Leukaemia Flashcards
1
Q
Neoplasm
A
- abnormal new growth
2
Q
Benign tumour
A
- remain localised, don’t metastasize
3
Q
Malignant tumour
A
- metastasize through lymphatic channels or blood vessels to lymph nodes and other tissues in the body
4
Q
Primary tumour
A
- tumour growing at the anatomical site where tumour progression began and proceeded to yield this mass
5
Q
Metastatic tumour
A
- tumour forming at one site in body, cells (metastases) of
which derive from a tumour located elsewhere in the body
6
Q
Carcinomas
A
- constitute 90% of cancers
- cancers of epithelial cells
7
Q
Sarcomas
A
- rare and consist of tumours of connective tissues (connective tissue, muscle, bone etc.)
8
Q
Leukaemias and lymphomas
A
- constitute 8% of tumours
- aka liquid tumours
- leukaemias arise from blood forming cells
- lymphomas arise from cells of the immune system (T and B cells)
9
Q
Proto-oncogenes
A
- over 100
- proteins that promote cell cycle
- mutations lead to oncogenes, promote cell growth regardless of circumstances
10
Q
Tumour suppressor genes
A
- proteins that inhibit cell cycle
- mutations lead to cell cycle not stopping even when it should (p53 and Rb genes)
11
Q
DNA repair genes and apoptosis genes
A
- DNA repair genes repair any mutated genes
- apoptosis genes kill mutated genes
12
Q
Proto oncogenes that code for leukaemia
A
- BCR-ABL (tyrosine kinase)
- MYC (transcription factor)
13
Q
Tumour suppressor genes that codes for leukaemia
A
- NF-1
- inhibitor of Ras, a protein that stimulates cell division
14
Q
Leukaemia vs Lymphoma
A
- Leukaemia: neoplasm originates from haemopoietic stem cells in bone marrow w/widespread movement in peripherical blood
- Lymphoma: neoplasm originates from lymphocytes, which are in lymph nodes, spleen, thymus and bone marrow
15
Q
Symptoms of leukaemia
A
- weight loss
- fever
- frequent infections
- shortness of breath
- muscular weakness
- pain/tenderness in bones or joints
- fatigue
- loss of appetite
- swelling of lymph nodes
- spleen/liver enlargement
- night sweats
- easy bruising
- purplish patches or sports
16
Q
Malignant haematopoiesis
A
- cell of origin of leukaemia undergoes mutations
- become leukaemia stem cells
- block in differentiation causes them to divide and become blasts
17
Q
Oncogenic drivers of granulocyte macrophage progenitor
A
- MLL-ENL
- MLL-AF9
- MOZ-TIF2
18
Q
Oncogenic drivers of common myeloid progenitor
A
- MLL-ENL
- MLL-AF9
- MOZ-TIF2
- MN1
19
Q
Oncogenic drivers of common lymphoid progenitor
A
- MLL-ENL
- MLL-AF9
20
Q
Oncogenic drivers from haematopoietic stem cell
A
- MLL-ENL
- MLL-AF9
- MOZ-TIF2
- MN1
- CALM-AF10
- MLL-GAS7
21
Q
General mechanisms of leukemic transformation
A
- impaired differentiation
- increased cell survival
- increased proliferation
- increased self-renewal
- genomic instability
22
Q
Metastasis of leukaemia
A
- Leukaemia-derived exosomes transfer pro-angiogenic molecules toward ECs
- enhances angiogenesis through stimulating factors
- Leukemic cells-derived exosomes cause metastasis
to lymph nodes through blood circulation
23
Q
Leukaemia clonal disorder
A
- Haematological malignancies are clonal disorders
- the malignant cells all share the same basic genetic or molecular abnormalities
24
Q
Key genetic/biochemical steps in leukaemia (aetiology)
A
- genetic mutation/oncogene activation leading to
- increased proliferation rate
- reduced apoptosis
- block in differentiation
25
Q
Physical, chemical and biological agents in activation of oncogenes or mutations
A
- heredity
- chromosomal abnormalities
- chemical agents/drugs e.g benzene
- ionising radiation
- viruses
26
Q
Chromosomal abnormalities in leukaemia
A
- deletions: deletion of entire, or part of, a chromosome, therefore effect on cell function
- inversions: rearrangement in which a segment of a chromosome is reversed
- translocations: exchange of genetic material between chromosomes
27
Q
Four main types of leukaemia
A
- acute lymphoblastic (lymphocytic) leukaemia (ALL)
- acute myeloid (myelogenous) leukaemia (AML)
- chronic lymphocytic leukaemia (CLL)
- chronic myeloid leukaemia (CML)
28
Q
Acute (ALL and AML) vs Chronic (CLL and CML) leukaemias
A
- acute: made of immature blast cells
- ALL most common in children
- AML most common in adults
- chronic have no blast cells
29
Q
General features of leukaemia
A
- most common neoplastic disease of white cells
- 9 per 100,000 population
- expansion of bone marrow + infiltration by neoplastic white cells is common
- neoplastic proliferation of marrow cells forming one or more cell lines.
