Haematology 2: Acute Leukaemias Flashcards
<p>Which acute leukaemia is an emergency ?</p>
<p>APML (acute promyeloid)</p>
<p>What translocation causes Acute promyelocytic leukaemia (APML), which fusion gene?</p>
<p>T(15;17)
| <br></br><br></br>Fusion gene = (PML-RARA) (promyelocytic leukemia/retinoic acid receptor alpha)</p>
<p>Which leukaemia is more common in patients with Down’s syndrome ?</p>
<p>ALL+ AML </p>
- Thought to be dose effect (they have more of the protoncogene)
<p>What signs is characteristic in APML ?</p>
<p>Sudden onset Haemorrhage (bruising and bleeding)
<br></br>
<br></br>
<br></br>This is because APML is associated w/ DIC + Hyperactive fibrinolysis</p>
<p>Which feature is characteristic of APML on microscopy ?</p>
<p>Multiple auer rods in promyelocytes</p>
<p>What does the variant of APML without auer rods look like on microscopy ?</p>
<p>Promyelocytes with Bilobed nuclei</p>
<p>Which 2 stains are possitive in AML but not In ALL ?</p>
<p>Myeloperoxidase stain<br></br>Sudan black B stain</p>
<p>Which leukaemia causes Gum infiltration ?</p>
<p>Monocytic AML</p>
<p>List 5 signs of AML ?</p>
<p>Anaemia- SOB, Pallor<br></br>Neutropenia- infections <br></br>Thrombocytopenia- easy Bruising and bleeding, DIC<br></br>Hepatosplenomegally <br></br>Retinal haemorrhage/exudates</p>
<p>What is the most important diagnostic test for Leukaemias ?</p>
<p>Immunophenotyping</p>
<p>What is the most common leukaemia in childhood ?</p>
Who else can commonly have this?
Prognosis?
<p>ALL</p>
Bimodal distribution - another peak in old age (this has higher incidence of philadelphia +ve cases) - t(9;22)
85% of children are cured, old age = poor prognosis as less likely to cope w/ chemo + philadelphia +ve is more severe
<p>List 5 signs of ALL ?</p>
<p>BM failure:
<br></br>- Anaemia- SOB, pallor
<br></br>- Neutropenia- infections
<br></br>- Thrombocytopenia- Easy bruising, bleeding
<br></br>
<br></br>Lymphadenopathy
<br></br>Hepatosplenomegaly</p>
<p>Which drug is used to treat CML or ALL with the Philadelphia chromosome abnormality ?</p>
<p>Tyrosine kinase inhibitor- Imatinib</p>
<p>Which cell level does CML tend to occur in? and AML?</p>
<p>CML:
Pluripotent haematopoietic stem cell<br></br>
AML:
Pluripotent haematopoietic stem cell or multipotent myeloid stem cell or granulocyte-monocyte precursor</p>
<p>Chromosomal abnormalities associated with AML? (5)</p>
<p>Duplications
Loss
Translocation
Inversion
Deletion</p>
<p>How can an altered DNA sequence lead to leukaemia?</p>
<p>By the creation of a fusion gene
<br></br>
<br></br>By abnormal regulation of genes</p>
<p>Which chromosomal duplications are most commonly associated with AML?</p>
<p>8 and 21 (there is a predisposition seen in Down syndrome)</p>
<p>List some molecular abnormalities that can occur in apparently normal chromosomes.</p>
<p>Point mutations
<br></br>Loss of function of tumour suppressor genes
<br></br>Partial duplication
<br></br>Cryptic deletion (formation of a fusion gene by deletion of a small section of DNA)</p>
<p>What are type 1 and type 2 abnormalities with regards to leukaemogenesis?</p>
leukaemogenesis in AML?
<p>Type 1: promote proliferation and survival (anti-apoptosis)
<br></br>
<br></br>Type 2: block differentiation
<br></br>
<br></br>NOTE: leukaemogenesis in AML requires multiple genetic hits</p>
<p>Give a type 1 and type 2 mutation for APML.</p>
<p>Type 1: FLT3-ITD (internal tandem duplication)
| <br></br><br></br>Type 2: PML-RARA</p>
<p>Give a type 1 and type 2 mutation for CBF (core binding factor) leukaemias.</p>
<p>Type 1: sometimes mutated KIT
<br></br>
<br></br>Type 2: mutations affecting function of CBF</p>
<p>Which microscopic feature is pathognomonic of myeloid leukaemias?</p>
<p>Auer rods</p>
<p>What is aleukaemic leukaemia?</p>
<p>When there are no leukaemic cells in the peripheral blood but the bone marrow has been replaced</p>
<p>What is a key difference in the origin of B-lineage and T-lineage ALL?</p>
<p>B-lineage starts in the bone marrow (85%)
| <br></br><br></br>T-lineage can start in the thymus (which may be enlarged) (15%)</p>
<p>How long does chemotherapy for ALL usually take? Why is it longer in boys?</p>
<p>2-3 years
<br></br>
<br></br>Longer in boys because the testes are a site of accumulation of lymphoblasts
<br></br>
<br></br>NB. can also accumulate in CNS</p>
<p>What are the four phases of chemotherapy for ALL?</p>
<p>Remission induction
Consolidation and CNS therapy
Intensification
Maintenance</p>
<p>Who receives CNS-directed chemotherapy? How can this be given?</p>
<p>All patients should receive CNS-directed chemotherapy
<br></br>
<br></br>This can be given intrathecally or a high dose of chemotherapy could be given such that it penetrates the BBB</p>
<p>Recall some clinical signs that can be used to identify AML</p>
Hepatosplenomegaly
Monocytic gum infiltration
CNS disease
Occasional lymphadenopathy
<p>What is the most effective investigation for differentiating AML and ALL, and what results would it show for each?</p>
<p>Immunophenotyping:<br></br>
AML: CD13/14/15<br></br><br></br>
ALL: CD3/4/18/19/20</p>
<p>Recall some useful supportive therapies for AML</p>
Blood products: red cells, platelets and FFP
Antibiotics
Long line
Allopurinol (as uric acid may be released from dying cells when treatment is started)
<p>Recall some sites of leukaemic involvement in ALL that you wouldnt see in AML</p>
<p>Thymus, testes, CNS</p>
<p>Which type of leukaemia is most likely to present with long bone pain?</p>
<p>ALL</p>
What are 3 ways of differentiating between AML and ALL?
Cytological features
Cytochemistry
Immunophenotyping
Cytological differences between AML and ALL?
AML:
- Abundant amount of cytoplasm w/ granules present
- Coarse chromatin appearance due to granules
- 3-4 nuclei
- Auer rods present
ALL:
- A rim of cytoplasm w/out chromatin
- Fine chromatin appearance
- 1-2 nuclei
- No auer rods
Cytochemistry in ALL v AML?
Not used as much anymore however stains used are:
Myeloperoxidase - MAIN
Sudan black
Non-specific esterase
These are all positive in AML but not ALL
Prognosis for APML w/ treatment + what treatment?
Good prognosis when treated w/ All-trans retinoic acid (high dose vit A)
ATRA
Acute leukaemia + t(9;22) + CD19 and TdT =?
ALL - t(9;22) present in 30%
