Haematological Malignancies Flashcards
What is meant by the two-hit model of leukamogenesis?
- Loss of function of transcription factors needed for differentiation of cells
- Gain of function mutations of tyrosine kinases to enhance proliferation
This leads to acute leukaemia development
What are the clinical features of leukaemia?
The symptoms are related to the bone marrow failure:
• Anaemai – fatigue, shortness of breath
• Low platelets (thrombocytopaenia) – bleeding
• Neutropenia – bacterial and fungal infections
• Bone pain
How does the cellular biology differ between acute and chronic leukaemia?
Acute leukaemia involves the accumulation of blast cells and there is a lack of differentiation with high growth, however, in chronic leukaemia there is an accumulation of mature cells with a failure of apoptosis
What is APML?
Acute promyelocytic leukaemia
Describe the pathogenesis of acute pro-myelocytic leukaemia (APML)
Involves the translocation of chromosomes 15 and 17 which leads to the production of a PML-RAR fusion protein. The result of this protein is that it binds to DNA and blocks transcription, ad therefore prevents the differentiation of promyelocytes. These cells therefore accumulate which leads to leukaemia and bone marrow failure.
How is PML-RARa fusion protein involved in the pathogenesis of acute pro-myelocytic leukaemia?
This fusion protein is formed (due to translocation between chromosome 15 and 17) which binds to DNA to block transcription and therefore prevents the differentiation of promyelocytes so these cells accumulate
Outline the treatment of acute promyelocytic leukaemia
All trans-retinoic acid binds to PML-RAR fusion protein in order to prevent the DNA binding and therefore the promyeloblasts are allowed to differentiate and can subsequently die from apoptosis.
How can you tell from nomenclature whether the monoclonal antibody is fully humanised or chimeric (half murine and half human)?
Chimeric (half murine, half human = imab
Fully humanised = umab
