Leukaemia Flashcards

Question

Physical, chemical and biological agents in activation of oncogenes or mutations

Answer 1

- heredity - chromosomal abnormalities - chemical agents/drugs e.g benzene - ionising radiation - viruses

Answer 2

- 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

Answer 3

- acute lymphoblastic (lymphocytic) leukaemia (ALL) - acute myeloid (myelogenous) leukaemia (AML) - chronic lymphocytic leukaemia (CLL) - chronic myeloid leukaemia (CML)

Answer 4

- acute: made of immature blast cells - ALL most common in children - AML most common in adults - chronic have no blast cells

Answer 5

- 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

Answer 6

- 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

Answer 7

- M0 Undifferentiated - M1 AML without maturation - M2 AML with granulocytic maturation

Answer 8

- M3 Acute promyelocytic leukaemia | - M4 Myelomonocytic leukaemia

Answer 9

- M5 Monoblastic or monocytic leukaemia - M6 Erythroleukaemia - M7 Megakaryocytic leukaemia

Answer 10

- large, crystalline cytoplasmic inclusion bodies

Answer 11

- 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.

Answer 12

- 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

Answer 13

- 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

Answer 14

- 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)

Answer 15

- 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)

Answer 16

- 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

Answer 17

- 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

Answer 18

- 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

Answer 19

- Greatly increased levels of serum lysozyme are seen in monocytic leukaemias, with smaller increases seen in myeloblastic leukaemias

Answer 20

- 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

Answer 21

- L1 small, monomorphic - L2 large, heterogeneous - L3 Burkitt-cell type

Answer 22

- 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

Answer 23

- 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.

Answer 24

- 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

Answer 25

- Translocation t(9;22)(q34;q11) - The Philadelphia chromosome is 22 - This is where the ABL-BCR (tyrosine kinase) fusion is

Answer 26

- 20% of all leukaemias - 1 per 100,000 population - between 20 and 60 years of age.

Answer 27

- 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

Answer 28

- 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

Answer 29

- 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.

Answer 30

- disease of the elderly, rare in patients <40 years old | - male:female ratio of 2:1

Answer 31

- 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

Answer 32

- 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.