65542
Haematopoietic System Malignancies 2
- Lymphomas
- Malignancy of lymph nodes
- Hodgkins Lymphoma
- Non-Hodgkin's Lymphoma
- Diffuse large B cell lymphoma
- Follicular lymphoma
- Lots of others
- Diffuse large B cell lymphoma
- Malignancy of lymph nodes
- Hodgkin's Disease
- Often seen in young adults
- Epstein-Barr virus is often integrated in malignant cells
- Reed-Sternberg cells are malignant cells -
surrounded by a sea of normal immune cells
- Curable with chemotherapy/radiotherapy in most cases
- Often seen in young adults
- Non-Hodgkin's Lymphoma
- Mantle cell lymphoma
- Small lymphocytic lymphoma
- Follicular lymphoma
- Indolent (slow growing) but curable
- 10 year median survival
- Patients present with lymphadenopathy
- t(14;18) present in 90% of cases
- Increases expression of BCL2 (anti-apoptosis protein)
- Translocation puts BCL2 near immnoglobulin heavy chain gene
- Translocation puts BCL2 near immnoglobulin heavy chain gene
- BCL2 inhibitors in clinical trials
- Increases expression of BCL2 (anti-apoptosis protein)
- Diffuse large B cell lymphoma
- Most common
- Lymph node replaced by large sheets of lymphoma cells
- Large cells in diffuse sheets
- Large cells in diffuse sheets
- Potentially curable
- Monoclonal antibody therapy
- Cells express CD20
- Rituximab (antibody against CD20) kills lymphoma cells
- Signal for apoptosis via complement cascade and MAC
- Cells engulfed by macrophages
- Cells engulfed by macrophages
- Signal for apoptosis via complement cascade and MAC
- Cells express CD20
- Monoclonal antibody therapy
- Aggressive
- Most common
- Mantle cell lymphoma
- Epigenetic Regulation of Gene Expression
- EZH2 methylates K27, inhibiting transcription
- Gain of function in 27% follicular lymphoma
- Both mutations reduce transcription
- Gain of function in 27% follicular lymphoma
- MLL2 methylates K4, increasing transcription
- Loss of function of MLL2 in 90% follicular lymphomas
- Loss of function of MLL2 in 90% follicular lymphomas
- EZH2 methylates K27, inhibiting transcription
- Chronic Lymphocytic Leukaemia (CLL)
- Lymphoma of the blood/bone marrow
- Caused by chronic proliferation of mature B cells
- Usually presents with abnormal blood tests (discovered in routine test)
- Very high white blood cells count - 200 (normal is 10)
- Very high white blood cells count - 200 (normal is 10)
- Can present with lymphadenopathy
- B cell activation
- Antigen binds
- Lyn kinase phosphorylates Syk kinase
- Activates Bruton tyrosine kinase
- Phosphorylates Plcg
- Activates DAG and IP3
- Increases Ca2+
- Proliferation and survival via Nf-kappaB
- Proliferation and survival via Nf-kappaB
- Increases Ca2+
- Activates DAG and IP3
- Phosphorylates Plcg
- Activates Bruton tyrosine kinase
- Lyn kinase phosphorylates Syk kinase
- Lyn kinase, Syk kinase and Bruton
tyrosine kinase all increased in CLL
- Bruton tyrosine kinase inhibitors are in late stage clinical trials - have efficacy
- Bruton tyrosine kinase inhibitors are in late stage clinical trials - have efficacy
- Antigen binds
- Lymphoma of the blood/bone marrow
- Myeloma
- Common
- Plasma cells have become malignant
- Produce an antibody which forms a
monoclonal band in serum electrophoresis
- Not present in normal patients
- Not present in normal patients
- Attacks bone, spinal cord, kidneys and causes bone marrow failure
- Kidney tubules are blocked up by protein containing antibody light chains
- Causes swelling of the tongue
- Kidney tubules are blocked up by protein containing antibody light chains
- Treatable but not curable
- Chemotherapy and radiotherapy used
- New agents - thalidomide and proteasome
inhibitors (target protein degredation)
- Chemotherapy and radiotherapy used
- Common
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