Haemopoiesis Flashcards
Sites of Haemopoiesis:
______:
- 0-2 months = ___ ___
- 2-7 months = ____, ____
- - months = bone marrow
Infants:
- ____ ______
Adults:
- ____ ______ (more restricted: in v______, ___, s______, skull, sacrum, _____, _____ ends)
Sites of Haemopoiesis:
Foetus:
- 0-2 months = yolk sac
- 2-7 months = liver, spleen
- 5-9 months = bone marrow
Infants:
- Bone marrow
Adults:
- Bone marrow (more restricted: in vertebrae, ribs, sternum, skull, sacrum, pelvis, femur ends)
Good pic for areas of haemopoiesis in folder.
Haemopoietic stem cell facts:
- self renewal ability
- unspecialised
- can differentiate/mature
- rare (1 in 1 million in bone marrow)
- _________ (in cell cycle G0) [only occasionally undergoes cell division]
Haemopoietic stem cell facts:
- self renewal ability
- unspecialised
- can differentiate/mature
- rare (1 in 1 million in bone marrow)
- Quiescent (in cell cycle G0) [only occasionally undergoes cell division]
_____ = the bone marrow environment that supports developing haemopoietic cell.
Stroma
generally is part of organ that is connective/structural
How can bone marrow be removed for inspection?
- _______
- ______
and briefly explain what they are.
- Aspirate (removes bone marrow fluid)
- trephine (removal of 1 or 2 cm of core bone)
Thalassaemia = [[ hereditary / acquired ]] condition which affects the [[ haem / globin chains ]] and causes abnormal formation of [[ RBCs / WBCs ]].
Thalassaemia = hereditary condition which affects the globin chains and causes abnormal formation of RBCs.
Clonality means the malignancies or pre-malignancies arrive from a _____ _______ ___.
Evidence for clonality:
- almost all lymphoproliferative disorders (from lymphoid lineage) and some AMLs (from myeloid lineage) carry a unique rearrangement of an
__________ or the ___ (_-___ ______) gene.
- almost all lymphoproliferative disorders (from lymphoid lineage) and some AMLs (from myeloid lineage) carry a unique rearrangement of an
- Women with leukaemia have clonal proliferation and all clonal cells will either have all _____ paternal or all ______ maternal _ _______. Remember females’ cell is XX and normally one is ________.
- Acquired cytogenetic/molecular changes that arise during development of malignancy exhibited by all clonal cells (eg _______ _________ in CML)
Clonality means the malignancies or pre-malignancies arrive from a single ancestral cell.
Evidence for clonality:
- almost all lymphoproliferative disorders (from lymphoid lineage) and some AMLs (from myeloid lineage) carry a unique rearrangement of an
immunoglobulin (antibody) or the TcR (T-cell receptor) gene.
- almost all lymphoproliferative disorders (from lymphoid lineage) and some AMLs (from myeloid lineage) carry a unique rearrangement of an
- Women with leukaemia have clonal proliferation and all clonal cells will either have all active paternal or all active maternal X-chromosomes. Remember females’ cell is XX and normally one is inactivated.
- Acquired cytogenetic/molecular changes that arise during development of malignancy exhibited by all clonal cells (eg Philadelphia translocation in CML = bcr-abl gene)
Myeloproliferative disorders (from myeloid lineage):
- polycythaemia rubra vera (too many ____ produced)
- _______ _________ (over production of platelets)
- ________ (neoplastic disorder of haemopoiesis causing ______ in the bone marrow which causes pancytopenia as a result)
These disorders are often associated with the ___ _____ mutation and the ________ mutation.
These myeloproliferative disorders have the potential to turn into ___.
Myeloproliferative disorders (from myeloid lineage):
- polycythaemia rubra vera (too many RBCs produced)
- essential thrombocytosis (over production of platelets)
- myelofibrosis (neoplastic disorder of haemopoiesis causing fibrosis in the bone marrow which causes pancytopenia as a result)
These disorders are often associated with the JAK2 V617F mutation and the calreticulin mutation.
These myeloproliferative disorders have the potential to turn into AML.
Essential Thrombocytosis:
- Platelets > ___ x10^9
- 50:50 JAK2 V617F and calreticulin mutation
- splenomegaly
- can transform into polycythaemia rubra vera or myelofibrosis
- can turn leukaemic
600
Risk groups for Essential Thrombocytosis:
Low risk:
- <40, no high risk features
- _____ or anti-platelet drug (e.g. _______)
Intermediate risk:
- 40-60, no high risk features
- _____ and ___________
High risk:
- > 60
- one or more high risk features: platelets > ____ x10^9, previous thrombosis, ______, _________.
Risk groups for essential thrombocytosis:
Low risk:
- <40, no high risk features
- aspirin or anti-platelet drug (e.g. clopridogrel)
Intermediate risk:
- 40-60, no high risk features
- aspirin and hydroxycarbamide
High risk:
- > 60
- one or more high risk features: platelets > 1500 x10^9, previous thrombosis, diabetes, hypertension.
Management of high risk Essential Thrombocytosis:
First line
= _____ + __________.
_________ is a ribonucleotide reductase inhibitor resulting in reduced ____________.
Second line
= _____ + _______.
_______ inhibits megakaryocyte differentiation.
Others = - \_\_\_\_, good for ET in preg - \_\_\_\_\_\_\_ - JAK2 inhibitors eg. \_\_\_\_\_\_
Management of high risk Essential Thrombocytosis:
First line
= aspirin + hydroxycarbamide.
