Haem Malignancies Flashcards
What is Haemato-oncology ?
study of cancers of the haematopoietic system
What does the acquisition of an oncogenic mutation within a haematopoietic cell generate ?
- a maligant clone
- the presence of this maligant clone negatively affects haematopoiesis
- inability to produce functional red & white blood cells is fatal
Describe Clonality
- clonal cells contain identical DNA copies
- initiating mutation occurs in one cell
- all daughter cells carry the same genetic mutation
What are some common features of haematological malignancies ?
- failure to produce effector cells
- maturational arrest
- increased rate of proliferation
- failure to undergo apoptosis
Describe Leukaemia
- presence of malignant cells in the peripheral blood & bone marrow
- classified by lineage & rate of progression
- myeloid & lymphoid
What is acute leaukaemia characterised by ?
- accumulation of immature cells = maturational arrest
- ‘blasts’
- increased rate of proliferation
- clinically aggressive disease
What is chronic leaukaemia characterised by?
- failure to undergo apoptosis
- less aggressive disease
- bone marrow tumour - site of haematopoiesis is also tumour site
- suppression of ‘normal’ clone
Describe Lymphoma
- Lymphoid malignancy
- malignant cell can be B, T or NK cell
- classified by rate of progression & presence of Reed-Sternberg cells
- low grade = slowly proliferating malignant cells
- high grade = rapidly proliferating maligant cells & clinically aggressive disease
Describe Hodgkin Lymphoma
- presence of Reed-Sternberg cells
- mature B cell maligancy
- failure to undergo apoptosis
Describe Non-Hodgkin Lymphoma
- diverse group of malignant diseases
- mature B, T or NK cell malignancies
- failure to undergo apoptosis
Describe the Leukaemic phase
- malignant cells enter the peripheral circulation
-appear in the bone marrow - continue to proliferate in the bone marrow
Describe Myelodsyplastic Syndrome
- myeloid malignancy
- increased proliferation of precurso cells within bone marrow
- maturational arrest
- premature death - ineffective haematopoiesis
- suppression of ‘normal’ clone
Describe Multiple Myeloma
- lymphoid malignancy
- mature B cells - plasma cells
- increased proliferation
- failure to undergo apoptosis
- increased monoclonal antibody conc. in blood
- suppression of haematopoiesis
Describe Myeloproliferative Neoplasms
- myeloid lineage
- increased rate of proliferation
- Polycythemia - accumulation of mature erythrocytes
- essential thrombocythemia - accumulation of megakaryocytes
- suppression of haematopiesis
Describe Bone marrow sampling - Aspirate
- Bone marrow film = morphological assessment of cells
- minimal residual disease monitoring
- cytogenetics - assessment of chromosomal abnormalities
Describe Bone marrow sampling - Trephine Biopsy
- processed for histology
- IHC - cell marker analysis
- allows for assessment of bone marrow architecture & cell morphology
How is flow cytometry used to diagnose haem malignancies ?
- cells labelled with fluorescent antibodies to detect specific cell markers
- pattern of staining confirms cell lineage & stage of development
- differentiates between myeloid & lymphoid cells
- differentiates between species of cells
- differentiates between intermediate stages of development of cells
- confirms diagnosis
Describe Cytogenetics
- assessment of Karyotype
- investigation of chromosomal abnormalities
- clonal disease - all cells contain same abnormality
- prognostic indicator
Define Euploid
- somatic cell - 46 chromosomes
Define Karyotype
- each cell contains 23 pairs of chromosomes
- 46 single chromosomes
Define Aneuploidy
loss or gain of chromosomes
Define Translocation
- exchange of genetic material between chromosomes
Define Monosomy
- condition where someone only has one of a pair of chromosomes
Define Trisomy
- condition where the affected person has 3 copies of 1 chromosome instead of 2