- Circulation of neoplastic cells in peripheral blood in most cases.
- Anaemia
- Low platelets
- Bone marrow appearance becomes ‘monotonous’ as it is replaced by abnormal cells
30
Q
Acute leukaemias
A
- uncontrolled proliferation of poorly differentiated blast cells (>20%)
- marrow replacement by blast cells causes anaemia, increase in infection, and an increased tendency towards bleeding.
- Patients develop fever, malaise, bleeding and mouth ulcers due to infections.
- increased white cell count (including blast cells) in about 50% of cases. Could also be normal or reduced
• Diagnosis is based on the bone marrow aspirate.
• frequently show infiltration of many organs, especially the brain
31
Q
French-American-British (FAB) Scheme of Classification of AML (M0, M1, M2)
A
- M0 Undifferentiated
- M1 AML without maturation
- M2 AML with granulocytic maturation
32
Q
French-American-British (FAB) Scheme of Classification of AML (M3, M4)
A
- M3 Acute promyelocytic leukaemia
- M4 Myelomonocytic leukaemia
33
Q
French-American-British (FAB) Scheme of Classification of AML (M5, M6, M7)
A
- M5 Monoblastic or monocytic leukaemia
- M6 Erythroleukaemia
- M7 Megakaryocytic leukaemia
34
Q
Auer rods
A
- large, crystalline cytoplasmic inclusion bodies
35
Q
Bone marrow failure in acute leukaemias
A
- pallor and lethargy, due to reduction in erythropoiesis.
- Fever, malaise, infections of the mouth, throat, skin and respiratory tract - due to
the reduction in production of normal WBC’s. - Spontaneous bruising, purpura, bleeding gums etc, usually due to
thrombocytopaenia.
36
Q
Organ infiltration in acute leukaemias
A
- Bone pain.
- Lymphadenopathy in ALL
- Moderate splenomegaly and hepatomegaly, especially in ALL
- Infiltration of the gums and skin is particularly seen in myelomonocytic (M4) and
monocytic (M5) types
37
Q
Lab findings in acute leukaemias
A
- Normochromic, normocytic anaemia
- Total WBC count may be decreased or normal but it is often increased to >200 x 10^9
/l, with variable numbers of blast cells. - In AML the blast cells may contain Auer Rods.
- Thrombocytopaenia is present in most acute leukaemias, and is marked in AML.
- Hypercellularity of the bone marrow
38
Q
Chloroacetate esterase in acute leukaemias
A
- leucocyte isoenzymes of esterases 1,2,7 and 8 can be stained using a-naphthyl AS-D chloroacetate.
- main application of this stain is in the differentiation of granulocytic cell lines (CE positive) and monocytic cell lines (negative)
39
Q
Peroxidase and Sudan Black B
A
- Peroxidase is for myeloperoxidase which is
present in granulocyte and monocyte cell lines.
• Sudan Black B stains neutral fats, phospholipids and lipoprotein and the reaction
patterns are closely equivalent to the peroxidase reaction. - These stains are therefore most useful in distinguishing between ALL and AML (M1
- M6)
40
Q
Non-specific esterase in acute leukaemias
A
- many substrates which can be used to identify and localise isoenzymes of esterases 3,4,5, and 6.
- main use of this stain is to differentiate between granulocytic and monocytic cell lines.
- monocytic cell lines are NSE positive
41
Q
Acid phosphatase in acute leukaemias
A
- Acid phosphatase is present in lysosomes of haemopoietic cells.
- The most significant application isthe classification of lymphoproliferative diseases.
- In T- cell ALL the reaction is localised to an area of the cytoplasm which is occupied by the Golgi apparatus
42
Q
Terminal deoxynucleotidyl transferase (TdT) in acute leukaemias
A
- TdT is a DNA polymerase activity which is present at high levels in lymphoid cells.
