MPN, MDS & MDS/MPN Flashcards
Describe myeloproliferative neoplasms (MPN) aka myeloproliferative disorders (MPD) & clinical characteristics (consequence/resulting)
- Clonal stem cell disorder of HC
- result in inc. production of cells & inc [cells in PB]
- in BM haematopoiesis
- extra-medullary hematopoiesis
- inc. thrombotic & hemorrhagic events
Sub-categories of MPN
- Chronic myeloid leukaemia
- Polycythaemia vera
- Primary myelofribrosis
- Essential thrombocytopenia
Describe the pathophysiology of Chronic Myeloid Leukaemia (CML) [caused by]
- Caused by formation of Philadelphia chromosome (Ph1): translocation of CHromo 9 & 22
=> BCR-ABL1 fusion gene - BCR-ABL1+ = diagnostic criteria for CML
2 phases of CML
- Accelerated phase: 10-19% blast in PB or BM
2. Blast phase: >20% blast in PB = acute leukaemia. *predominantly myeloid blast
Describe what Polycythaemia Vera (PV) is
- well-differentiated haematopoietic neoplasia of RBC
- Excess production of RBC => inc RBC mass
- mostly in 50-60yrs old
1. Pre Polycythaemic phase
2. Overt “ “
3. Post “ “ => anaemia
Pathophysiology of PV
- JAK2V617F point mutation in position 1849 of exon 14 of Janus Kinase gene => G–>T (Val -> Phe)
Diagnostic criteria of PV in major & minor criteria
MAJOR 1. Hb > 165g/L (M) or >160 (F) 2. BM trilineage hyperplasia 3. JAK2V617F/JAK2 exon12 mutation MINOR - Dec. [Epo] (bc neg FB from inc RBC)
Describe Essential Thrombocythaemia
- welll differentiated neoplasm of plts/MK
- Dx based on [plts], BM characteristics, JAK2 mutation
Describe Primary myelofibrosis
- JAK2V617F
- 2 phases: Pre-fibrotic & fibrotic
Describe Myelodysplatic Syndromes (MDS)
- Simultaneous proliferation & apoptosis of cells in BM =>ineffective haematopoesis
- one or + cell line affected
- Dysplagia (abnormal morphology) detected
- Caused 1º (naturally) or 2º (after chemo/radiation therapy)
What to expect when viewing BM in MDS
- ringed sideroblast (iron deposits)
- marked anisocytosis in RBC & MK/plts
- NUclear abnormalities in RBC, granulocytes, MK/plts
- presence of blas
cytopenia is defined as*
- Anaemia <100 g/L
- Thrombocytopenia < 100 x10^9 /L
- Neutropenia <1.8 x 10^9 /L
Describe MDS/MPN
- clonal haematopoetic neoplasms
- dysplastic & proliferative neoplasms
- e.g Chronic myelomonocytic leukaemia (CMML)
Subcategories of CMML & differences
- CMML-1: <5% blast in PB & <10% blast in BM
- CMML-2: 5-19% blast in PB & <10-19% blast in BM
most common mutated genes in MDS is
SF3B1
