Haem: Acute Leukaemia Flashcards
Explain the cell lineage of pluripotent haematopoietic stem cells
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
Which cells does AML manifest with?
Any of the cells of myeloid lineage
Which cells does CML manifest with?
Chronic phase - Myeloid cells
Acute phase - Lymphoblastic crisis (Particularly B cells)
CML occurs in a pluripotent haematopoietic stem cell
What do blast cells typically look like?
High nucleus : cytoplasm
Diffuse chromosome pattern
What type of chromosome abnormalities are seen in AML?
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
What type of chromosome abnormalities are seen in ALL?
Translocation leading to abnormal regulation of genes and creation of new fusion genes
What are the normal granulocyte maturation stages?
Myeloblast 🡪 promyelocyte 🡪 myelocyte 🡪 metamyelocyte 🡪 band form 🡪 neutrophil
How does the normal granulocyte maturation process differ in AML?
Differentiation of the cells is disrupted, leading to accumulation of blast (immature) cells
What is necessary for Leukaemogenesis in AML
Multiple genetic hits
What are type 1 abnormalities
Mutation promotes proliferation and survival (anti-apoptosis)
What are type 2 abnormalities
Block differentiation (which would normally be followed by apoptosis) This leads to an accumulation of blast cells
Explain how leukaemogenesis can happen in2 ways in Core Binding factor (CBF)?
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
How many blast cells is needed to call the malignancy acute leukaemia?
20% of the blast cells
What is the dominant negative effect?
when a single abnormal chromosome dominates over the normal one
What is APML?
It is characterised by an excess of abnormal promyelocytes
How does APML present?
DIC and hyperactive fibrinolysis - Haemorrhage, low platelet
Acute presentation and is a medical emergency
What causes APML?
Translocation between Cr 15 and 17 forming the PML-RARA fusion gene
What can you see on a blood film with APML?
Auer rods - Promyelocytes
What can you see on the blood film of of the APML variant?
Bilobed nuclei
What are the type 1 and 2 mutations in APML?
Type 1 mutation: FLT3-ITD – this makes the prognosis worse
Type 2 mutation: PML-RARA
What are the type 1 and 2 mutations in CBF leukaemias?
Type 1 mutation: sometimes mutated KIT
Type 2 mutation: mutation affecting function of CBF
How is APML treated?
By targeting the molecular mechanism, you unblock the blocked differentiation and the leukaemic clone matures into end cells which then die
How to differentiate between AML and ALL?
Auer rods - Myeloid Granulocytes - Myeloid Myeloperoxidase stain - Myeloid Sudan Black - Myeloid Non-specific esterase stain - Myeloid
Absence of all if this means ALL lol
What does the presence of TdT and/or CD34 indicate?
Primitive cell (non lineage specific)
