Haematology 2: Acute Leukaemias Flashcards
(37 cards)
<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>
How long does chemotherapy for ALL usually take? Why is it longer in boys?
2-3 years
Longer in boys because the testes are a site of accumulation of lymphoblasts
NB. can also accumulate in CNS
What are the four phases of chemotherapy for ALL?
Remission induction Consolidation and CNS therapy Intensification Maintenance
Who receives CNS-directed chemotherapy? How can this be given?
All patients should receive CNS-directed chemotherapy
This can be given intrathecally or a high dose of chemotherapy could be given such that it penetrates the BBB
Recall some clinical signs that can be used to identify AML
What is the most effective investigation for differentiating AML and ALL, and what results would it show for each?
Immunophenotyping:
AML: CD13/14/15
ALL: CD3/4/18/19/20
Recall some useful supportive therapies for AML
Recall some sites of leukaemic involvement in ALL that you wouldnt see in AML
Thymus, testes, CNS
Which type of leukaemia is most likely to present with long bone pain?
ALL
