leukaemia and lyphoma Flashcards
which cells are myeloid lineage and which are lymphoid lineage
lymphoid - B, T and NK cells
myeloid - the rest
difference between leukemia and lymphoma
leukaemia - spills into peripheral blood from bone marrow
lymphoma - more discreet in tissues, hardly any involvement of blood
what are the 5 types of lymphocytic malignancies
acute lymphocytic leukemia
chronic lymphocytic leukemia
hodgkin’s lymphoma
non-hodgkin’s lymphoma
plasma cell dyscrasias
what are the 3 types of myeloid malignancies
acute myeloid leukemia
myelodysplasic syndromes
myeloproliferative conditions
classic presentation of acute leukemia
bone pain
pancytopenia (fatigue, infection, fever, bleeding, bruising)
which blood cell malignancy is the most common in children
ALL
cure rate of ALL
80% in children
which blood cell malignancy is the most common leukemia in the western world in adults
CLL
what is the most common presentation of CLL
lymphadenopathy
how can CLL be cured
allogenic transplant
what is typical for CLL on a histological slide
Smudge cells
what is the difference between Hodgkins and non-Hodgkins lymphoma in respect to where it is
Hodgkins = typically localised to a single axial group
non-H = usually involves multiple nodes, including peripheral nodes
what what is the difference between Hodgkins and non-Hodgkins lymphoma in respect to spread
Hodgkins = orderly pattern of contiguous spread from one group of nodes to the next
Non-H = non-contiguous pattern of spread
what is the difference between Hodgkins and non-Hodgkins lymphoma in respect to mesenteric nodes and Waldeyers ring
Hodgkins = rarely involves it
Non-Hodgkins = often involved
what is typical for hodgkins lymphoma on histological slide
Reed-Sternberg cells (large cells, multinucleated with multiple nuclear lobes)
what is typical for AML on histological slide
blasts with Auer rods
what causes CML
philadelphia chromosome t(9;22)
treatment of CML
imatinib = inhibitor of the tyrosine kinase receptor
3 structural components of a Lymph node
stroma
lymphatic sinuses
vascular
where are the B and T cells located in a lymph node
cortex = B cells
paracortex = T cells
what is in the medulla of a lymph node
network of lymphatic sinuses, drain into efferent lymphatics
what is the pathogenesis of leukaemia
somatic mutatinos in a multipotential primitive cell/more differentiated progenitor cell resulting in a gene which encodes for a protein that disrupts normal cell pathway (and therefore predisposes to malignant transformation)
what is the difference between acute and chronic leukaemia
acute = proliferation/accumulation of blasts
chronic = accumulation of maturer white cells
which out of Acute or chronic leukaemia is more serious
acute - rapid clinical course and fatal if untreated
what are the types of chronic leukaemia
chronic lymphocytic leukaemia
chronic myeloid leukaemia
hairy cell leukaemia
chronic myelomonocytic leukaemia
common symptoms of leukaemia
weight loss, fever, frequent infections
easy SOB
weakness
bone pain or tenderness
fatigue, loss of appetidie
lymphadenopathy
hepatosplenomegaly, splenomegaly
night sweats, easy bleeding/brusing, purplish spots
which CD markers are typical for CLL
CD19 and CD5
what do you see on a histological slide in someone who has CML
leukocytosis
with a left shift
what is typical for ALL on histological slide
blasts - with no Auer rods or granules
what is the common translocation that causes AML
t(15:17)
how does imatinib work
- inhibits BCR-ABL autophosphorylation and phosphorylation
- induces apoptosis
- inhibits proliferation
what is ABT-199
selective Bcl-2 inhibitor for treatment of CLL
what enters/exits the lymph node at the hilum
enters = artery
exits = vein and lymphatics
where does the lymphatic vessels enter the lymph node
around the outside of the node through the capsule through afferent lymphatic
what is the histological “sign” of an active lymph node
germinal centres in the cortex
what things are found in the paracortex of the lymph node
naive T cells
high endothelial venules
interdigitating dendritic cells
what is a primary follicle of the lymph node
follicle of B cells that are unactivated
what things are found in primary follicles
naive B cells
follicular dendritic cells
t cells
what things are found in the mantle zone
Naive B cells
where is the mantle zone
directly around the germinal centres
how do the T cells come into the lymph node
via endothelial venules
what are the “markers” for immunohistochemistry for B and T cells
B = CD20
T = CD3
what is the differentiation steps between a naive B cell and a plasma cell
centroblasts –> centrocytes –> immunoblasts –> plasma cells
where does maturation of the B cells occur
naive B cell –> immunoblasts in germinal centre
final maturation into plasma cells in medullary cords
what are the 2 major causes of lymphadenopathy
