Leukaemia And Lymphoma Flashcards
What cells are all blood cells derived from
Multipotential haemopoitetic stem cells
What 2 cells do mutlipotential haemopoietic stem cells differenitate into
Common myeloid progenitor
Common lymphoid progenitor
What cells does myeloid progenitor cells give
Granulocytes
Red blood cells
What cells do lymphoid progenitor cells give rise to
Natural killer cells
Lymphocytes; t and b
What does leukemia arise from
Haemopoitetic stemm cells
What happens to the bone marrow when normal haemopoeisis is impaired
The bone marrow produces abnromal blood cells which leads to bone marrow failure
What happens when the bone marrow fails
You become:
anaemic
Prone to bleeding and bruising
Suspectible to infection
What are the 4 types of leukemia
Acute myeloid leukemia
Acute lymphoid leukemia
Chronic myeloid leukemia
Chronic lymphoid leukemia
What is the difference between chronic and acute leukemia
Acute leukemia involve the transformation of immature haemopoetic cells
Chronic leukemia invlve the cells that done further differentiation i.e are more mature cells
In chronic leukemia what can the accumulaton of cells lead to
Splenomegaly
Hepatomegaly
Lymphadenopathy
What is lymphoma
Cancer of the lymphoid tissue
What are the 2 main categories of lymphoma
Non hodgkin
Hodgkin lymphoma
What is lymphoma characterised by
Proliferation and accumulation of mature lymphocytes in lymphoid tissue resulting in lymphadenopathy and or hepatosplenomegaly
What are the b symptoms in lymphoma
Night sweats Intense prutitus Unexplained fever Unintentional weight loss Fatigue and generalised weakness
What investigations should you carry out in suspected blood cancer
FBC
UE, lft, CRP and calcium
Coagulation profile (PT,APTT, fibrinogen)
Blood culture and screening for infection
Blood film
Peripheral blood immunophenotyping
Diagnoistic bone marrow aspirate and trephine biopsy
If you suspect lymphom what investigations should you carry out
LDH
Lymph node biopsy and history
CT imaging and PET scan
What is acute promyelocytic leukemia
A subset of acute myeloid leukaemia
For myleoid progenitor cells to give rise to granulocytes what does it need to differnitate to
Myeloblast
What do myeloblast cells differnitate into to give neutrophils
Promyelocyte Myelocyte Metamyelocyte Band cell Neutrophil
In acute prmyelocyte leukemia what happens to the differentiation
There is a block to promyelocyte so no further differentiation occurs and you seen no neutrophils on the blood film
What is the distinct molecular abnormality that underpins acute promyelocytic leukemia
Recipricol translocation between chromosome 15 and 17
When recipricol translocation occur which gene forms
PML-RARA on chromosome 15 and RARA-PML on chromosome 17
When PML-RARA gene is translated what protein does it form
PML-RARA protein
What is the role of PML-RARA protein
Block the promyelocyte differentiation
What is the treatment of acute promyelocytic leukemia
Vitamin a derivate i.e all trans retinoic acid given with arsenic trioxide (ATRA)
What are the other treatment for other types of acute myeloid leukemia
Chemotherapy
Monoclonal antibody
Allogenic stem cell transplantation
What is chronic myeloid leukemia due to
Recipricol translocation of chromsome 9 and 22 that foms BCR-ABL gene
What is the specific treatment of chronic myeloid leukemia
Tyrosine kinase inhibitor to stop the fusion of bcr and abl gene e.g imatinib
What is a problem of using imaitib
The patient can develop imatinib resistance
How do we solve imatinib resistance
Using 2 and 3rd generation tyrosine kinase inhibitors
What are the features of CML on a blood film
Few rbc and platelets
Many white blood cells
Eosinophil precursors
What is chronic lymphocytic leukemia characterised by
Accumulation of mature b lymphocytes
What is the pathobiology of chronic lymphocytic leukemia
B cell receptors drive CLL proliferation and CLL cells express BCL-2 (anti-apoptotic protein) which makes them resistant to apoptosis
What is the treatment of CLL
Chemotherapy Monoclononal antibodies e.g rituximab Chemoimmunotherapy BCR signalling inhibitors e.g ibrutinib BCL2 inhibitor e.g venetoclax
What are the symptoms of hodgkin lymphoma
B symptoms
Lymphadenopathy
Mediastinal lymph node mass
What is the treatment of Hodgkin’s lymphoma
Chemotherapy and radiotherapy
Monoclonal antibody e.g brentuximab
Immune checkpint PD1 inhibitor
Autologous stem cell transplatantion
What is a feature of hodgkins lymphoma and histology
Sternbers cell (owle eye cells)
In hodgkin lymphoma what is the role of PD1
- EBV Infection or JAK/STAT activation mediate the expression of PDL1 on the cell surface of reenberg cells
- PDL1 interacts with PD1 receptors on t cells which causes on inhibitory signal to prevent t cells from destroying it
What is the action of PD1 inhibitors in the treatment of hodgkin lymphoma
- PD1 inhibitors block the interaction of PDL1 on the reenberg cell
- This promotes t cell killing
What receptor does sternbeg cell express on the surface
Cd30
What is the mechanism of action of brenutixumab
Binds to CD30 and become internalised into the sternberg cell
The antibody i.e brunitixumab releases toxin to kill the cell
What is a common type of non-hodgkin lymphoma
Large b cell lymphoma
What does immunohistochemistry for b cell lymphoma show
Positive cd20
Negative cd3
Overepxressed bcl6
What is the treatment of large b cell lymphoma
Cd20 monoclonal antibodt e.g retuximab
CAR T cell therapy
What is CAR T cell therapy
You collect t cell from the patient
T cell is engineered with an artificial t cell receptor that recognise cd19 on lymphoma cells
CAR T cell exert cytotoxic activity by interacting with C19 and killing the lymphoma
