Cancer 14: Leukemia Flashcards
What is leukemia?
–> results from mutations in a single lymphoid or myeloid stem cell
- -> mutations lead the progeny of that cell to show abnormalities in proliferation/ differentiation or cell survival
- -> leading to steady expansion of the leukaemic clone (deriving from that one mutant cell)
–> leukaemic cells replace normal bone marrow cells + circulating freely in the blood stream
What are the cells that can be involved in leukemia?
- pluripotent hematopoietic stem cell
- myeloid stem cell
- lymphoid stem cell
- pre B lymphocyte
- pro T lymphocyte
leukemia = described as either
a) chronic or acute
b) Lymphoid or Myeloid
what do these terms mean?
a)
chronic = Leukaemias that behave in a relatively ‘benign’ manner
acute = Leukaemias that behave in a ‘malignant’ manner
–> aggressive
b) Depending on the cell of origin, it can also be lymphoid or myeloid
how is leukemia classified?
Acute lymphoblastic leukaemia (ALL)
Acute myeloid leukaemia (AML)
Chronic lymphocytic leukaemia (CLL)
Chronic myeloid leukaemia (CML)
lymphoblastic - acute - immature
ymphocytic - resembles - mature lymphocytes
The important leukaemogenic mutations that have been recognized include:
- Mutation of proto-oncogene
- Creation of a novel gene
e. g. a chimaeric or fusion gene - Dysregulation of a gene when translocation brings it under the influence of the promoter or enhancer of another gene
- Loss of function of a tumour-suppressor gene –> contribute to leukaemogenesis (due to deletion or mutation of the gene)
- tendency to increased chromosomal breaks, the likelihood of leukaemia is increased
- if cell cannot repair DNA normally
- -> error persist
- Inherited or other constitutional abnormalities
- -> contribute to leukaemogenesis
- > e.g chr 21 –> down syndrome
What are some environmental causes of leukaemogenic mutations?
- Irradiation
- Anti-cancer drugs
- Cigarette smoking
- Chemicals—benzene
Leukaemia, like cancer in general, can be seen as an acquired genetic disease, resulting from somatic / germ cell mutation
Leukaemia, like cancer in general, can be seen as an acquired genetic disease, resulting from somatic cell mutation
What is the difference between acute and chronic myeloid leukaemia?
AML
- -> Mutation occurs
- -> loss of ability to mature
- -> so there is build up of immature cells/ myeloblasts/ blast cells’—in the bone marrow –> which spreads into the blood
failure of production of normal functioning end cells such as neutrophils, monocytes, erythrocytes, platelets
–> failure of immature cells to develop into mature T / B cells
CML
- -> mutations affects transcription factors
- -> affects gene encoding protein in signalling pathway between cell surface receptor + nucleus
- -> protein encoded = memb receptors or cytoplasmic protein
- ->reduced apoptosis
- -> leukemia clone expands progressively \
–> leukemia cells T/ B cells are mature although abnormal
NOTE:
AML = failure of production of end cells CML = increased production of end cells
How does leukaemia cause the disease characteristics?
a) accumulation of abnormal cells –> lead to
- Leucocytosis
- bone pain (if leukaemia is acute),
- hepatomegaly,
- splenomegaly lymphadenopathy (if lymphoid),
- thymic enlargement (if T lymphoid),
- skin infiltration
b) Metabolic effects of leukaemic cell proliferation—> leads to
- hyperuricaemia + renal failure,
- weight loss,
- low grade fever,
- sweating
c) Loss of normal immune function –> due to loss of T/B cell function (CML)
Acute Lymphoblastic Leukaema = a disease of children / adult
AML = a disease of children
Epidemiology suggests that B-lineage Acute Lymphoblastic Leukaemia may result from =
- delayed exposure to a common pathogen
- -> BUT early exposure to pathogens protects
i.e if you grew up in a place with increased exposure to infections etc. –> you are SAFER
if you grew up elsewhere but you move somewhere else later –> YOU ARE AT RISK
Epidemiology also suggests that some leukaemias in infants and young children result from:
- Irradiation in utero
- In utero exposure to certain chemicals (e.g Baygon, Dipyrone )
- Epstein–Barr virus infection
-
Acute lymphoblastic leukaemia—clinical features include:
a) Resulting from accumulation of abnormal cells
- -> Bone pain
- -> Hepatomegaly
- -> Splenomegaly
- -> Lymphadenopathy
- -> Thymic enlargement
- -> Testicular enlargement
b) Resulting from crowding out of normal cells
- -> Fatigue, lethargy, pallor, breathlessness (caused by anaemia)
- -> Fever + other features of infection (due to neutropenia)
- -> Bruising, petechiae, bleeding (caused by thrombocytopenia)
What re the hematological features of Acute lymphoblastic leukemia?
- Leucocytosis with lymphoblasts in the blood
- Anaemia (normocytic, normochromic)
- Neutropenia
- Thrombocytopenia
- Lymphoblasts replace normal bone marrow cells
What are some methods of investigating acute lymphoblastic leukemia?
- Blood count and film
- Check liver and renal function and uric acid
- Bone marrow aspirate
- Cytogenetic/molecular analysis
- -> gives us info about prognosis
- -> ALL = has multiple cytogenetic subsets with diff prognosis –> so may require different treatment
- -> hyperdiploidy = good prognosis
- Chest X-ray
- immunophenotyping
- -> to distinguish AML from ALL
