This document provides information on myeloproliferative neoplasms (MPNs), a group of bone marrow disorders characterized by the overproduction of blood cells. It describes the main MPNs - polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). PV causes excessive red blood cell production. ET results in unusually high platelet counts. PMF involves the replacement of healthy bone marrow with scar tissue. The document outlines diagnostic criteria and clinical features of each condition, caused by mutations that stimulate the abnormal proliferation of stem/progenitor cells. Transitional cases between MPNs can also occur, or transformation to acute leukemia.

1. MYELOPROLIFERATIVE
NEOPLASM

2. OBJECTIVE
Students should be able to:
• Outline defining features of polycthaemia vera, essential
thromobocythaemia and primary myelofibrosis

3. Introduction
• The term myeloproliferative neoplasms (MPNs) describes a group of
conditions arising from marrow stem cells and characterized by clonal
proliferation of one or more haemopoietic components in the bone
marrow and, in some cases, the liver and spleen.
• They are often called the myeloproliferative diseases (MPDs)
 All MPDs arise from precursors of the myeloid lineage in the
bone marrow

4. Introduction
 Though MPDs are serious, and may pose certain health risks,
people with these conditions often live for many years after
diagnosis. The prognosis largely depends on the type of
disorder.

5. TYPES/CLASSIFICATION OF
MYELOPROLIFERATIVE NEOPLASMS (MPNs)
MPNs are classified as:
• Polycythaemia Vera
• Essential thrombocythaemia
• Primary myelofibrosis
• Chronic myeloid leukaemia (already discussed under
leukaemias)
• Chronic neutrophilic leukaemia
• Chronic eosinophilic leukaemia, not underwise specified
• Mastocytosis

6. POLYCYTHAEMIA
• Polycythaemia is defined as an increase in the packed cell
volume (haematocrit) / haemoglobin concentration above the
upper limit of normal for the patient’s age and sex.
• Raised packed cell volume (HCT)
Male > 49%, Female > 48%
OR
• Hb- >16.5 g/dl in men, > 16g/dl in women

7. Classification of polycythaemia
Classified as:
• Absolute
• Primary proliferative polycythaemia (polycythaemia vera) [a
type of MPNs]
• Secondary polycythaemia
• Idiopathic erythrocytosis
• Apparent
• Plasma volume or red cell mass changes

8. POLYCYTHAEMIA VERA (PV)
• PV is also known as polycythaemia rubra vera or primary proliferative
polycythaemia
• Occurs when the bone marrow produces too many blood cells, especially red
blood cells.
• Hence, PV is a clonal stem cell disorder characterised by increased red cell
production
• The same abnormal stem cell give rise to granulocytes and platelet leading to
moderate increase granulocyte and platelet count in many patients.
• More than 95% of patients with polycythemia vera carry the blood mutation,
JAK2.

9. • Fatigue, general malaise
• Difficulty breathing
• Intense itching after bathing in warm water
• Purple spots or patches on the skin
• Nosebleeds, gum or stomach bleeding, or blood in the urine
• Burning pain in the skin, often with darkened blotchy areas
• Headache and problems with vision
• High blood pressure
• Blockage of blood vessels. This may cause heart
disease, stroke, or gangrene (tissue death) of the arms and legs.
PV: Signs and Symptoms

10. Laboratory features of PV
• Hb, PCV (HCT), and Red cell mass increased
• Increased neutrophils and platelets
• Normal NAP
• Plasma urate high
• Hypercellular bone marrow
• Low serum erythropoietin

11. ESSENTIAL THROMBOCYTHAEMIA
•Also known as Primary thrombocytosis/idiopathic thrombocytosis
•occurs when the bone marrow produces too many platelets, which
can cause blood to clot. Clots can block blood vessels leading to heart
attack or stroke.
Thus, Clonal myeloproliferative disease of megakaryocytic lineage
• Sustained thrombocytosis (Platelet count >400 x 109/L) for more than 6
months
• Increase megakaryocytes
• Thrombotic or/and haemorrhagic episodes

12. ESSENTIAL THROMBOCYTHAEMIA
• Majority of people show mutation in JAK2 and rest in mostly CALR
gene and rarely in MPL gene
• CLINICAL FEATURES
• Heart attack or stroke
• Headache
• Burning pain, redness, and swelling of the hands and feet
• Bruising
• Gastrointestinal bleeding or blood in the urine

13. PRIMARY/IDIOPATHIC MYELOFIBROSIS
• Occurs when the bone marrow produces too much collagen or fibrous
tissue. This reduces bone marrow's ability to produce blood cells.
• There is progressive reactive fibrosis of the bone marrow in association
with the development of haemopoiesis in the spleen and liver (myeloid
metaplasia).
• Clinical features
• Massive splenomegaly
• Fatigue, general malaise
• Difficulty breathing
• Anaemia
• Weight loss
• Fever and night sweats
• Abnormal bleeding
• Metabolic derangement

14. Laboratory features of myelofibrosis
• Low haemoglobin
• High WBC at presentation
• Later leucopenia and
thrombocytopenia
• Leucoerythroblastic blood film
• Tear drops red cells
• Bone marrow aspiration- Dry
tap due to fibrosis
• Trephine biopsy- fibrotic
hypercellular marrow
• Increase in NAP score

15. Diagnosis of MPNs
• Physical examination – for an enlarged spleen.
• FBC & peripheral blood film -- detect abnormal types or numbers of red
or white blood cells. They can also detect anaemia and leukaemia.
• Bone marrow biopsy -- sample of bone marrow may be taken after blood
tests. It can show the presence of abnormal types or numbers of red or
white blood cells and may detect certain types of anaemia and cancer in
the marrow. Trephine biopsy is taken for myelofibrosis
•Cytogenetic analysis – preparation of blood or bone marrow are viewed
under a microscope to look for changes in the chromosomes.

16. • Relationship between the
three myeloproliferative
diseases. They may all
arise by mutation in the
pluripotential stem and
progenitor cells.
• Many transitional cases
occur showing features
of two conditions and, in
other cases, the disease
transforms during its
course from one of these
diseases to another or to
acute myeloid leukaemia.