Hydroxycarbamide is a ribonucleotide reductase inhibitor resulting in reduced deoxyribonucleotides.
Second line
= aspirin + anagrelide.
Anagrelide inhibits megakaryocyte differentiation.
Others = - IFN alpha, good for ET in preg - Busulfan - JAK2 inhibitors eg. ruxolitimab
Myelodysplastic syndromes.
Myelodysplastic syndromes (MDS) = characterised by ______ and ineffective haemopoiesis of > than, or = to, _ of the _______ series.
May have increased _________ cells.
Associated with acquired cytogenetic abnormalities: ________ _, _______ _, ______ _.
Characterised by progressive ___ _____ ______ and some progress to ___.
Myelodysplastic syndromes.
Myelodysplastic syndromes (MDS) = characterised by dysplasia and ineffective haemopoiesis of > than, or = to, 1 of the myeloid series.
May have increased myeloblast cells.
Associated with acquired cytogenetic abnormalities: monosomy 5, monosomy 7, trisomy 8.
Characterised by progressive bone marrow failure and some progress to AML.
Myelodysplatic syndrome features:
- mostly affects ______
- most present with ______ due to ______.
- can also present with _______ or _______
Myelodysplatic syndrome features:
- mostly affects elderly
- most present with fatigue due to anaemia.
- can also present with infections or bleeding.
Myelodysplastic syndrome management:
- blood and platelet _________.
- Growth factors: _________ (___) and _-___.
- chemotherapy, eg __________.
Myelodysplastic syndrome management:
- blood and platelet transfusion.
- Growth factors: erythropoietin (EPO) and G-CSF.
- chemotherapy, eg hydroxycarbamide.
Fanconi anaemia mutations cause:
- increased ____s which increase ___-_
- defective ________ maintenance
- “__-____ ______” causes altered response to DNA damage
- abnormal _______ _____ response
All of these lead to _____ _______.
Eventually leads to ______.
Fanconi anaemia mutations cause:
- increased MAPKs which increase TNF-alpha
- defective telomere maintenance
- “FA-BRCA pathway” causes altered response to DNA damage
- abnormal oxidative stress response
All of these lead to genetic instability.
Eventually leads to cancer.
Treatment of Fanconi anaemia:
- gold standard is _______ ___ ___ _______.
- Other: _________, surveillance for secondary _____.
Treatment of Fanconi anaemia:
- gold standard is allogeneic stem cell transplant.
- Other: corticosteroids, surveillance for secondary tumours.
Types of stem cell transplant:
- __________ transplant (_______) uses patients own stem cells.
- _________ transplant (_______) uses stem cells from another donor :
> _______ transplant, from identical twins
_______ sibling, HLA identical sibling
________ identical, a half matched family member (parent or half matched sibling)
_______ _______ ____ (VUD)
umbilical cord blood
Types of stem cell transplant:
- autologous transplant (‘autograft’) uses patients own stem cells.
- allogeneic transplant (‘allograft’) uses stem cells from another donor :
> Syngeneic transplant, from identical twins
Allogeneic sibling, HLA identical sibling
Haplotype identical, a half matched family member (parent or half matched sibling)
Volunteer unrelated donor (VUD)
umbilical cord blood
Autologous stem cell transplant:
- main indication are relapsed (Hodgkin’s + non-Hoodgkin’s) _______ and _______.
- stem cell harvested by _______ (a filtering system)
- patients receive _-____ to make stem cells leave bone marrow / mobilise
- ______ can be used to mobilise stem cells too
Autologous stem cell transplant:
- main indication are relapsed (Hodgkin’s + non-Hoodgkin’s) lymphoma and myeloma.
- stem cell harvested by apheresis (a filtering system)
- patients receive G-CSF to make stem cells leave bone marrow / mobilise
- Mozobil can be used to mobilise stem cells too
Allogeneic stem cell transplant:
- main indications are ________, relapsed ______, a______ a_____
- _________ chemotherapy = full intensity chemo which destroys bone marrow, done in preparation for a bone marrow transplant
- in malignant disease, an allograft has the benefit of graft vs leukaemia effect in addition to the effect of the high dose chemotherapy, but at the expense of graft vs host disease.
Allogeneic stem cell transplant:
- main indications are leukaemia, relapsed lymphoma, aplastic anaemia
- myeloablative chemotherapy = full intensity chemo which destroys bone marrow, done in preparation for a bone marrow transplant
- in malignant disease, an allograft has the benefit of graft vs leukaemia effect in addition to the effect of the high dose chemotherapy, but at the expense of graft vs host disease.
Non-myeloablative stem cell transplant:
- low dose, less toxic
- provide ____________ to allow donor cells to engraft
- graft-versus-leukaemia effect eradicates tumour
immunosuppression
Graft vs host disease:
- commonly manifests as ___, ______ or _______.
- <100 days is ____ and >100 days is _____
- immunosuppressive agents used to treat
Graft vs host disease:
- commonly manifests as rash, jaundice or diarrhoea.
- <100 is acute and >100 is chronic
- immunosuppressive agents used to treat
Graft vs leukaemia effect:
- the same cells which cause graft vs host, also attack remaining host leukaemia cells
- the graft contains donor T-cells which can help remove remaining cancerous cell (remember this is still at expense of graft vs host disease as these cells also attack the rest of the host)
- Therefore, strangely, you actually want more of a graft vs host effect as this will increase graft vs leukaemia effect. Less graft vs host increases chance of cancer relapse.
- this is why leukaemia relapse risk is higher in autologous transplant, because there is no graft vs host reaction.
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