Overview of the Mutational Landscape in Primary Myelofibrosis and Advances in Novel Therapeutics

Document Type : Systematic Review and Meta-analysis


1 Ziauddin Hospital, Karachi, Pakistan.

2 Aga Khan University Hospital, Karachi, Pakistan.

3 Department of Internal Medicine, West Virginia University, Morgantown, WV, USA.

4 Department of Oncology, Aga Khan University Hospital, Karachi, Pakistan.

5 Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.


Primary Myelofibrosis is a BCR-ABL negative myeloproliferative neoplasm with a variety of hematological
presentations, including thrombosis, bleeding diathesis and marrow fibrosis. It is estimated to have an incidence of
1.5 per 100,000 people each year. Although JAK2 or MPL mutations are seen in PMF, several other mutations have
recently been documented, including mutations in CALR, epigenetic regulators like TET, ASXL1, and 13q deletions.
The identification of these mutations has improved the ability to develop novel treatment options. These include JAK
inhibitors like ruxolitinib, heat shock protein-90 inhibitors like ganetespib, histone deacetylase inhibitors including
panobinostat, pracinostat, vorinostat and givinostat, hypomethylating agents like decitabine, hedgehog inhibitors like
glasdegib, PI3K, AKT and mTOR inhibitors like everolimus as well as telomerase inhibitors like imtelstat. Research
on novel therapeutic options is being actively pursued in order to expand treatment options for primary myelofibrosis
however currently, there is no curative therapy other than allogenic hematopoietic stem cell transplantation (ASCT)
which is possible in select patients.


Main Subjects