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Haematological malignancies (Multiple myeloma (Lymphoid malignancy, Mature…
Haematological malignancies
Clonality
If a progenitor cell acquires oncogenic mutation to a degree with survival benefit, then every cell will have the same mutation as they are clones
Overview
Haemato-oncology is the study of cancers of the haematopoietic system.
Acquisition of an oncogenic mutation within a haematopoietic cell generates a malignant clone.
The presence of this malignant clone negatively affects haematopoiesis.
Inability to produce functional red and white blood cells is fatal.
Malignant features
malignant cell will try to continue purpose but may fail to produce effector cells
unable to fully progress through maturity (maturational arrest)
more rapid growth = more aggressive
Failure to undergo apoptosis
Leukaemia (acute)
Maturational arrest
myeloblast is an immature myeloid cell
ireegular nucleus shape 'scanty' cytoplasm
Increased rate of proliferation
Leukaemia (chronic)
Failure to undergo apoptosis
less aggressive disease
BM tumour site
malignant clone can outcompete healthy haematopoeitic cells
Lymphoma
Lymphoid malignancy
solid lymphoid tumour within the secondary organs
malignant cell can be B-cell, T-cell or NK-cell
Classified by rate of progression and presence of reed-sternberg cells
Hodgkin lymphoma
Presence of Reed-Sternberg cells - nuclei are mirror images
Mature B-cell malignancy - restricted to B-cells only
Failure to undergo apoptosis
Non-Hodgkin Lymphoma
Diverse group of malignant diseases
Mature B-cell, T-cell or NK-cell malignancies
all other lymphhomas
Leukaemic phase
Malignant cells enter the peripheral circulation from solid tumour
Appear in the BM
Continue to proliferate within the BM
Once BM is infiltrated haematopoeisis is suppressed along with normal clone
Myelodysplastic syndrome
Myeloid malignancy
Increased proliferation of precursor cells within the bone marrow
Maturational arrest
Premature death – ineffective haematopoiesis
BM hyper-cellularity
Suppression of haematopoiesis
Suppression of ‘normal’ clone
Multiple myeloma
Lymphoid malignancy
Mature B cells – plasma cells
Increased monoclonal antibody concentrations in blood
Increased proliferation
Failure to undergo apoptosis
BM Accumulation
Suppression of haematopoiesis
Suppression of the ‘normal’ clone
Myeloproliferstive neoplasms
Myeloid lineage
Increased rate of proliferation
Polycythemia – accumulation of mature erythrocytes
Essential thrombocythemia – accumulation of megakaryocytes
Suppression of haematopoiesis
Suppression of the ‘normal’ clone