Malignant Haematology Flashcards
What two categories are white blood cells broken down into?
Split into myeloid cells and lymphoid cells
Name some myeloid cells and are these granulocytes?
Neutrophils, eosinophils, basophils are all granulocytes
Monocytes are tissue macrophages and are not granulocytes
Name some lymphoid cells?
Natural killer cells
B lymphocytes
T lymphocytes
How many lobes do neutrophils normally have and are they common in adult blood?
Majority of mature myeloid cells in the body with three or 4 lobes.
How many lobes do hypersegmented neutrophils have?
Hypersegmented neutrophils are neutrophils with 5+ lobes.
Where are neutrophil precursors from?
Their precursors are normally only in bone marrow
What diseases are neutrophils important in?
Bacterial and fungal infections
What do chemotaxins do to neutrophils?
They direct them to the site of infection
What are some examples of chemotaxins?
Complements, leucocyte adhesion molecules
Neutrophils - What is phagocytosis?
The ability for neutrophils to ingest invading pathogens once they have been opsonized by complement.
How do neutrophils kill pathogens after creating the phagosome?
Reactive oxygen species and hydrolytic enzymes
What can neutrophils release that has antimicrobial properties?
Granules
What are NETS and what are they made of?
Neutrophil extracellular traps made of DNA
What does seeing myeloblasts make you concerned about and why?
These are really early neutrophil precursors and so you would worry about issues in the bone marrow not letting them form properly.
What do we mean by saying a blood film is left shifted?
You are seeing more immature cells
What do eosinophils have a special role in?
Allergic responses and parasitic defence
What do basophils contain?
Heparin (blood clotter) and histamine (inflammatory response)
What type of receptors do basophils have?
IgE
What do monocytes do?
Migrate to tissues and transforms into macrophages and dendritic cells
What do monocytes do during infection?
Phagocytose, antigen presentation and cytokine production
Where do monocytes reside?
Spleen
What is neutrophilia and what causes this?
Too many neutrophils and can be caused by pregnancy, inflammation, steroids, chemotherapy etc.
Benign Disorders - neutropenia - does this have ethnic variations?
Yes
Symptoms of neutropenia?
Recurrant infections, opportunistic and unusual infections
Can you get neutropenia where you have the correct number of neutrophils but they are non-functional?
Yes
lymphocytes - what part of the immune system are they in and what do they do?
innate immunity who identify known self antigens during antigen presentation
Where are lymphocytes produced?
Bone marrow
Where do t cells mature?
thymus
what are the secondary lymphoid organs lymphocytes circle round?
Lymph nodes and spleen
Do lymphocytes create memory cells?
yes
Plasma cells - what do these secrete?
Antibodies
What causes multiple myeloma?
Clonal proliferation of plasma cells
B lymphocytes - what receptors for antigen do they have?
Immunoglobin - IgM, IgG, IgA, IgE, IgD
What part of the B lymphocytes are variable for antigen specificity?
Fab region
Can B lymphocytes make memory B cells?
Yes
How do you identify a multiple myelonoma?
Detecting a monoclunal immunoglobulin fragment made by malignant plasma cells called a paraprotein
What can you find out about T cells from their receptor?
T-cell and you can work out if these all come from the one clone or several and adjuct reaction as needed.
What does the thymus do in T-lymphocytes?
Delete self reactive T cells
Select for T-cells with host HLA specificity
What are some types of markers T-cells express?
CD8 +ve cytotoxic cells
CD4 +ve helper cells
What do CD8 +ve cytotoxic cells do?
Bind to virus infected or damaged cells. They release cytotoxins to kill these cells by lysis or apoptosis?
What do CD4 +ve helper cells do?
Produce cytokines that activate macrophages B cells and NK cells
Do NK cells have receptors?
No but they express CD8
What part of the immune system is NK cells apart of?
Innate immune system
What types of cells do NK cells destroy through cytotoxic ways?
Viral infections and tumours
Immunodeficiency - what are some signs of this?
Clinically recurrant or unusual infections
Primary immunodeficiency can be what diseases?
These are inherited disorders such as X-linked agammaglobulinaemia, SCID or CVID
Secondary immunodeficiency diseases?
These are acquired disorders such as HIV, lymphoproliferative disorders, nephrotic syndrome, drug-induced lymphopenia
What would an acute disease refer to?
Overproliferation of immature cells
This happens more rapidly/ aggressive
What would chronic disease refer to?
Overproliferation of mature cells
There is a long history or indolent disease
Lymphoid disorders are about what?
Solid organs (lymphoma)
What are myeloid diseases concerning?
Blood/bone marrow (leukemia)
How would you investigate and classify haematological malignancies?
- Morphology
- Immunophenotyping
- Cytogenetics.
