Myelofibrosis

Myelofibrosis (also known as primary myelofibrosis, agnogenic myeloid metaplasia, chronic idiopathic myelofibrosis, myelofibrosis with myeloid metaplasia, and idiopathic myelofibrosis) is a chronic myeloproliferative disorder characterised by (1,2):

• varying degrees of fibrosis of the bone marrow
• extramedullary haemopoiesis with splenomegaly
• anaemia with leukoerythroblastosis with teardrop poikilocytosis in peripheral blood (3)

The term “myelofibrosis” is being used to describe any increase in bone marrow stromal fibres (without considering the type of fibre or the associated disease) (4)

Marrow fibrosis is thought to occur as a result of increased secretion of platelet derived growth factor.

In myelofibrosis patients the disease initiating mutation is unknown. In a majority, a somatic Janus kinase 2 (JAK2) mutations (JAK2V617F) and in a minority MPL, LNK mutation is present (5)

• the discovery of mutations in JAK2, CALR, and MPL have uncovered activated JAK-STAT signaling as a primary driver of MF, supporting a rationale for JAK inhibition (6)

Loss of marrow capacity results in extramedullary haematopoiesis in the liver, spleen and lymph nodes.

Reference:

• (1) National Cancer Institute at the National Institutes of Health. Primary Myelofibrosis
• (2) Papageorgiou SG et al. Allogeneic stem cell transplantation as treatment for myelofibrosis. Bone Marrow Transplant. 2006;38(11):721-7
• (3) Cervantes F. Modern management of myelofibrosis. Br J Haematol. 2005;128(5):583-92.
• (4) Kuter DJ et al. Bone marrow fibrosis: pathophysiology and clinical significance of increased bone marrow stromal fibres. Br J Haematol. 2007;139(3):351-62.
• (5) Tefferi A. How I treat myelofibrosis. Blood. 2011;117(13):3494-504.
• (6) Schieber M, Crispino JD, Stein B. Myelofibrosis in 2019: moving beyond JAK2 inhibition. Blood Cancer J. 2019;9(9):74. Published 2019 Sep 11. doi:10.1038/s41408-019-0236-2