Leukemia Flashcards
leukemia definition
cancer of the body’s blood forming tissues
neoplasm
abnormal new growth
benign tumour
remain localised and do not metastasize
malignant tumour
metastasize through lymphatic channels or blood vessels to other lymph nodes and tissues on the body
carcinoma
90% of cancers - cancer of epithelial cells
sarcoma
rare - cancer of connective tissues
leukemias
8% of tumours - liquid tumours.
Originates from hematopoietic stem cells in bone marrow.
Originates from myeloid and lymphoid lineages
lymphomas
8% of tumours with leukaemias - liquid tumours.
lymphomas arise from cells of the immune system
2 types of cancer genes
proto-oncogenes and tumour surpressor genes
proto-oncogenes
over 100 known
proteins that promote cell cycle
mutations lead to oncogenes, promote cells growth regardless of circumstance
tumour suppressor genes
proteins that inhibit cell cycle
12 known
mutations lead to cell cycle not stopping when it should
what tumour suppressor gene plays a role in myeloid leukemia?
neurofibromatosis type 1
symptoms of leukaemia
weight loss
fever
frequent infections
shortness of breath
weakness of muscles
swelling of lymph nodes
prone to infections and bruising
what cells arise from lymphoid linage?
NK cells, B cells, T cells, lymphoid dendritic cell, plasma cell
how does leukaemia occur?
several mutations of hematopoietic stem cell (or cell formed later in linage) - forms leukaemia stem cell - forms blasts
all descendant cells in linage contain this mutation
general mechanisms of leukaemia transformed cell. (4)
impaired differentiation
increased cell survival
increased proliferation
increased self renewal
what is metastasis
spread of cancer
cause of leukaemia
genetic mutation/ oncogene activation
increased rate of proliferation
reduced apoptosis
accumulation of blasts in bone marrow
cause of mutations
hereditary
chromosomal abnormalities
chemical agents
viruses
3 chromosomal abnormalities in leukaemia
deletion of chromosome
inversion of chromosome (rearrangement or segment is reversed)
translocation (exchange of genetic material between chromosomes)
how many chromosomes are involved in a chromosomal inversion?
2
how many chromosomes are involved in a chromosomal translocation?
2
when in the linage do acute and chronic leukaemia form?
early mutations in the linage forms an acute leukaemia.
mutations later in linage forms a chronic leukaemia.
what type of leukaemia forms blasts?
acute only
what leukaemia is most common in children?
acute lymphoid leukaemia
why do infections and aneamias increase with leukaemia ?
leukaemia causes suppression of other marrow elements, therefore lack of normal rbcs, wbcs and platelets
acute leukaemia characteristic
uncontrolled proliferation of poorly differentiated blast cells
what are auer rods?
large, crystalline cytoplasmic inclusion bodies sometimes observed in myeloid blast cells during acute myeloid leukaemia
how is acute leukaemia diagnosed?
bone marrow aspirate (sample)
what leukaemia is most commonly seen in adults?
acute myeloid leukaemia
what is the FAB?
french-american-british scheme of classification of leukaemia based on morphology
M0-M5 FAB
immature forms of wbcs
M6 FAB
immature forms of erythrocytes
M7 FAB
immature platelets
define malignant haematopoiesis
uncontrolled proliferation of blood cell precursors/progenitors that fail to mature or show improper maturation.
what is the WHO scheme of classification of AML based on?
genetics
clinical features of acute leukaemia
anaemia - reduction of erythropoiesis
fever, malaise, infections - reduction of wbcs
bone pain
what is the wbc count in acute leukaemias?
increased to greater than 100,000/ micro L
how is leukaemia subtype determined?
immunological markers
what immunological markers allow identification of cells at varying stages of leukaemia?
cluster of differentiation markers (CD)
info on acute lymphoblastic leukaemia
accumulation of lymphoblasts in bone marrow
incidence off ALL highest at 3-7 years
most common leukaemia in children
acute leukaemia poorly differentiated cells
info on chronic leukaemias
malignant cells are well differentiated
identifiable by Romanowski staining procedure
info on chronic myeloid leukaemia
20% of all leukaemias
20-60 yrs old
malignant proliferation of granulocytes in bone marrow
characterised by presence of ph chromosome
what chromosome is present in CML?
Philadelphia chromosome
chronic myeloid leukaemia features
larger than usual platelets
PH chromosome
large no of myeloid cells
abnormally small chromosome - translocation of chromosome 22 to chromosome 9
what is a diagnostic indicator of CML
abnormally small chromosome - translocation of chromosome 22 to chromosome 9
chronic lymphocytic leukaemia info
male to female ratio 2:1
usually older than 40
splenomegaly and hepatomegaly
bruising
infections are common
chronic lymphocytic leukaemia features
anaemia caused later in disease
70-99% of cells are small mature lymphocytes
smear cells are common - fragile cells which are disrupted in blood film
what is hairy cell leukaemia?
subtype of CLL - abnormal B-lymphocytes in bone marrow