reactive inflammatory and infective
neoplastic
when do you see acute non-specific lymphadenitis
nodes draining directly from a microbial infection
what are the histological signs of acute non-specific lymphadenitis
neutrophil infiltration, oedema, follicular hyperplasia
what is the difference in the presentation between acute and chronic non-specific lymphadenitis
acute = nodes large and painful
chronic = generally non tender
what are the 5 broad causes of non-specific lymphadenitis
follicular hyperplasia (humoral response)
paracortical (cellular response)
sinus histiocytosis (non-specific)
granulomatous inflammation
mixed
what are the causes of neoplastic lymphadenopathy
primary tumour: Hodgkins or non-Hodgkins
secondary tumours (metastases)
leukaemic infiltration
what are the histological signs of Hodgin lymphoma
Reed Sternberg cells
neoplastic germinal centre B cells
risk factors for lymphoma
- immunosuppresion or ID
- some autoimmune diseases
- EBC, H pylori
- environmental
what causes Burkitt’s lymphoma
translocation (3:8) –> overproduction of MYC oncogene
what are the B symptoms of lymphoma
temperature >38
night sweats
weight loss >10% from baseline in 6 months
what do Reed-Sternberg cells look like
large cell with abundnant cytoplasm and a large bilobate nucleus with prominent eosinophilic nucleoli
is B or T cell non-hodgkins lymphoma more common
B
which leukaemia is associated with philadelphia chromsome
CML
What is the important GF for the early progenitor haematopoietic cells
c-Kit
how is the cell cycle told to start
activation via cytokine Receptor –> activates intracellular signalling –> transcription factor activation –> activates Cyclin D –> activates CDK4 –> activates G1
what are the 6 hallmarks of cancer
- autonomous growth signalling
- evading growth inhibitory signals
- evasion of apoptosis
- activating invasion and metastasis
- angiogenesis
- immortality
which leukaemias/lymphomas are due to autonomous growth signalling
CML
ALL
Burkitt’s lymphoma
Which leukaemias/lymphomas are due to an evasion of apoptosis
CLL
Which leukaemia/lymphoma is due to evasion of growth inhibitory signals
burkitt’s lymphoma
what are the 4 emerging hallmarks of cancer
- deregulating cellular energetics
- avoiding immune destruction
- tumour promoting inflammation
- genome instability and mutation
what makes lymphoid cells sensitive to mutations
- prone to mutations during antibody diversification with the enzyme AID
- infection with EBC or H pylori leads to long term survival of cells –> secondary chronic inflammation = cancer
What is the difference between myelodysplastic syndromes and myeloproliferative disorders
MD = cytopenia from disorderly proliferation in BM and a lack of mature cells in blood
MP = increased production in 1 or 2 categories of mature cells
mean survival of CML without treatment
3 years
what kind of cells do you get during a blast crisis of CML
myeloid origin or pre-B origin
What is the translocation of the philadelphia chromosome
9:22
(Bcr-Abl)
Abl = chromosome 9
Bcr = chromosome 22
affect of Bcr-abl translocation
causes mostly increased proliferatin and survival of haematopoietic cells
action of gleevac
specific inhibitor of BCR-ABL
why is it not possible to cure someone of CML from Gleevec
the progenitor cells that give rise to the proliferating CFUs do not cycle often and therefore the treatment cannot target them
what causes the blast crisis in CML
further mutations in the cells with philadelphia chromosome leading to:
which cells area affected in CLL
naive B cell or memory B cell in germinal centre
what is the cause of CLL
loss of regulatory miRNA 15a and 16-1 that lead to high levels of Bcl-2, leading to failure of cells to apoptose
Which specific further mutations can lead to a worser outcome for a patient with CLL
ZAP-70 and p53
what is the lymphoma that is pretty much the same as CLL
SLL (small lymphocytic lymphoma)
what do you see in the lymph node with CLL
- loss of normal lymph node architecture due to infiltration of small round lymphocytes
which mutations (initial and subsequent) act at which different places of the cell cycle for CLL
elevated Bcl-2 = prevents apoptosis induced by p53
elevated ZAP-70 = causes autonomous signalling (no longer need receptor activation)
loss of p53 = prevents DNA repair, apoptosis and inhibition of the cell cycle by p16
explain the new up and coming treatment for CLL
ABT-199 = BH3 only drug that inhibitors Bcl-2
how does elevated Bcl-2 cause reduced apoptosis
causes a closed channel in the mitochondrial membrane preventing the escape of cytochrome c (therefore cannot activate executioner caspases needed for apoptosis)
functions of p53
- cell cycle arrest (to be able to repair mutations)
- activates repair processes
- directs a cell to apoptose if unable to fix mutation
