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Haematology > Myeloid Malignancy > Flashcards

Myeloid Malignancy Flashcards

1
Q

Where do mutational events occur leading to myeloid malignancies?

A

In haematopoietic stem cell or in the early (more committed) myeloprogenitor cell

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2
Q

A mutation in the haemopoetic stem cell leading to leukaemia produced a cell called what?

A

Leukaemic stem cell

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3
Q

What are the two vital jobs of the HPSC?

A

Self-renewal and multipotentiality

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4
Q

How is self-renewal different in AML?

A

Early progenitor cells should lose their ability to self-renew in health, but instead they behave more like stem cells due to mutations and are able to self-renew
BUT differentiate is blocked –> population grows replacing the normal haematopoietic stem cells

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5
Q

What are the features of AML?

A

Bone marrow failure

anaemia, thrombocytopenic bleeding (purpura/mucosal membrane), infection (due to neutropenia, mostly bacterial/fungal

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6
Q

What is the appearance of the bone marrow in acute leukaemia?

A

Absolutely packed with blast cells (buried within this are leukaemic stem cells driving this)

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7
Q

What is a big confluent area of thrombocytopenic bleeding in the skin called?

A

Ecchymosis

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8
Q

What investigations should you do if you suspect AML?

A

Blood count, blood film (WCC high/low, neutropenia, thrombocytopenia, low Hb)
Bone marrow aspirate (will confirm diagnosis)/trephine
Cryptogenetics (karyotype) from leukaemic balsts
Immunophenotyping of leukaemic blasts (can distinguish between myeloblasts/lymphoblasts)
CSF examination if symptoms (e.g. headache, cranial n palsy)
Targeted molecular genetics for associated acquired gene mutations

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9
Q

What must you see on bone marrow aspiration to confirm AML diagnosis?

A

> 20% blasts

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10
Q

What associated acquired gene mutations might you test for?

A

FLT3 (poor prognosis), NPM1 (better prognosis), IDH 1 and 2 (enzymes of kreb cycle that can become leukogenic)

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11
Q

How do you treat AML?

A

Supportive care (platelets, transfusion, antibx, antifungals if needed etc.)
Anti-leukaemic chemotherapy (induction and consolidation)
Use danorubicin and cytosine arabinoside
Allogenic stem cell transplantation (recognises leukaemia as foreign and kills it)
All-trans retinoic acid and arsenic trioxide in low risk acute promyelocytic leukaemia

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12
Q

What targeted treatments can be used for AML?

A

Midostaurin in FLT3 mutated AML

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13
Q

What is the new targeted antibody treatment in AML?

A

Mylotarg

Binds to CD33 antigen on leukaemic cells, if internalised and releases molecules that damage DNA

But drug pump on leukaemic cell can release these –> damage to other cells

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14
Q

What is chronic myeloid leukaemia?

A

Mutation in HPSC with excessive proliferation in the myeloid lineage (esp granulocytes)

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15
Q

What are the features of CML?

A

Anaemia (bone marrow failure, cytokine supressing haemostasis, hepicidin)
Splenomegaly (due to infiltration)
Weight loss (sweat a lot due to huge cell burden)
Hyperleukostasis - fundal haemorrhage, venous congestion, altered consciousness, respiratory failure
Gout

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16
Q

Why must you not transfuse blood in CML patients?

A

Anaemia is protective as there is hyperleukostasis

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17
Q

What would be a typical blood count in CML?

A

High WBC, low Hb, often high platelets, high neutrophils and monocytes, eosinophils, basophils etc.

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18
Q

What is the appearance of the blood film in CML?

A

lots of white cells, with myelocytes and metamyelocytes

19
Q

What are the lab features of CML?

A

High WCC, platelets, anaemia, blood film with all stages of white cell differentiation with increased basophils
Bone marrow hypercellular
Philadelphia chromosome present

20
Q

What is the Philadelphia chromosome?

A

A translocation between chromosome 9 and 11 leading to a BCR-ABL fusion which is present in a lot of CML

21
Q

What is involved in the treatment of CML?

A

Tyrosine kinase inhibitors, e.g. glivec
(direct inhibitors of the BCR-ABL gene)
Allogenic transplantation in TKI failure

22
Q

How do the tyrosine kinase inhibitors work?

A

ABL-BCR gene activates downstream uncontrolled downstream signalling through phospholyation but the TKIs bind to the kinase domain and block CML essentially

23
Q

What are myelodysplastic syndromes?

A

Acquired clonal disorders of bone marrow

Seen in elderly

24
Q

What is the typical presentation of MDS?

A

Elderly, may present as macrocytic anaemia and pancytopenia

25
Q

Why might we worry about MDS?

A

They are pre-leukaemic

May be fatal as a result of bone marrow failure or AML (1/3rd progress to AML)

26
Q

How do you treat MDS?

A

Supportive

Stem cell transplantation for young patients

27
Q

What are the three myeloproliferative neoplasms?

A

Polycythaemia vera
Essential thrombocythaemia
Idiopathic myelofibrosis

28
Q

What are the myeloproliferative neoplasms a result of?

A

Over proliferation of differentiated cells

29
Q

What is PV an excess of?

A

Red cells

30
Q

What is ET an excess of?

A

platelets

31
Q

What mutation tends to be present in these myeloproliferative neoplasms?

A

JAK2

95% in PV, 50% in ET and myelofibrosis

32
Q

What is JAK2?

A

Tyrosine kinase linked to a cell surface receptor
Stimulated by no of cytokines, incl. erythropoietin
In mutation of JAK2 - doesn’t need signal * open all the time, independent on cytokines

33
Q

What are the clinical features of PV?

A 
Headaches
Itch 
Vascular occlusion 
Thrombosis
TIA, stroke
Splenomegaly 
(all due to increased viscosity/reduced O2 delivery)
34
Q

What are the lab features of PV?

A

Raised Hb and haematocrit
Tend to also have raised WCC/platelets
Raised uric acid
Inc. in red cell mass

35
Q

What is haematocrit?

A

% of blood that is red cells

usually 45%

36
Q

What anaemia are patients with PV at risk of?

A

Iron deficiency anaemia

37
Q

How do you treat PV?

A

Venesection and aspirin

?hydroxycarbamide 
JAK2 inhibitors (e.g. ruxolitinib) if HC failure and systemic symptoms
38
Q

What is the natural history of PV?

A

Stroke/venous thromboses if poorly controlled
Bone marrow failure from development of secondary myelofibrosis
Transformation to AML

NB - if really high risk will need treatment with HC etc.

39
Q

What is ET?

A

Myeloproliferative disease with predominant feature of raised platelet count

40
Q

What mutations tend to occur in ET?

A

JAK3 (50%)

CALR (calreticulin) 25%

41
Q

What symptoms are associated with ET?

A

Arterial/venous thromboses, digital ischaemia, gout, headache, splenomegaly

42
Q

How do you treat ET?

A

Aspirin, hydroxycardbamide or anagrelide (platelet inhibitor)

43
Q

What can ET progress to?

A

Myelofibrosis/AML

Haematology (14 decks)

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