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3rd Year Biomed > Haematology (Haematological malignancies) > Flashcards

Haematology (Haematological malignancies) Flashcards

1
Q

What are the 4 main concequences of oncogenic mutations in blood stem cells?

A

1) Failure to produce effector cells
2) Accumulation of cells at a particular stage of maturation
3) An increased cellular proliferation rate
4) A failure of apoptosis to regulate cell numbers

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2
Q

What are the 5 types of haematological malignancies?

A

1) Leukemias
2) Lymphomas
3) Multiple myeloma
4) Myelodysplastic syndromes
5) Myeloproliferative disorders

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3
Q

What is leukaemia? What cells are affected?

A

Presence of malignant haematopoietic cells within the peripheral blood or bone marrow

Can be myeloid (RBCs, neutrophils, monocytes, eosinophils, basophils, platelets or their precursors) or lymhphoid (B or T cells, plasma cells, NK cells or their precursors))

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4
Q

Describe the characteristics of both acute and chronic leukemia

A

Acute:

  • Lymphoblastic
  • Accumulation of immature blasts (>20%)
  • Aggressive, rapid onset of death

Chronic:

  • Lymphocytic
  • Lower blast accumulation (<20%)
  • More differentiated
  • Cells accumulate due to deregulation of apoptosis
  • less aggressive
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5
Q

What is lymphoma?

A

Malignancy of lymphoid cells, largely restricted to lymphoid organs

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6
Q

What is the leukaemic stage of lymphoma?

A

Rare, tumour cells overspill into bone marrow or peripheral blood

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7
Q

What 2 categories can lymphoma be split into?

A

High grade or low grade based on rate of growth

- low grade more difficult to treat

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8
Q

What is Hodgkin lymphoma?

A

Associated with mutated B cell lineage known as the Hodgkin and Reed-Sternberg cell

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9
Q

What is Non-Hodgkin lymphoma?

A

Diverse group of solid lymphoid tumours

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10
Q

What is Multiple Myeloma?

A
  • Malignancy associated with old age
  • Hyperproliferation of plasma cells that reside in bone marrow
  • Results in myelosuppression and activation of osteoclast
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11
Q

How may multiple myeloma cause kidney damage?

A

Antibodies secreted in large amounts - formation of macromolecular complexes which can damage kidneys

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12
Q

What is myelodysplastic syndrome?

A
  • Range of heterogenous blood diseases restricted to myeloid lineage
  • Associated with increased precurosrs in bone marrow (hypercellularity) with reduced numbers in the peripheral blood (cytopenia)
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13
Q

What is the result of myelodysplastic syndrome?

A
  • Subject to infections
  • may exhibit refractory macrocytic anemia (enlarged RBCs with reduced haemaglobin, not treatable with folate or iron)
  • Increased risk of acute leukemia
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14
Q

What are myeloproliferative disorders?

A

Range of conditions affecting myeloid lineage

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15
Q

Name the 3 main myeloproliferative disorders

A

1) Polycythaemia
- proliferation of RBC precursors

2) Myelofibrosis
- proliferation of fibroblasts

3) Thrombocythaemia
- proliferation of megakaryocytes resulting in increased platelet count

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16
Q

What are the 3 main types of chromosome abnormalities associated with leukemia and lymphoma?

A

Translocation
Deletion
Inversion

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17
Q

Give an example of a translocation that results in leukemia

A

Reciprocal translocation between chromosome 9 and 22 creating the BCR-ABL fusion gene

  • Philadelphia chromosome
  • CML
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18
Q

What are Interstitial deletions, terminal deletions and microdeletions?

A

Interstitial - a deletion within a chromosome

Terminal - deletion at a chromosome tip

Microdeletions - small deletions that may be undetectable in a karyotype but may still be associated with malignancy

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19
Q

What are paracentric and pericentric inversions?

A

Paracentric - restricted to single arm
Pericentric - involves the centrosome

(see diagram on slide 9)

20
Q

Describe the karyotype of both a male and a female with chronic lymphocytic leukaemia (CLL)

A

Male:

  • Additional chromosome 12 (trisomy)
  • Deletion of long arm of chromosome 13

Female:

  • Trisomy 3 and 18
  • Translocation from chromosome 7 to 11
21
Q

What is epigenetics?

