Cancer as a disease: Leukaemia Flashcards
What percentage of all cancers are cancers of the blood?
5%
In what age group are blood cancers the most common in men and women?
15 and 24
At what age range is blood cancer the main cause of cancer?
Between 1 and 34
What causes leukaemia?
Series of mutations in a single lymphoid or myeloid stem cell which lead the progeny of that cell to show abnormalities in proliferation, differentiation or cell survival leading to steady expansion of leukaemic clone
Why is leukaemia different to most cancers?
Most cancers exist as a solid tumour whereas leukaemia is a diffuse infiltrate- uncommon to have tumours in leukaemia, they have leukaemia cells replacing normal bone marrow stem cells circulating freely in the blood
Instead of invasion and metastasis what is used to describe clinical behaviour/natural history of leukaemia?
Acute leukaemia- one that, if untreated, has profound pathological effects and leads to death in a matter of days, weeks or months i.e. aggressive
Chronic leukaemia- impairment of function in normal tissues and although it will eventually lead to death it won’t occur for a number of years
How is leukaemia classified following on from acute or chronic?
It is classified depending on the cell of origin so it is either:
Lymphoid- T/B cell lineage or NK cells
Myeloid- any combination of granulocytic, monocytic, erythroid or megakaryocytic
What are the four different types of leukaemia?
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Chronic lymphocytic leukaemia
Chronic myeloid leukaemia
What is the difference between lymphoblastic and lymphocytic?
Lymphoblastic refers to primitive, immature blast cells
Lymphocytic refers to mature cells or lymphocytes
What important leukaemogenic mutations have been recognised?
Mutation in a known photo-oncogene
Creation of a novel gene - e.g. chimeric or fusion gene e.g BCR-ABL
Dysregulation of a gene when translocation brings int under the influence of the promotor or enhancer of another gene
Apart from leukaemogenic mutations, what else can leukaemogenesis occur as a result of?
Loss of TS function- can result from deletion or mutation of the gene
Increased chromosomal breaking
Loss of DNA repair
Inherited or other constitutional abnormalities can contribute to leukaemogenesis e.g. Down’s syndrome
What cause leukaemogenic mutations?
Irradiation
Anti-cancer drugs
Cigarette smoking
Chemicals- benzene
What is the pathogenesis of acute myeloid leukaemia?
The most primitive cell- the myeloblast continues to proliferate without maturing so there is a build up in bone marrow with leakage into the blood
What causes the clinical manifestations to present in acute myeloid leukaemia?
Lack of mature functioning cells such as neutrophils, monocytes, erythrocytes and platelets
In acute myeloid leukaemia what do the mutations usually affect?
Transcription factors so transcription of multiple genes is affected and the product of oncogenes prevents the normal function of proteins encoded by the normal homologues therefore cell behaviour is profoundly disturbbed
What do the mutations usually affect in chronic myeloid leukaemia?
A gene encoding a protein in the signalling pathway between a cell surface receptor and nucleus- may either be a membrane or cytoplasmic receptor
Cell becomes independent of external signals, there are alterations in the interactions with stroma and there is reduced apoptosis so that cells survive longer and the leukaemia clone expands progressively
What’s the difference between acute and chronic lymphoid leukaemia?
In acute lymphoblastic leukaemia, there is an increase in lymphoblasts (very immature cells) with a failure of these to develop into mature T and B cells
In chronic lymphoid leukemia, the leukaemic cells are mature but abnormal T cells or B cells
What does accumulation of abnormal cells in leukaemia lead to?
Accumulation of abnormal cells leads to leucocytosis, bone pain (if leukaemia is acute), hepatomegaly, splenomegaly, lymphadenopathy, thymic enlargement (if T lymphoid) and skin infiltration
What do the metabolic effects of leukaemia cell proliferation include?
Metabolic effects of leukaemia cell proliferation include hyperuricaemia and renal failure, weight loss, low grade fever and sweating
What does the crowding out of normal cells in leukaemia lead to?
Anaemia, neutropenia and thrombocytopenia
Give some examples of associated leukaemia characteristics
Hand of a patient with AML may show bruising and oedema
CT scan of patient with AML may show intraventricular haemorrhage
Leukaemia cells migrate into places where bacteria are found by chemotaxis for example in gums
Loss of normal immune function leads to opportunistic infections
What age group is commonly affected by ALL?
Children
What does epidemiological evidence suggest in terms of factors for leukaemia?
B lineage may result from delayed exposure to a common pathogen
It relates to family size, new towns, socio-economic class, early social interactions and variations between countries
Some leukaemias in infants and children result from irradiation in utero or in utero exposure to certain chemicals
What clinical features result from crowding out normal cells?
Fatigue, lethargy, pallor and breathlessness (caused by anaemia)
Fever and other features of infection (caused by neutropenia)
Brusing, petechiae and bleeding (caused by thrombocytopenia)
What haematological features are there of leukaemia?
Leucocytosis with lymphoblasts in the blood, anaemia, neutropenia, thrombocytopenia and replacement of normal bone marrow cells by lymphoblasts
What investigations are used to diagnose leukaemia?
Blood count and films Liver/renal function and uric acid levels Bone marrow biopsy Cytogenic/molecular analysis Chest x-ray
What is cytogenetic and molecular genetic analysis useful for?
Managing the individual patient as it gives information about prognosis
What can be used to detect all leukaemogenic mechanisms?
Fluorescent in-situ hybridisation
What are the three aspects to leukaemia treatment?
Supportive care with red cell, platelet and antibiotics
Systemic chemotherapy
Intrathecal chemotherapy