- It is an early marker for B and T cell acute lymphoblastic leukaemia
43
Q
Lysozyme in acute leukaemias
A
- Greatly increased levels of serum lysozyme are seen in monocytic leukaemias, with smaller increases seen in myeloblastic leukaemias
44
Q
Immunological markers in acute leukaemias
A
- particularly used in identification of subgroups of ALL presence or absence of cell surface marker molecules.
- The advent of McAbs has allowed identification of cells at varying stages of their
differentiation
45
Q
FAB classification of ALL
A
- L1 small, monomorphic
- L2 large, heterogeneous
- L3 Burkitt-cell type
46
Q
Acute Lymphoblastic Leukaemia (ALL)
A
- Accumulation of lymphoblasts in bone marrow
- Incidence of ALL is highest at 3–7 years
- Some cases initiated by genetic mutations that occur during development in utero
47
Q
Chronic leukaemias
A
- malignant cells are relatively well differentiated
- Identifiable morphologically by the use of conventional Romanowski staining procedures.
- 2 major classifications of chronic leukaemia are CML and CLL.
48
Q
Chronic myeloid leukaemia (CML)
A
- aka chronic granulocytic leukaemia CGL.
- malignant proliferation of granulocytes in bone marrow and other haemopoietic organs
- characterised by the presence of a chromosomal marker, the Philadelphia (Ph) chromosome, in the haemopoietic cells
49
Q
Philadelphia chromosome
A
- Translocation t(9;22)(q34;q11)
- The Philadelphia chromosome is 22
- This is where the ABL-BCR (tyrosine kinase) fusion is
50
Q
Incidence of CML
A
- 20% of all leukaemias
- 1 per 100,000 population
- between 20 and 60 years of age.
51
Q
Clinical features of CML
A
- Anaemia: pallor, lethargy, especially in the later stages
- Splenomegaly and hepatomegaly - former is almost always present and often massive, latter is fairly common.
- Bleeding: haemorrhage or bruising is common, due to abnormal platelet function.
- Hypermetabolism: an increase in the basal metabolic rate is common, resulting in fever, night sweats and weight loss.
- Bone pain - hypercellularity of marrow.
- Prolonged infections
52
Q
Lab findings in CML
A
- Normochromic/normocytic anaemia
- WBC count between 50-300 x10^9/l, but may be higher
- A complete range of myeloid cells seen in the peripheral blood, majority of cells being myelocytes, metamyelocytes, band forms and mature
neutrophils - A few myeloblasts and promyelocytes may be seen
53
Q
Features in CML
A
- Thrombocytosis common in the early stages, platelet counts of >1000 x10^9/l may be reached
- platelets are larger than normal and reduced function.
- Hypercellularity of marrow, with many cells of granulocyte series.
- most cases show increased level of LDH. Serum B12 levels may be up to 15x normal level, due to increased synthesis of
transcobalmins I and III by leukaemic granulocytes. - Philadelphia Chromosome: Chromosomal analysis of
haemopoietic cells reveals the Ph chromosome. - An abnormally small chromosome which results from translocation of a portion of the long arm of ch 22 to
ch 9. This is considered as a diagnostic indicator of
CML.
54
Q
Incidence of CLL
A
- disease of the elderly, rare in patients <40 years old
- male:female ratio of 2:1
55
Q
Clinical features of CLL
A
- Anaemia isn’t an obvious symptom in most cases, especially in the early stages
- About 10% of casesdevelop an haemolytic anaemia
- Splenomegaly and hepatomegaly are common
- Lymphadenopathy.
- Bruising and purpura - due to thrombocytopaenia
- Infections are common: bacterial, fungal, viral infections may present
56
Q
Lab findings of CLL
A
- anaemia may be present later
- 10% of cases develop autoimmunity.
- Total WBC is >15 x 10^9/l and may be 300 x 10^9/l or higher.
- Between 70-99% of cells are small mature lymphocytes.
- Smear cells are common, fragile cells which are disrupted when making the blood film.
- mature cells are B-cells in 90% of cases.
- relatively rare T-CLL tends to be much more aggressive
- Thrombocytopaenia - usually in later stages
- bone marrow biopsy isn’t usually required for diagnosis, marrow is 30-50% infiltrated by lymphocytes.
