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.
