Polycythemia, essential thrombocythemia, and myelofibrosis are three distinct myeloproliferative neoplasms (MPNs) that affect the bone marrow's production of blood cells. Here's a brief overview of each condition: 1. **Polycythemia (Polycythemia Vera):** - Polycythemia vera (PV) is a disorder where the bone marrow produces too many red blood cells, white blood cells, and platelets. This leads to an increased thickness of the blood (hyperviscosity), which can cause complications like blood clots, strokes, and heart attacks. - Symptoms may include fatigue, weakness, headaches, dizziness, itching (especially after a warm bath), and redness or a bluish tint to the skin. - Treatment aims to reduce the risk of blood clots and manage symptoms. It may include phlebotomy (removing blood to lower red cell count), medications to suppress bone marrow activity, and aspirin to reduce clotting. 2. **Essential Thrombocythemia (ET):** - Essential thrombocythemia is characterized by the overproduction of platelets in the bone marrow. This condition can lead to abnormal blood clotting or bleeding. - Symptoms may include headaches, dizziness, tingling or numbness in the hands or feet, vision changes, and easy bruising or bleeding. - Treatment focuses on reducing the risk of blood clots and managing symptoms. This may involve medications to lower platelet counts, such as hydroxyurea or anagrelide, as well as aspirin therapy. 3. **Myelofibrosis:** - Myelofibrosis is a condition where the bone marrow is replaced by fibrous tissue, leading to a decrease in the production of normal blood cells. It is often associated with anemia, enlarged spleen, and abnormal blood cell counts. - Symptoms may include fatigue, weakness, abdominal discomfort due to an enlarged spleen, easy bruising or bleeding, and frequent infections. - Treatment aims to manage symptoms and improve quality of life. This may involve medications to reduce spleen size and control symptoms, blood transfusions for anemia, and, in some cases, stem cell transplant for eligible patients. These conditions are chronic and require ongoing monitoring and management by healthcare professionals, often including hematologists or oncologists. Treatment plans are tailored to each individual based on factors such as age, overall health, disease progression, and risk of complications.

1. Myeloproliferative Neoplasms
(MPNs)

2. Objectives
• Definition of MPN
• Types of MPN
• Mutations of MPN
• Aetiology of MPN
• Clinical features of MPN
• CML and Philadelphia Chromosome
• Definition of each type

3. List of Contents:
• Definition
• Types
• PV
• ET
• MF
• CML and Philadelphia Chromosome
• Summary or conclusion
• Question

4. Myeloproliferative Neoplasms
MPNs (PV, ET, MF)
• Clonal hematopoeitic disorders
• Proliferation of one or more of myeloid lineages:
– Granulocytic
– Erythroid
– Megakaryocytic

5. Aetiology
Single acquired mutation of the cytoplasmic
tyrosine kinase Janus-associated kinase 2
(JAK2) (Val 617 Phe).
JAK2 mutation in:
All patients with Polycythemia Vera
and in 50% of those with Essential
Thrombocythemia and Idiopathic
Myelofibrosis

6. In MPN
• There are Relatively normal maturation of the cells
• Each type closely related to each other.
• Evolution from one entity into another occurs during
the course of the disease.
• Special risk of leukemic transformation

7. Activation of JAK2
Proliferation of cell
Receptor
Hemopoietic
growth factors
JAK2
Protein
Progenit
or cell
RBC Granulocyte
Megakaryocyte
Platelet
NORMALLY

8. Activation of JAK2
& Proliferation
of the cell
Without growth
factor
Receptor
Hemopoietic
growth factors
JAK2
Protein
MUTATION
Progenit
or cell
RBC Granulocyte
Megakaryocyte
Platelet
JAK2 Mutation

9. Bone marrow stem cell
Clonal abnormality
Granulocyte
precursors
Red cell
precursors
Megakaryocytes Reactive
fibrosis
Essential
thrombocytosis
(ET)
Polycythaemia
vera
(PV)
Myelofibrosis
AML
Chronic myeloid
leukemia
70%
10% 10%
30%

10. Polycythemia Vera
Definition of polycythemia
Its increase in the Hb concentration above the
upper limits of normal range for the patient age and
sex.
• Raised packed cell volume (PCV)
• Male > 52% (normally 40-52%)
• Female > 48% (normally 36-48%)
Classification
• Absolute(Total red cell volume & total plasma volume increased
» Polycythaemia vera
» Secondary polycythaemia
» Idiopathic erythrocytosis
• Apparent or relative

11. Polycythemia Vera
Polycythemia Vera is a clonal stem cell disorder
characterized by increased red cell production
• Abnormal clones behave autonomous
• Same abnormal stem cell give rise to granulocytes and
platelets

12. Clinical features
- The increased PCV leads to:
• an increased blood viscosity, Hyperviscosity
• abnormal platelet–endothelial contact increase thrombotic risk.
• Neurological features
Over and above the consequences of occlusive vascular lesions, the
sluggish cerebral blood flow secondary to the increased PCV is
thought to underlie features such as headaches, drowsiness,
insomnia, amnesia, tinnitus, vertigo, chorea and even depression.
• Transient visual disturbances also occur.

