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Haematology > Haem: Acute Leukaemia > Flashcards

Haem: Acute Leukaemia Flashcards

1
Q

Explain the cell lineage of pluripotent haematopoietic stem cells

A

pluripotent haematopoietic stem cells can give rise to lymphoid or myeloid stem cells.

Myeloid cells differentiate into megakaryocytes-erythrocytes cells OR granulocytes-monocyte cells.

Lymphoid cells differentiate into B or T cells

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2
Q

Which cells does AML manifest with?

A

Any of the cells of myeloid lineage

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3
Q

Which cells does CML manifest with?

A

Chronic phase - Myeloid cells
Acute phase - Lymphoblastic crisis (Particularly B cells)

CML occurs in a pluripotent haematopoietic stem cell

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4
Q

What do blast cells typically look like?

A

High nucleus : cytoplasm

Diffuse chromosome pattern

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5
Q

What type of chromosome abnormalities are seen in AML?

A

Duplication (trisomy) - Cr 8 and 21 (As seen in Down’s syndrome too)

Loss - Possibly of Tumour suppressor genes or Cr repair systems

Translocation

Deletion of part of a chromosome

Point mutations - NPM1 (Good prognosis) and CEBPA (Good prognosis if both copies are mutated)

Partial duplication (FLT3 which is a bad prognosis)

Cryptic deletion

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6
Q

What type of chromosome abnormalities are seen in ALL?

A

Translocation leading to abnormal regulation of genes and creation of new fusion genes

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7
Q

What are the normal granulocyte maturation stages?

A

Myeloblast 🡪 promyelocyte 🡪 myelocyte 🡪 metamyelocyte 🡪 band form 🡪 neutrophil

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8
Q

How does the normal granulocyte maturation process differ in AML?

A

Differentiation of the cells is disrupted, leading to accumulation of blast (immature) cells

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9
Q

What is necessary for Leukaemogenesis in AML

A

Multiple genetic hits

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10
Q

What are type 1 abnormalities

A

Mutation promotes proliferation and survival (anti-apoptosis)

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11
Q

What are type 2 abnormalities

A 
Block differentiation (which would normally be followed by apoptosis)
This leads to an accumulation of blast cells
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12
Q

Explain how leukaemogenesis can happen in2 ways in Core Binding factor (CBF)?

A

Translocation of 8:21 leads to partial block in differentiation (mixture of mature and blast cells)

Inversion of Cr 16 leads to arrest in differentiation leading to some cells to mature into bizarre eosinophil precursors

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13
Q

How many blast cells is needed to call the malignancy acute leukaemia?

A

20% of the blast cells

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14
Q

What is the dominant negative effect?

A

when a single abnormal chromosome dominates over the normal one

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15
Q

What is APML?

A

It is characterised by an excess of abnormal promyelocytes

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16
Q

How does APML present?

A

DIC and hyperactive fibrinolysis - Haemorrhage, low platelet

Acute presentation and is a medical emergency

17
Q

What causes APML?

A

Translocation between Cr 15 and 17 forming the PML-RARA fusion gene

18
Q

What can you see on a blood film with APML?

A

Auer rods - Promyelocytes

19
Q

What can you see on the blood film of of the APML variant?

A

Bilobed nuclei

20
Q

What are the type 1 and 2 mutations in APML?

A

Type 1 mutation: FLT3-ITD – this makes the prognosis worse

Type 2 mutation: PML-RARA

21
Q

What are the type 1 and 2 mutations in CBF leukaemias?

A

Type 1 mutation: sometimes mutated KIT

Type 2 mutation: mutation affecting function of CBF

22
Q

How is APML treated?

A

By targeting the molecular mechanism, you unblock the blocked differentiation and the leukaemic clone matures into end cells which then die

23
Q

How to differentiate between AML and ALL?

A 
Auer rods - Myeloid 
Granulocytes - Myeloid 
Myeloperoxidase stain - Myeloid
Sudan Black - Myeloid 
Non-specific esterase stain - Myeloid

Absence of all if this means ALL lol

24
Q

What does the presence of TdT and/or CD34 indicate?

A

Primitive cell (non lineage specific)

25
Q

What are the clinical features of bone marrow failure in AML?

A

Anaemia
Neutropaenia - Infections, necrotising fascitis, sepsis
Thrombocytopaenia- bruising, bleeding
DIC - Pinpoint petachiae or echymosis or peripheral vessel obstruction or gangreen

26
Q

What are the clinical features of local infiltration in AML?

A

Splenomegaly

Hepatomegaly

Gum infiltration (if it is a monocytic lineage)

Lymphadenopathy (only occasionally)

Skin, CNS or other sites

Can cause cranial nerve palsies

This can occur as a result of meningeal infiltration

Hyperviscosity if WBC is very high
This can cause retinal haemorrhages or retinal exudates

27
Q

How is AML diagnosed?

A

Blood film - Circulating blasts, auer rods, presence of granules

Immunophenotyping

Aleukaemic leukaemia

28
Q

What is Aleukaemic leukaemia

A

This is when there are NO leukaemic cells in the peripheral blood but the bone marrow has been replaced

29
Q

How is AML treated?

A 
RBCs
Platelets
FFP/ cryoprecipitate if DIC
Antibiotics
Long line inserted into a central vein
Allopurinol (to prevent uric acid production to prevent AKI)
Fluid and electrolyte balance
Chemotherapy
Targeted molecular therapy
Transplantation
30
Q

What are targets of chemo treatment?

A

Damage the DNA of the leukaemic cells

Leave the normal stem cells unaffected

31
Q

How to treat Philadelphia Cr positive cases?

A

Tyrosine kinase inhibitors

32
Q

How common is ALL in kids and do they tend to be Philadelphia Cr positive in kids?

A

MOST COMMON childhood malignancy

chances of it being Philadelphia Cr positive increases with age

33
Q

What are the clinical features of ALL?

A 
Bone marrow failure
Anaemia
Neutropaenia
Thrombocytopaenia
Local infiltration
Lymphadenopathy (+/- thymic enlargement)
Splenomegaly
Hepatomegaly
Testes, CNS, kidneys or other sites
Bone (causing pain)
34
Q

What would you find in a blood film in ALL?

A

Anaemia
Neutropaenia
Thrombocytopaenia
Usually lymphoblasts - Only supposed to be found in the bone marrow

35
Q

What genetic picture is good prognosis in ALL?

A

Hyperdiploidy
t(12;21)
t(1;19)

t(9;22)- this is the Philadelphia chromosome

36
Q

What genetic picture is poor prognosis in ALL?

A

t(4;11)

Hypodiploidy

37
Q

In general what are the symptoms of ALL in kids?

A

bone pain, limping, pallor, bruising, organomegaly

Haematology (10 decks)

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