Haemopoietic System Malignancies

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Mind Map by , created over 6 years ago

Blood Science Mind Map on Haemopoietic System Malignancies, created by maisie_oj on 04/30/2013.

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Created by maisie_oj over 6 years ago
Haematopoietic System Malignancies 2
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Haemostasis (part 2: secondary haemostasis)
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Bone marrow failure syndromes
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Spanish Conversation Phrases
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Core 1.12 Timbers blank test
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Cell adaptations
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Acute Inflammation
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Rheumatoid Arthritis
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Blood transfusion and haematopoietic stem cell transplantation
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Haemostasis (part 1: primary haemostasis)
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Haemopoietic System Malignancies
1 Haemopoietic stem cells
1.1 Progenitor cells
1.1.1 Mature blood cells
1.1.1.1 Lymphoid Progentior
1.1.1.1.1 B cells
1.1.1.1.1.1 Plasma cells
1.1.1.1.1.2 B cell lineage lymphomas, myeloma, chronic lymphocytic leukaemia, Hodgkins disease
1.1.1.1.2 T cells
1.1.1.1.2.1 T lineage lymphomas (less common than B)
1.1.1.1.3 NK cells
1.1.1.1.4 Pre B acute lymphoblastic leukaemia, T lineage precursor acute lymphoblastic leukaemias
1.1.1.2 Myeloid Progenitor
1.1.1.2.1 Erythrocyte
1.1.1.2.2 Megalokarocyte
1.1.1.2.2.1 Platelets
1.1.1.2.3 Neutrophil
1.1.1.2.4 Eosinophil
1.1.1.2.5 Basophil
1.1.1.2.6 Acute myeloid leukaemia
1.1.2 Lifespan-months (short)
1.2 Cannot survive without
1.3 Chronic myeloid leukaemia, myelodysplastic syndromes, acute myeloid leukaemias
2 Leukaemia
2.1 'White blood'
2.2 2 types
2.2.1 Acute leukaemia
2.2.1.1 Accumulation of blasts (undifferentiated cells) in bone marrow/blood
2.2.1.2 2 types
2.2.1.2.1 Acute myeloid leukaemia - cells derived from haematopoietic stem cells/myeloid progenitors
2.2.1.2.1.1 More common in older people - peak 80-84
2.2.1.2.2 Acute lymphoblastic leukaemia - cells derived from lymphoid precursors
2.2.1.2.2.1 Childhood leukaemia - most common 5-9 yo
2.2.1.3 Indices bone marrow failure - reduced production of blood cells
2.2.1.3.1 Red blood cells - anaemia
2.2.1.3.2 Platelets - spontaneous bleeding - death
2.2.1.3.3 Neutrophils - neutropenic sepsis - death
2.2.1.3.4 Can present with infiltration by proliferating blasts - less common (usually in blood)
2.2.1.3.5 Other symptoms - lymphadenopathy, fevers, bone pain
2.2.1.4 Diagnosis by immunophenotyping
2.2.1.4.1 Morphology is not reliable - all look the same
2.2.2 Chronic myeloid leukaemia
2.2.2.1 Myeloproliferative disease
2.2.2.2 High white blood cell count - cells differentiate and function normally
2.2.2.2.1 Increased neutrophils and myelocytes (neutrophil precursor)
2.2.2.3 Causes splenomegaly (pain and satiety), weight loss and fevers
2.2.2.4 Deaths are due to transformation to acute leukaemia (blast crisis)
2.2.2.4.1 WBCs stop differentiating and cannot function
2.2.2.5 50% are dead by 4 years
2.2.2.6 Philadelphia chromosome is diagnostic of CML (can occur in acute too)

Annotations:

  • See Philadelphia Chromosome section of cancer lecture for more detail
2.2.2.6.1 Karocyte always tested if CML is a possibility
2.2.2.6.1.1 G-banding - cells in metaphase stained with giemsa
2.2.2.6.2 Bcr/Abl tyrosine kinase causes
2.2.2.6.2.1 Cell proliferation via JAK/STAT and MAPK pathway in the nucleus
2.2.2.6.2.2 Cell proliferation, survival and differentiation via JAK/STAT and BCL2 family
2.2.2.6.2.3 Increased motility, decreased adhesion via Paxillin
2.2.2.7 Imantinib (Gleevec) blocks Bcr/Abl ATP site - inhibits tyrosine kinase activity
2.2.2.7.1 Only a few side effects - rash, cramps, oedema, tiredness
2.2.2.7.2 93% of patients had no blast crisis within 4 years
3 Immunophenotyping
3.1 Antibody with green fluorescent conjugate binds to specific cell protein (e.g. CD10)
3.2 Different antibody with red fluorescent conjugate binds to another cell protein (e.g. CD22)
3.3 Cells passed through flow cytometer - flow single file
3.3.1 Laser shines light onto cells
3.3.1.1 Fluorescent proteins emit light of different wavelengths (colours)
3.3.1.1.1 Each colour detected by a different channel
3.3.1.1.1.1 Results shown on graph
4 Genetic Testing
4.1 Routine in acute leukaemia diagnosis and management
4.2 Cytogenetics - chromosome structure
4.2.1 G-banding
4.2.1.1 Cells cultured and metaphase spreads made
4.2.1.1.1 Karyotype analysed
4.2.2 FISH
4.2.2.1 Cells don't need to be in metaphase
4.2.2.2 Can see the presence of specific loci using different fluorescent markers
4.2.3 Cytogenetic abnormalities affect prognosis
4.2.4 t(12;21) is a good marker for ALL
4.2.4.1 Philadelphia chromosome and t(4;11) are bad markers - also seen in CML
4.3 Point Mutations
4.4 Half of all AML has normal G-banding/cytogenetic analysis results
4.4.1 Smaller lesions not detectable by cytogenetics.FISH
4.4.2 Falini 2005
4.4.2.1 61% of normal karyotype AML has a mutated nucleophosmin gene
5 Genetic Lesions
5.1 Balanced Translocations
5.1.1 8-21 causes AML1-ETO fusion
5.1.1.1 AML1 (RUNX1) is a transcription factor on 21, involved in haematopoietic differentiation
5.1.2 9-11 causes MLL-MLLT3 fusion
5.1.2.1 MLL is a histone methyltransferase on chromosome 11, involved in epigenetic regulation
5.2 Mutations
5.2.1 CEBPA, WT1, RUNX1 all transcription factors
5.2.2 DNMT3A, TET2, MLL-PTD, ASXL1 all involved in epigenetic regulation
5.2.3 FLT3, KIT are receptor tyrosine kinases
6 Acute Leukaemia Treatment
6.1 Risk is determined based on cytogenetics and mutations
6.1.1 Low risk - 4 cycles of intensive chemotherapy
6.1.1.1 Multi-drug treatment
6.1.2 Intermediate/High risk - chemotherapy until remission and then an allogeneic transplant
6.1.2.1 Remission = normal bone marrow and reversal of bone marrow failure
6.2 No new drugs since 1960/70s
6.2.1 Daunorubicin (red) and Cytarabine (clear)
6.3 AML cells disappear after 2 weeks of constant RBC and platelet transfusions with antibiotics
6.3.1 Neutrophil count doesn't increase until much later
6.4 Allogeneic transplant uses graft vs host reaction to kill remaining cancer cells
6.4.1 Very unpredictable - can be fatal
6.5 80% of children can be cured, adults don't do as well

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