13. Polycythemia Vera
Laboratory features and morphology
• Hb, PCV (HCT), and Red cell mass increased
• Increased neutrophils and platelets
• NAP score normal or increased
• Serum uric acid high (gout)
• Circulating erythroid precursors (nucleated RBC)
• Hypercellular bone marrow
• Low serum erythropoietin

14. Secondary polycythemia
• Caused by compensatory erythropoietin ↑ in
- high altitudes
- pulmonary disease and alveolar hypoventilation
- cardiovascular disease.
- increased affinity Hb (familial polycythemia)
- heavy cigarette smoking.
• Caused by inappropriate erythropoietin increase in
- renal disease.
- tumours such as uterine fibroma, hepatocellular
carcinoma, cerebellar haemangioma.

15. Relative polycythemia
causes
• Stress or psudopolycythemia
• Cigarette smoking
• Dehydration : water deprivation, vomiting
• Plasma loss : burns.

16. Polycythemia Vera
Treatment
• To decrease PVC (HCT)
– Venesection
– Chemotherapy
• Treatment of complications

17. Essential Thrombocythemia (ET)
Primary thrombocytosis / idiopathic thrombocytosis
• Clonal myeloproliferative disease of megakaryocytic
lineage
• Sustained thrombocytosis >450 x 10 9/L & often >1000 x 10 9/L
• Increase megakaryocytes in the BM
• Thrombotic or/and hemorrhage episodes
• 2.5 cases/100,000
• M:F 2:1
• Median age at diagnosis: 60

18. Investigations
ET is a diagnosis of exclusion
• Rule out other causes of elevated platelet
count
• Infection
• Tissue damage (surgery)
• Chronic inflammation
• Malignancy

19. Blood film Bone marrow
increase platelet increase megakaryocyte
Essential Thrombocythemia
(ET)

20. Essential thrombocythemia
Primary thrombocytosis / idiopathic thrombocytosis
• Treatment
• Anticoagulant for thrombosis
• Chemotherapy to decrease platelet count
• Disease course and prognosis
• 25 % develops myelofibrosis
• Acute leukemia transformation
• Death due to cardiovascular complication

21. Myelofibrosis
Chronic idiopathic myelofibrosis
• Progressive fibrosis of the marrow & increase connective tissue
element
• Extramedullary erythropoiesis
– Spleen
– Liver
• Abnormal megakaryocytes which will stimulate fibroblasts &lead to
marrow fibrosis due to stimulation of platelet derived growth factor
& other protiens secreted by megakayocytes & platelets.
• 1/3 of patients have previous history of PV & some present with
clinical &lab features of both disorders.

22. Myelofibrosis
Investigations
• Anemia
• High WBC at presentation
• Later leucopenia and thrombocytopenia
• Leucoerythroblastic blood film
• Tear drops red cells
• Bone marrow aspiration- Failed due to fibrosis
• Trephine biopsy- fibrotic hypercellular marrow
• Increase in NAP score
• Transformation to acute myeloid leukaemia occurs
in 10-20% of patients
• High serum uric acid and LDH levels

23. Leukoerythroblastic blood picture Tear drop RBCs

24. Treatment
• Blood transfusions and regular folic acid
• Hydroxyurea
• Danazol
• Splenectomy
• The median survival is 3.5 years
• causes of death include heart failure, infection and leukemic
transformation.

25. Chronic Myeloid Leukemia
clonal disorder that results from a stem cell abnormality
marked proliferation of mature and maturing granulocytes.
• Most common adult leukemia
in Western world
• Slight Male predominance

26. • The disease accounts for around 15% of leukemia.
• Median age at presentation 50
• May occur at any age.
• Philadelphia Chromosome
t(9;22) is Positive in
more than 90%
• This translocation is
diagnostic of CML

27. What is Philadelphia Chromosome?
• Is the chromosome which result from the
t(9;22)(q34;q11)part of the Abelson proto-oncogene (ABL)
is moved from chromosome 9 to the (BCR) gene on
chromosome 22 & part of chromosome 22 moves to
chromosome 9.
• The abnormal chromosome 22 is
the Ph Chromosome code for
abnormal tyrosine kinase
Tyrosine Kinase leads to persistent
proliferation of the white cells
Philadelphia
Chromosome

28. Summary or Conclusion:
• MPNs:Clonal hematopoeitic disorders
• Proliferation of one or more of myeloid lineages:
– Granulocytic
– Erythroid
– Megakaryocytic
• Define chronic Myeloid leukemia
• Define Philadelphia chromosome

29. Questions?
• Define MPN
• Mention types of MPNs
• What are the diagnostic criteria for PV, ET and
MF?
• What are the investigations of each type
• THANK YOU