocytic leukaemia?
○ Very high WBC count (neutrophilia)in blood and bone marrow  ○ Presence of Philadelphia chromosome or BCR-ABL gene rearrangements 
41
What is the treatment of chronic myeolid/granulocytic leukaemia?
Controlled but not cured with chemotherapy. Imatinib.
42
What is a philadelphia chromosome and how does it form?
Balanced translocation between long arms of chromosome 9 and 22  ○ In long arm of Chr9, there will be a part that will be translocated and exchanged with Chr22  ○ Chr22 will be called a Philadelphia chromosome 
43
What does BCR usually encode?
Usually encodes a protein that acts as a guanine nucleotide exchange factor for Rho GTPase proteins
44
What does ABL usually encode?
Usually encodes a protein tyrosine kinase whose activity is tightly regulated
45
How does BCR control ABL??
○ When BCR and ABL come together, the activity levels will be very high as ABL gene will lose the first part of gene (promotor) that was essential for the auto-inhibition of the protein ○ This is now controlled by promotor of BCR gene  ○ BCR controls ABL  -BCR-ABL protein has constitutive (unregulated) protein tyrosine kinase activity
46
What does unregulated BCR-ABL do and cause?
It results in tyrosine activity which causes: ○ Proliferation of progenitor cells in the absence of growth factors ○ Decreased apoptosis ○ Decreased adhesion to bone marrow stroma
47
What percentage of CML cases have a detectable philadelphia chromosome?
○ 95% of cases of CML have a detectable Ph' chromosome
48
What are the therapies available for leukaemia?
§Chemotherapy §Targeted therapy §Stem cell and bone marrow transplant
49
What does chemotherapy attack?
• Attacks all rapidly dividing cells 
50
What is used for the treatment of AML and how does it work?
• Cytosine arabinoside (ara-C, cytarab) for treatment of AML ○ Cytosine analogue ○ Interferes with deoxynucleotide synthesis ○ Prevents successful DNA replication
51
What treatment is used for all leukaemias and how does it work?
• Vincristine for treatment of ALL ○ Binds to tubulin dimers ○ Inhibiting microtubule formation ○ So blocking the mitotic spindle
52
What are used in targeted therapy?
Tyrosine kinase inhibitors
53
What is used in the treatment of CML and how does it work?
• Tyrosine kinase inhibitors for treatment of CML ○ Inhibits BCR-ABL but not most other tyrosine kinases ○ Causes apoptosis of CML cells
54
What can happen to some patients from targeted therapy?
• Some patients become drug resistant
55
What are SCBMTS used mainly for ?
• Used mainly for treatment of AML
56
What happens in SCBMTS?
Haemopoiesis is reconstituted from the quiescent stem cell pool

Haematology (6 decks)

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