Haem: Myeloproliferative, myelodysplastic etc

Question 1

Which cytokine helps in terminal T and B cell production in BM?

Answer 1

IL-7

Question 2

Which cytokine for megakaryocyte differentiation?

Answer 2

Thrombopoietin/IL-11

Question 3

Which exon mutation in JAK2 in IE vs PV?

Answer 3

IE - exon 12 (only sometimes)

PV - exon 14

Question 4

What can myeloproliferative disorders progress to?

Answer 4

AML or MF

Question 5

Name 5 MPN.

Answer 5

Polycythaemia vera (PV)
Essential Thrombocythaemia (ET)
Idiopathic Myelofibrosis
Idiopathic erythrocytosis
Chronic granulocytic leukaemia

Question 6

What are the features of the following in terms of differentiation and proliferation levels:
Leukaemia
MPN
MDS

Answer 6

Leukaemia - no differentiation, just proliferation
MPN - proliferation and differentiation
MDS - no differentiation, no proliferation

Question 7

What is low in PV?

Answer 7

EPO

Question 8

What GI feature is common in PV?

Answer 8

Peptic ulceration

Question 9

What is erythromelalgia?

Answer 9

Painful extremities

Question 10

What is the BM like in PV?

Answer 10

Hypercellular - fat spaces occupied by erythroid cells

Question 11

What test is used to rule out pseudopolycythaemia?

Answer 11

Isotope dilution test/Fick’s test
RBC with chromium
Plasma with iodine (binds albumin)

Question 12

What are the causes of a raised haematocrit without JAK2 mutation?

Answer 12

1. True polycythaemia (due to raised EPO e.g. hypoxia, renal tumour OR familial)
2. Pseudopolycythaemia

Question 13

What fibres are increased in BM in PV?

Answer 13

Reticulin fibres

Question 14

What is the tx of IE?

Answer 14

Venesection only to reduce RBCs

Question 15

What plt level suggests ET?

Answer 15

> 600x 10

Question 16

What age does ET occur at?

Answer 16

Bimodal - 30 and 55

Question 17

How does ET present?

Answer 17

Thrombosis or mucous bleeding

Question 18

What does the BM look like in ET?

Answer 18

Normal or slightly hypercellular

Question 19

What is the use of anagrelide in ET?

Answer 19

Antiplatelet - but not used much as accelerates myelofibrosis + palpitations/flushing,

No venesection used in ET.

Question 20

Briefly what happens in IMF?

Answer 20

BM fibrosis and extramedullary haematopoiesis

Question 21

Does IE progress to IMF?

Answer 21

No, only PV and ET

Question 22

What serious liver-related complication may occur in IMF?

Answer 22

Budd-Chiari syndrome

Question 23

What hypermetabolic features are seen in IMF?

Answer 23

Weight loss, fatigues, night sweats, hyperuricaemia

Question 24

What are the two stages of IMF?

Answer 24

Prefibrotic - looks like ET

Fibrotic

Question 25

What blood features are seen in IMF?

Answer 25

Tear drop poikilocytes Leukoerythroblastic picture Giant platelets Megakaryocytes

Question 26

What nucleated myeloid cells may be seen in the peripheries in IMF?

Answer 26

Basophils

Question 27

Rank the MPNs in terms of best to worst prognosis.

Answer 27

IE - no adverse effects ET - ~20yrs PV - 10 yrs IMF - 3-5yrs

Question 28

What is the normal Hb and Hct in females?

Answer 28

115-165 | 0.37-0.47

Question 29

What is the normal Hb and Hct in males?

Answer 29

130-180 | 0.4-0.54

Question 30

What causes pseudopolycythaemia?

Answer 30

Alcohol, obesity, diuretics

Question 31

What are the causes of polycythaemia which are Ph+ve?

Answer 31

CML

Question 32

What are the Ph-ve causes of polycythaemia?

Answer 32

PV ET MF

Question 33

What haematopoietic precursor is taregted in PV?

Answer 33

BFU-E

Question 34

Which myeloid neoplasms do not cause polycythaemia?

Answer 34

AML, myelodysplasia

Question 35

What are the causes of polycythaemia with raised EPO?

