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Chapter 15 Myeloproliferative neoplasms / 201

The term myeloproliferative neoplasms (MPN) occurs (heterozygous or homozogous) in the marrow
describes a group of conditions arising from marrow and blood of almost all patients with PV and in
stem cells and characterized by clonal proliferation approximately 50% of those with ET and primary
of one or more haemopoietic components in the myelofibrosis, showing the common aetiology of

bone marrow and, in many cases, the liver and these three diseases (Fig. 15.2 ). The mutation occurs

spleen. The three major non - leukaemic disorders
included in this classifi cation are: Table 15.1 Myeloproliferative diseases and

other myeloid neoplasms associated with
1 Polycythaemia vera (PV);
point mutation or rearrangement of tyrosine
2 Essential thrombocythaemia (ET); and
kinase genes.

3 Primary myelofibrosis.
Mastocytosis is also discussed in this chapter; Tyrosine kinase gene
BCR - ABL1 positive chronic myeloid leukaemia in Disease mutated
Chapter 14 and the myelodysplastic syndromes and Chronic myeloid ABL1
mixed myelodysplastic/myeloproliferative diseases leukaemia
in Chapter 16 .

Polycythaemia vera JAK2 V617F; JAK2 exon12
The non - leukaemic myeloproliferative disorders

are closely related to each other and transitional Primary JAK2 V617F; MPL W151L/K
myelofi brosis
forms can occur with evolution from one entity into
another during the course of the disease (Fig. 15.1 ). Essential JAK2 V617F; MPL W151L/K

These diseases are associated with clonal abnormali- thrombocythaemia
ties involving genes that encode cytoplasmic or Mastocytosis KIT D816V
receptor tyrosine kinase (Table 15.1 ). A single
acquired mutation of the cytoplasmic tyrosine Myeloid neoplasm PDGFRA, PDGFRB, FGFR1
with eosinophilia
kinase Janus - associated kinase 2 (JAK2) (Val617Phe)
Bone marrow stem cell
Acquired
abnormality

Principal cellular Red cell Mega- Reactive
proliferation precursors karyocytes fibrosis
Mutated Mutated Mutated
JAK2 95% JAK2 50% JAK2 56%

Clinical Polycythaemia Essential Primary
entity (rubra) vera thrombocythaemia myelofibrosis
10–20%
30%

5% 10%
Acute myeloid
leukaemia

Figure 15.1 Relationship between the three myeloproliferative diseases. They may all arise by somatic 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. The three diseases, polycythaemia rubra vera, essential thrombocythaemia and primary
myelofi brosis, are characterized by JAK2 mutation in a varying proportion of cases (see text).