Haem: Myeloproliferative, myelodysplastic etc Flashcards
Which cytokine helps in terminal T and B cell production in BM?
IL-7
Which cytokine for megakaryocyte differentiation?
Thrombopoietin/IL-11
Which exon mutation in JAK2 in IE vs PV?
IE - exon 12 (only sometimes)
PV - exon 14
What can myeloproliferative disorders progress to?
AML or MF
Name 5 MPN.
Polycythaemia vera (PV) Essential Thrombocythaemia (ET) Idiopathic Myelofibrosis Idiopathic erythrocytosis Chronic granulocytic leukaemia
What are the features of the following in terms of differentiation and proliferation levels:
Leukaemia
MPN
MDS
Leukaemia - no differentiation, just proliferation
MPN - proliferation and differentiation
MDS - no differentiation, no proliferation
What is low in PV?
EPO
What GI feature is common in PV?
Peptic ulceration
What is erythromelalgia?
Painful extremities
What is the BM like in PV?
Hypercellular - fat spaces occupied by erythroid cells
What test is used to rule out pseudopolycythaemia?
Isotope dilution test/Fick’s test
RBC with chromium
Plasma with iodine (binds albumin)
What are the causes of a raised haematocrit without JAK2 mutation?
- True polycythaemia (due to raised EPO e.g. hypoxia, renal tumour OR familial)
- Pseudopolycythaemia
What fibres are increased in BM in PV?
Reticulin fibres
What is the tx of IE?
Venesection only to reduce RBCs
What plt level suggests ET?
> 600x 10
What age does ET occur at?
Bimodal - 30 and 55
How does ET present?
Thrombosis or mucous bleeding
What does the BM look like in ET?
Normal or slightly hypercellular
What is the use of anagrelide in ET?
Antiplatelet - but not used much as accelerates myelofibrosis + palpitations/flushing,
No venesection used in ET.
Briefly what happens in IMF?
BM fibrosis and extramedullary haematopoiesis
Does IE progress to IMF?
No, only PV and ET
What serious liver-related complication may occur in IMF?
Budd-Chiari syndrome
What hypermetabolic features are seen in IMF?
Weight loss, fatigues, night sweats, hyperuricaemia
What are the two stages of IMF?
Prefibrotic - looks like ET
Fibrotic
What blood features are seen in IMF?
Tear drop poikilocytes
Leukoerythroblastic picture
Giant platelets
Megakaryocytes
What nucleated myeloid cells may be seen in the peripheries in IMF?
Basophils
Rank the MPNs in terms of best to worst prognosis.
IE - no adverse effects
ET - ~20yrs
PV - 10 yrs
IMF - 3-5yrs
What is the normal Hb and Hct in females?
115-165
0.37-0.47
What is the normal Hb and Hct in males?
130-180
0.4-0.54
What causes pseudopolycythaemia?
Alcohol, obesity, diuretics
What are the causes of polycythaemia which are Ph+ve?
CML
What are the Ph-ve causes of polycythaemia?
PV
ET
MF
What haematopoietic precursor is taregted in PV?
BFU-E
Which myeloid neoplasms do not cause polycythaemia?
AML, myelodysplasia
What are the causes of polycythaemia with raised EPO?
Appropriate: COPD CHD High altitude High affinity Hb
Inappropriate:
Renal disease
Uterine myoma
Liver/lung tumours etc
Compare the mutations present in PV, ET and IMF.
PV - JAK2
IMF - JAK2, calreticulin
ET - JAK2, Calreticulin, MPL
What is inactive EPO usually bound to in the cell?
JAK2
Does IE have the JAK2 mutation?
No
Name 2 causes of massive hepatosplenomegaly.
CML and MF
Which scoring system is used for prognosis in MF?
DIPPS - score of 6 means 1.3yr survival
Which JAK2 inhibitor may sometimes be used in MF with poor prognosis?
Ruxolotinib
How does CML differ from PMF/PV/ET?
It is PhChr +ve
What is the mutation causing CML?
BCR-ABL Ph Chr mutation (t (9; 22) –> Ph Chr)
What is the FBC in CML?
Hb/plt normal or raised BUT massive leucocytosis
What white cells may be characteristically found in CML?
Basophils, myelocytes and neutrophils (all mature)
Which drug has drastically changed the prognosis with CML?
Imatinib
What was the clinical course of CML before imatinib?
Chronic phase
Advanced phase: (1) accelerated (10-19% blasts), (2) blast crisis (>20% blasts)
What is the MOA of imatinib?
ABL TK inhibitor
How do you monitor Imatinib therapy?
RQ-PCR of % BCR-ABL transcripts
What is a major molecular response in CML to imatinib?
3 log reduction in BCR-ABL i.e. <0.1% AT 18 MONTHS
What are 2 SE of TK inhibitors?
Fluid retention
Pleural effusion
Name a 2nd and 3rd gen TK inhibitor.
1st Gen – Imatinib
2nd Gen – Dasatinib, Nilotinib
3rd Gen – Bosutinib
What is myelodysplasia?
Abnormal myeloid clone forms + number is reduced
What can myelodysplasia transform to?
AML
What is Pelger-Huet abnormality?
Bilobed neutrophils - characteristically seen in myelodysplastic syndromes
What is the name for an increased number of mature hypersegmented neutrophils seen in MDS?
Myelokathexis
What stain is used to see ringed sideroblasts in MDS?
Prussian blue (haemosiderin inside the mitochondria of erythroid precursors forms a ring around the RBS nucleus)
Where are Auer rods seen?
In myeloblasts
What is the FBC in myelodysplasia?
Everything low
What is the prognostic index in MDS?
IPSS - takes into account %BM blasts, karyotype, Hb, plt, neutrophils
Which mutations confer good prognosis in MDS?
del(11q), (5q), (12q) and (20q)
Which mutation confers a poor prognosis in MDS?
del(7q)
What is the prognosis with AML from MDS?
Very poor and usually not curable
What are the causes of death in MDS?
1/3 each from:
Infection
Bleeding
AML
Which MDS treatments prolong survival?
Allo SCT
Intensive chemo
What is the MOA of -CYTIDINES in MDS?
hypomethylating agents
When is lenalidomide used in MDS?
In those with del(5q) (generally this confers a good prognosis)
Which low-dose PO and SC chemo may be used in MDS?
Hydroxyurea(PO) and cytarabine (SC)
