Leukemia (19.02.2020) Flashcards
1
Q
What is leukemia?
A
- Cancer of the blood
- literally “white blood”
- name was given because the first cases of leukaemia recognized had a marked increase in the white cell count which made the blood look whiter
- bone marrow disease and not all patients have abnormal cells in the blood
2
Q
Leukemia statistics
A
- 5% of all cancers are cancers of the blood
- In the UK approximately 60 people every day are diagnosed with a cancer of the blood
- Blood cancers are the most common cancers in men and women aged 15‒24
- They are the main cause of cancer death in people aged 1‒34 years
- One in 45 of the UK population will die of leukaemia, lymphoma or myeloma
3
Q
What causes this cancerous white cell expansion?
A
- results from a series of mutations in a single lymphoid or myeloid stem cell
- These mutations lead the progeny of that cell to show abnormalities in proliferation, differentiation or cell survival leading to steady expansion of the leukaemic clone
- new mutation in a single cell giving it a growth or survival advantage
- emergence of a leukaemia clone
4
Q
Which cells can be involved in leukemia?
A
pluripotent heamatopoietic stem cell
- myeloid stem cell (gives rise to myeloid leukemias)
- lymphoid stem cell
- Pre-B lymphocye
- Pre-T lymphocyte
- NK
- leukemias and lymphomas
5
Q
What is different about leukaemia?
A
- different from other cancers
- Most cancers exist as a solid tumour
- However, it is uncommon for patients with leukaemia to have tumours
- More often they have leukaemic cells replacing normal bone marrow cells and circulating freely in the blood stream
- Dif because haemopoietic and lymphoid cells behave differently from other body cells
- Normal haemopoietic stem cells can circulate in the blood and both the stem cells and the cells derived from them can enter tissues
- Normal lymphoid stem cells recirculate between tissues and blood
6
Q
Benign and malignant leukemias
A
- concepts of invasion and metastasis cannot be applied to cells that normally travel around the body and enter tissues
- other ways of distinguishing a ‘benign’ condition from a ‘malignant’ condition and haematologists usually use different words for these concepts
- relatively ‘benign’ manner: called chronic—that means the disease goes on for a long time
- behave in a ‘malignant’ manner : called acute—that means that, if not treated, the disease is very aggressive and the patient dies quite rapidly
7
Q
chronic and acute leukemias - what is the implication?
A
- chronic behave in a more ‘‘benign’’ manner
- acute behave more in a ‘‘malignant’’ manner
8
Q
How is leukaemia classified?
A
- It follows from what has been said that leukaemia can be acute or chronic
- Depending on the cell of origin, it can also be lymphoid or myeloid
- Lymphoid can be B or T lineage
- Myeloid can be any combination of granulocytic, monocytic, erythroid or megakaryocytic
9
Q
Leukemia types
A
Acute lymphoblastic leukaemia (ALL)
Acute myeloid leukaemia (AML)
Chronic lymphocytic leukaemia (CLL)
Chronic myeloid leukaemia (CML)
Note: lymphoblastic
lymphocytic
10
Q
Why do people get leukaemia?
A
- arises from a series of mutations in a single stem cell
- Some mutations result from identifiable (or unidentifiable) oncogenic influences
- Others are probably random errors—chance events—that occur throughout life and accumulate in individual cells
- acquired genetic disease, resulting from somatic mutation
- Mutation in germ cells may bring favourable, neutral or unfavourable characteristics to the species
- Somatic mutation may be beneficial*, neutral or harmful
- A rare occurrence but can lead to reversion to normal phenotype in some cells in individuals with an inherited abnormality, e.g. an immune deficiency or bone marrow failure syndrome
- Leukaemia may thus be, in part, the inevitable result of the ability of mankind to change through evolution
11
Q
What can cause leukemia?
A
- Irradiation
- Anti-cancer drugs
- Cigarette smoking
- Chemicals—benzene
12
Q
What is the difference between acute and chronic myeloid leukaemia?
A
In AML, cells continue to proliferate but they no longer mature so there is
- A build up of the most immature cells— myeloblasts or ‘blast cells’—in the bone marrow with spread into the blood
- A failure of production of normal functioning end cells such as neutrophils, monocytes, erythrocytes, platelets (for 2 reasons)
- AML: responsible mutations usually affect TFs so that the transcription of multiple genes is affected
- Often the product of an oncogene prevents the normal function of the protein encoded by its normal homologue
- Cell behaviour is profoundly disturbed
- CML: responsible mutations usually affect a gene encoding a protein in the signalling pathway between a cell surface receptor and the nucleus
- The protein encoded may be either a membrane receptor or a cytoplasmic protein
- cell kinetics and function are not as seriously affected as in AML
- cell independent of external signals, alterations in the interaction with stroma and reduced apoptosis -> cells survive longer and the leukaemic clone expands progressively
13
Q
2 meanings of myeloid
A
- generic term for all myeloid cells
- can also refer to granulocytes
14
Q
What is the difference between acute and chronic lymphoid leukaemias?
A
- Acute lymphoblastic leukaemia has an increase in very immature cells— lymphoblasts—with a failure of these to develop into mature T and B cells
- In chronic lymphoid leukaemias, the leukaemic cells are mature, although abnormal, T cells or B cells
15
Q
How does leukaemia cause the disease characteristics?
A
Accumulation of abnormal cells leading to:
- Leucocytosis
- bone pain (if leukaemia is acute)
- hepatomegaly, splenomegaly lymphadenopathy (if lymphoid)
- thymic enlargement (if T lymphoid)
- skin infiltration
Metabolic effects of leukaemic cell proliferation—
- hyperuricaemia and renal failure
- weight loss
- low grade fever (die to higher metabolic rate)
- sweating (higher metabolic rate)
Crowding out of normal cells leading to
- anaemia
- neutropenia
- thrombocytopenia (bruising, can cause haemorrhages, swelling and hameorhage of the gums)
Loss of normal immune function as a result of loss of normal T cell and B cell function—a feature of chronic lymphoid leukaemia
16
Q
leukemia cutis
A
- infiltration of neoplastic leukocytes or their precursors into the epidermis, the dermis, or the subcutis, resulting in clinically identifiable cutaneous lesions.
- may follow, precede or occur concomitantly with the diagnosis of systemic leukemia