Answer 35

``` Appropriate: COPD CHD High altitude High affinity Hb ``` Inappropriate: Renal disease Uterine myoma Liver/lung tumours etc

Question 36

Compare the mutations present in PV, ET and IMF.

Answer 36

PV - JAK2 IMF - JAK2, calreticulin ET - JAK2, Calreticulin, MPL

Question 37

What is inactive EPO usually bound to in the cell?

Answer 37

JAK2

Question 38

Does IE have the JAK2 mutation?

Answer 38

No

Question 39

Name 2 causes of massive hepatosplenomegaly.

Answer 39

CML and MF

Question 40

Which scoring system is used for prognosis in MF?

Answer 40

DIPPS - score of 6 means 1.3yr survival

Question 41

Which JAK2 inhibitor may sometimes be used in MF with poor prognosis?

Answer 41

Ruxolotinib

Question 42

How does CML differ from PMF/PV/ET?

Answer 42

It is PhChr +ve

Question 43

What is the mutation causing CML?

Answer 43

BCR-ABL Ph Chr mutation (t (9; 22) --> Ph Chr)

Question 44

What is the FBC in CML?

Answer 44

Hb/plt normal or raised BUT massive leucocytosis

Question 45

What white cells may be characteristically found in CML?

Answer 45

Basophils, myelocytes and neutrophils (all mature)

Question 46

Which drug has drastically changed the prognosis with CML?

Answer 46

Imatinib

Question 47

What was the clinical course of CML before imatinib?

Answer 47

Chronic phase | Advanced phase: (1) accelerated (10-19% blasts), (2) blast crisis (>20% blasts)

Question 48

What is the MOA of imatinib?

Answer 48

ABL TK inhibitor

Question 49

How do you monitor Imatinib therapy?

Answer 49

RQ-PCR of % BCR-ABL transcripts

Question 50

What is a major molecular response in CML to imatinib?

Answer 50

3 log reduction in BCR-ABL i.e. <0.1% AT 18 MONTHS

Question 51

What are 2 SE of TK inhibitors?

Answer 51

Fluid retention | Pleural effusion

Question 52

Name a 2nd and 3rd gen TK inhibitor.

Answer 52

1st Gen – Imatinib 2nd Gen – Dasatinib, Nilotinib 3rd Gen – Bosutinib

Question 53

What is myelodysplasia?

Answer 53

Abnormal myeloid clone forms + number is reduced

Question 54

What can myelodysplasia transform to?

Answer 54

AML

Question 55

What is Pelger-Huet abnormality?

Answer 55

Bilobed neutrophils - characteristically seen in myelodysplastic syndromes

Question 56

What is the name for an increased number of mature hypersegmented neutrophils seen in MDS?

Answer 56

Myelokathexis

Question 57

What stain is used to see ringed sideroblasts in MDS?

Answer 57

Prussian blue (haemosiderin inside the mitochondria of erythroid precursors forms a ring around the RBS nucleus)

Question 58

Where are Auer rods seen?

Answer 58

In myeloblasts

Question 59

What is the FBC in myelodysplasia?

Answer 59

Everything low

Question 60

What is the prognostic index in MDS?

Answer 60

IPSS - takes into account %BM blasts, karyotype, Hb, plt, neutrophils

Question 61

Which mutations confer good prognosis in MDS?

Answer 61

del(11q), (5q), (12q) and (20q)

Question 62

Which mutation confers a poor prognosis in MDS?

Answer 62

del(7q)

Question 63

What is the prognosis with AML from MDS?

Answer 63

Very poor and usually not curable

Question 64

What are the causes of death in MDS?

Answer 64

1/3 each from: Infection Bleeding AML

Question 65

Which MDS treatments prolong survival?

Answer 65

Allo SCT | Intensive chemo

Question 66

What is the MOA of -CYTIDINES in MDS?

Answer 66

hypomethylating agents

Question 67

When is lenalidomide used in MDS?

Answer 67

In those with del(5q) (generally this confers a good prognosis)

Question 68

Which low-dose PO and SC chemo may be used in MDS?

Answer 68

Hydroxyurea(PO) and cytarabine (SC)