In myeloid can you only have acute or chronic leukemia?
Yes
In lymphoid can you only have acute or chronic lymphoma?
No you can also have acute and chronic leukemia too
What are some differences between high Grade and Low grade lymphoid diseases?
High grade is quick overproliferation and needs treatment whereas low grade is slower over proliferation/ indolent disease and in some cases needs no treatment.
Morphological changes to blood film - leukaemic blasts?
Large cells which more nucleus compared to cytoplasm
Morphological changes to blood film - myeoblasts?
Tend to have more granules
Can you tell lymphoid vs myeloid from a blood film?
No
Immunophenotyping - what are some cell marker expressions?
CD45 - common leucocyte antigen
CD34, TdT - immature progenitors
Myeloid - CD13, CD33
B lineage - CD19, CD22, CD10, Ig
T lineage - CD7 and CD3
What can CD antigens on cell surface tell you?
The lineage of the cell and how mature the cells are
Genetics of haematological malignancies - what happens in stable cells?
There is a balance between proto-oncogenes and tumour supression genes leading to regulated proliferation and apoptosis
Genetics of Haematological malignancies - what happens in a malignant cell?
Chemicals, radiation, drugs, virus, translocations, deletion etc can cause the tumour supressor gene to turn off and the oncogene increases its signal - this causes excessive proliferation and failure to apoptose
What is cytogenetics?
Karyotyping cells in metaphase to look for translocations, deletions and monosomies
What type of molecular studies can you use to genetically investigate malignancies?
PCR and FISH
Why use genetics?
Helps diagnose disease
Helps understand prognosis and treatment choice
Helps monitor responses to treatment (tailor therapy, minimal residual disease)
What causes acute leukemia?
Overproliferation of immature blast cells
What are symptoms of acute leukemia?
Variable cytopenias, leucocytosis or leucopenia. This is dependant on the stage of the disease, as the malignant cells overproliferate in the bone marrow they push the leucocytes into the blood, however once the bone marrow is full of malignant cells they can no longer make leucocytes.
When would you diagnose acute leukaemia?
More than 20% blasts in the bone marrow or through genetic testing
Where could acute leukemia infiltrate to?
Skin, gums, lymph nodes, liver, spleen, CNS
Who is most likely to get acute myeloid leukaemia (AML)?
All ages although does increase with age
AML - does this develop from primary mechanism or treatment related?
Both
What is the prognosis of AML?
It is variable and dependant on age and cytogenic/molecular findings.
It is poor in adults over 60 but is improving and more than 50% of children and young adults
What is meylodysplasia?
Progressive bone marrow failure due to abnormalities in any or all of the myeloid cell lines.
What age group is more likely to get myeodysplasia?
Older age group
Can myelodysplasia turn into AML?
Yes
What can cause myelodysplasia?
Radiotherapy or chemotherapy
Chronic myeloid leukemia (CML) - what causes this?
Clonal proliferation of mature bone marrow stem cells caused by the philadelphia chromosome which is a BCR-ABL fusion gene encoding tyrosine kinase signalling molecules.
CML - what are the symptoms of this?
High WCC but asymptomatic before this
What are the clinical features of CML?
Cytopenias, splenomegaly, constiruitional symptoms
Treatment and prognosis of CML?
Targeted treatment with tyrosine kinase inhibitors - good prognosis
Acute lymphoblastic leukaemia (ALL) - what age group is this most common in?
Children but has a second rise after 40
What are the clinical features of ALL?
Cytopenias, infilatration of marrow or other organs, constitutional.
What is the prognosis of ALL and what is this dependant on?
Dependant on age, minimal residual disease, WCC
Prognosis is good 80 - 90% cure in children
Chronic lymphocytic leukaemia (CLL) - what are the signs of this?
B cell lymphocytosis in peripheral blood and small mature lymphocytes.
Cytopenias either from marrow infiltration or autoimmune
CLL - what are some symptoms of this?
Lymphadenopathy and splenomegaly but usually asymptomatic and picked up on routine blood tests
Also, increased frequency/severity of infections - low immunoglobin level common
What age gets CLL?
Normally older ages
What is the prognosis of CLL?
Its usually indolent but can change into high grade and therefore not good then.
How would you investigate CLL?
Flow cytometry
Genetics - chromosomal abnormalities, p53 deletions = treatment resistance
What is a lymphoma?
Accumulation of malignant lymohocytes in lymphoid tissues and can infiltrate non-lymphoid tissues.
What are symptoms of lymphoma?
Fever, weight loss, night sweats
What are haematological findings of a lymphoma?
Cytopenias with advanced marrow disease
Can you get low grade or high grade lymphomas involving the B cells or T cells?
Yes
What would see on a lymphoma blood film?
So many of the same cell - lymphocytes
