11.6 Chronic Myeloid Leukaemia & Overview of Myeloproliferative Neoplasms & Aplastic Anaemia

Question 1

Briefly summarise chronic myeloid leukaemia

Answer 1

• Unregulated proliferation of myeliod cells in bone marrow
• Increased mature granulocytes (mostly neutrophils) in blood

Question 2

What translocation mutation causes Chronic Myeloid Leukaemia? What is it called?

Answer 2

• Translocation of long arms of chromosomes 9 and 22.
• Called “Philadelphia Chromosome”

Question 3

Who is more at risk for Chronic Myeloid Leukaemia: Men or women?

Answer 3

Men

Question 4

Describe how production of a Philadelphia Chromosome leads to uncontrolled cell proliferation

Answer 4

• On normal Chromosome 9, ABL gene is regulated by an end cap
• When translocated to Chromosome 22 alongside the BCR promoter, this control is lost.
• This causes uncontrolled proliferation, cell adherence, and downregulation of apoptosis

Question 5

Chronic Myeloid Leukaemia is frequently asymptomatic, but can sometimes present with symptoms. What are some common symptoms?

Answer 5

• Constitutional Sx: fatigue, weight loss
• Extramedullary haematopoiesis: splenomegaly

Question 6

What are some rarer symptoms of Chronic Myeloid leukaemia (i.e. not splenomegaly)?

Answer 6

• Leukostasis -> dypsnoea, headache, visual disturbances
• CVA, MI, DVT

Question 7

What is leukostasis

Answer 7

The formation of white blood cell plugs in microvasculature

Question 8

CBE/blood smear findings in chronic myeloid leukaemia

Answer 8

• Neutrophilia
• <10% blasts in circulation
• Basophilia and eosinophilia
• Thrombocytosis
• normocytic/chromic anaemia

Question 9

Expected bone marrow biopsy findings in chronic myeloid leukaemia

Answer 9

• Hypercellularity
• Normal/slightly elevated marrow blast %

Question 10

Expected karyotype findings in CML

Answer 10

Presence of philadelphia 9-22 translocation

Question 11

What is the gold-standard test for chronic myeloid leukaemia? How does it work?

Answer 11

• Reverse transcriptase PCR
• Convert RNA to DNA
• Amplify specific sections of DNA to test for presence of BCR-ABL gene

Question 12

How can Fluorescent in-situ hybridisation be used to identify the BCR-ABL gene

Answer 12

• Assign a different coloured probe to each of them
• If the colours overlap to form a new colour, they are together, and the translocation is present

Question 13

Expected survival of chronic/accelerated/blast phase leukaemia

Answer 13

• Chronic: 4-6 years
• Accelerated: Up to 1 year
• Blast phase: 3-6 months

Question 14

How do tyrosine kinase inhibitors help with CML?

Answer 14

• Block substrate from BCR-ABL proteins
• Prevents downstream signalling
• Cell proliferation/apoptosis is unaffected

Question 15

What characterises polycthemia vera?

Answer 15

Increased RBC level, INDEPENDENT OF EPO LEVEL

Question 16

What mutation causes polycythemia vera?

Answer 16

JAK2 mutation

Question 17

What reactive causes must be excluded before we can diagnose essential thrombocytosis?

Answer 17

• Inflammation
• Splenectomy
• Iron deficiency anaemia

Question 18

What mutations are known to occur alongisde essential thrombocytosis?

Answer 18

• JAK2
• CALR
• MPL

Question 19

Are polycythemia vera and essential thrombocytosis more common in men or women?

Answer 19

Women

Question 20

Describe myelofibrosis

Answer 20

1. Increased clonal megakaryocyte proliferation
2. Excess fibroblast growth factor
3. Marrow fibrosis and extramedullary haematopoiesis

Question 21

Which demographic is most likely to get myelofibrosis?

Answer 21

Men >50 years old

Question 22

What does bone marrow biopsy look like for myelofibrosis

Answer 22

“cellular streaming”

Question 23

What does bone marrow biopsy look like for essential thrombocytosis?

Answer 23

Large numbers of poikilocytotic megakaryocytes

Question 24

What is the JAK2 gene responsible for? What can JAK2 mutation cause?

Answer 24

• JAK2 encodes for cytoplasmic tyrosine kinase
• Mutation leads to hypersensitivity to cytokines and EPO-independent erythropoiesis

Question 25

Myelodisplastic syndromes are characterised by:

Answer 25

• Cytopenias
• Dysplasia in one or more lineages
• Ineffective haematopoiesis

Question 26

What is the maximum bone marrow blast percentage for myelodysplassia. What is it called if this is exceeded?

Answer 26

• Cutoff is <20%
• If exceeded, becomes acute myeloid leukaemia

Question 27

In what % of myelodysplasia cases do we see recurrent genetic abnormalities/

Answer 27

40-50%

Question 28

What is aplastic anaemia? What characterises it?

Answer 28

• Bone marrow failure; normal haematopoiesis inadequate
• Characvterised by peripheral cytopenia and bone marrow hypoplasia

Question 29

List some ways in which chemical and physical damage can cause aplastic anaemia

Answer 29

• Cytotoxic drugs
• Radiation
• Benzene

Question 30

List some ways in which immune destruction can cause aplastic anaemia

Answer 30

• Idiopathic
• Eosinophilic fasciitis

Question 31

List one way in which constituional genetic defects can cause aplastic anaemia

Answer 31

• Telomere diease