A

The study of alterations in gene expression

22
Q

Give some examples of epigenetic modifications to nucleic acids

A

1) Hypermethylation - adding methyl groups, suppresses transcription
2) Hypomethylation - removal of methyl groups, increases oncogene expression
3) Acetylation (of histones)
4) Phosphorylation
5) Ubiquitination (of histones)

23
Q

How does DNA methylation cause transcriptional repression?

A

1) Methylation of cytosine within promoter CpG island allows assembly of inhibitory complex involving histone deacetylase and sin3a
2) Complex causes chromatin remodelling by deacetylating histone h3 and h4 lysine residues
3) Activators that normally bind acetylated lysine fail to do so
4) Transcriptional repression

24
Q

Are DNA methyltransferases over or under expressed in many haematological malignancies?

A

Over expressed

25
Q

How do haematological malignancies grow and mutate?

A

By clonal evolution

26
Q

What are the 3 main causes of genetic changes resulting in haematological malignancies?

A

1) Inheritance
2) Environmental
3) Infection

27
Q

Give an example of an inherited syndrome that increases the incidence of haematological malignancy

A

Trisomy 21 (Downs Syndrome)

28
Q

Give an example of an environmental factor that can increase the incidence of haematological malignancy?

A

Ionising radiation

29
Q

Give some examples of infectious agents that can cause haematological malignancies

A

1) EBV
2) Human T-lymphotrophic virus (HTLV-1)
3) Human herpesvirus 8
4) Helicobacter pylori

30
Q

What is the very first investigation of haematological malignancy?

A

Patient presentation (assessing symptoms)

31
Q

What are some symptoms of haematological malignancies?

A
  • Lethargy
  • Recurrent infections
  • Easy brusing
  • Night sweats
  • Flu like symptoms
  • enlarged spleen and/or liver
32
Q

What will the first test likely be?

A

Full blood count

- limited value, some malignancies do not change measures of cell number

33
Q

Why may a blood film be used?

A

Do identify dysplasia (abnormal development)

34
Q

What is a leucoerytheoblastic blood picture?

A

A blood film with immature red or white cells

35
Q

Why is a bone marrow assessment essential?

A
  • To asses the cellularity of the sample e.g normo-, hyper, or hypo cellular
  • Comparison of cells in biopsy to a normal range
36
Q

How is cytochemistry used in heamotological malignancy testing?

A

Use of microscopic techniques to assess the characterstics of cells following a range of cytochemical stains

37
Q

What is the problem with cytochemistry?

A

Can be difficult to differentiate between myeloblasts and lymphoblasts
- may result in misclassification of the malignancy

38
Q

What is immunophenotyping also known as? What has it largely replaced?

A

Flow cytometry

Largely replaced cytochemistry

39
Q

What are the Bethesda Group recommendations for immunophenotyping?

A

Suggests cases where immunophenotyping should or shouldnt be used
For example:
Used for atypical cells or blasts present in the blood or bone marrow
Not used for basophilia, mature neutrophilia etc

40
Q

How is immunophenotyping performed?

A

Monoclonal antibodies that bind to specific antigens are labelled with fluorochrome

Flow cytometer uses laser and detector to assess whether antibody has bound

41
Q

What do forward scatter and side scatter measure?

A

Forward (x-axis): measures the size of the cells - further to the right = larger

Side scatter (y-axis) - measures internal complexity e.g granularity - the more complex, the higher up the axis

Colours represent different surface antigen e.g CD33 in AML

Example: Neutrophils are large and granular, so appear top right

42
Q

What is cytogenetic analysis?

A

A fusion of cytology (study of cells) and genetics

43
Q

What information may cytogenetics provide about haematological malignancies?

A
  • Diagnosis
  • Selection of optimal therapeutics
  • Info on prognosis
  • monitoring of disease progression
44
Q

What cytogenetic analysis will be used first?

A

A karyotype to identify chromosome abnormalities in addition to Fluorescent in situ hybridisation (FISH)

45
Q

When are these techniques not very useful?

A

When the genetic changes are minimal e.g. microdeletions or point mutations

46
Q

What is used in the case of minimal genetic changes?

A

Molecular techniques such as PCR, DNA sequencing, microarray gene expression study

3rd Year Biomed (44 decks)

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