Myelofibrosis is most commonly caused by somatic mutations in the myeloproliferative leukemia virus (MPL) oncogene, the calreticulin (CALR) gene, or Janus kinase 2 (JAK2) gene. Less common mutations in other genes have also been documented. It can also be the result of other primary disorders manifesting as a complication or part of the disease process. Infections, malignancies, hematologic disorders, autoimmune diseases and exposure to certain toxins can also cause myelofibrosis.

There are no life-threatening causes of myelofibrosis, however complications resulting from untreated myelofibrosis is common.

Common causes of myelofibrosis include:

• Genetic mutations in:

• Myeloproliferative leukemia virus (MPL) oncogene^{[1][2][3][4][5][6][7][8][9][10][11]}
• Calreticulin (CALR) gene^{[1][2][3][4][5][6][7][8]}
• Janus kinase 2 (JAK2) gene^[9][10][11]

• Malignancies^{[12][13][14][15][16]}
• Hematologic disorders^{[16][17][18][19][20][21]}

• Infection^{[22][23][24][25]}
• Autoimmunity^{[26][27][28][29]}
• Toxins exposure^{[30][31][32][33][34][35][36][37]}
• Primary hyperparathyroidism^[38]

Common

Myelofibrosis is commonly caused by mutations in the following genes:

• Myeloproliferative leukemia virus (MPL) oncogene^{[1][2][3][4][5][6][7][8][9][10][11]}
• Calreticulin (CALR) gene^{[1][2][3][4][5][6][7][8]}
• Janus kinase 2 (JAK2) gene^[9][10][11]

Less Common

Myelofibrosis is less-commonly caused by mutations in the following genes:

• Additional sex combs-like 1 (ASXL1)^[39]
• Slicing factor, serine/arginine-rich 2 (SRSF2)^[39]
• Enhancer of zeste, drosophila, homolog 2 (EZH2)^[39]
• Neuroblastoma RAS viral oncogene homolog (NRAS)^[39]
• Kirsten rat sarcoma viral oncogene homolog (KRAS)^[39]
• Protein-tyrosine phosphatase, non-receptor type 11 (PTPN11)^[39]
• GATA-binding protein 2 (GATA2)^[39]
• Tumor protein p53 (TP53)^[39]
• Runt-related transcription factor 1 (RUNX1)^[39]

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