4.3 Chronic Myeloproliferative Disorders Flashcards Preview

Block 5 > 4.3 Chronic Myeloproliferative Disorders > Flashcards

Flashcards in 4.3 Chronic Myeloproliferative Disorders Deck (25):
1

What is the term for too much red, ahite and platelets?

red: Polycythaemia
White: Leukocytosis
Platelets: Thombocytosis

2

What is the term for too little red, white and platelets

Red: Anaemia
White: Leucopenia
Platelets: Thrombocytopenia

3

Where do the genetic changes in CML occur?

Pluripotent stem cell

4

What is the common genetic abnormality in CML?

Translocation between chromosomes 9 (ABL) and 22 (BCR) leading to an increase in the ABL tyrosine kinase which is important in signal transduction and cell growth

5

What are the clinical features of CML?

Fatigue, weight loss, night sweats, splenomegaly, anaemia

6

What is used for the diagnosis of CML?

Changes on peripheral blood and BM biopsy
BCR-ABL translocation (cytogenetis)

7

What are the three phases of CML?

Chronic
Accelerated
Blast

8

What is the treatment of CML?

Tyrosine kinase inhibitor - Imatinib

Reduces the progression to accelerated phase or blast phase however some patients will develop mutations that reduce the effectiveness - new generation tyrosine inhibitors being used

9

What is polycythaemia vera?

Primary polycythaemia where there is an increase in RBC production independent of EPO

10

What are the clinical features of Polycythaemia vera?

Increased risk of arterial and venous thrombosis
Microcirculatory disorders - headaches, cisual disturbances, dizziness, erythromelagia
Hypertension
Plethora
Splenomegaly

11

What is the genetic mutation of polycythaemia vera?

Gain of function in Janus 2 kinase (JAK-2) which is the gene that encodes the tyrosine kinase a downstream regulator of EPO making cells hypersensitive to EPO

12

In which disorders will you see JAK2 mutations?

Polycythaemia vera
Essential thrombocytopenia
Primary idiopathic myelofibrosis

13

What is the diagnosis of polycythaemia vera?

Serum EPO suppressed
Identification of JAK2 mutation
Bone marrow biopsy: panmyelosis

14

What is the treatment of polycythaemia vera?

Venesection: reduces the blood volume and brings down the hematocrit levels; in patients with polycythemia vera, this reduces the risk of blood clots

Low dose aspirin
JAK2 inhibitors being developed

15

What is essential thrombocythaemia?

Chronic myeloproliferative neoplasm affecting the megakaryocytic lineage

16

What is the diagnosis of thrombocythaemia?

Sustained platelet count >450
Bone marrow: proliferation of megakaryocytes (no increase in erythropoiesis or granulopoiesis)
Doesn't meet criteria for other myeloproliferative disease
JAK2 V617F nutation positive

17

What is the clinical presentation of thrombocythaemia?

Most aymptomatic but can show thrombosis or haemorrhage

18

What is the treatment of thrombocythaemia?

Hydroxyurea (affects all cell lines)
Anagrelide (megakaryocyte line - more side effects)
Low dose aspirin if high risk of vascular events

19

What is primary myelofibrosis?

proliferation of megakaryocytes and granulocytes in the bone marrow

In developed disease this is associated with reactive deposition of fibrosis connective tissue and extramedullary haematopoiesis

20

What are the clinical features of primary myelofibrosis?

30% asymptomatic - incidental splenomegaly or FBC abnormalaties
Can mimic essential thrombocytopenia
90% splenomegaly
50% hepatomegaly
Fatigue, dyspnoea, weight loss, night sweats, bleeding

21

What is the diagnosis of primary myelofibrosis?

Leukoerythroblastic on blood film
Bone marrow biopsy - proliferative, fibrotic phases
May have JAK2 or anothe rmutation

22

What is the clinical course of primary myelofibrosis?

As it progresses cytopenias develop
Usually become transfusion dependent
Ongoing splenic enlargement
3-7 year survival if diagnosed in fibrotic phase
5-30% transformation into AML

23

What is Nilotinib?

Tyrosine kinase inhibitor used for imatinib resistant CML

24

What is Ponatinib?

Kinase inhibitor targets at ABL-BCR used for CML and Ph+ ALL

Effective for CML resistant to imatinib

25

What is Ruxolitinib?

JAK 1 and 2 inhibitor for myelofibrosis