Myelofibrosis is subclassified into primary and secondary types with the primary type being more common and a high proportion of the cases resulting from mutations in the Janus kinase 2 (JAK2) gene. It can be secondary to a variety of malignant, non-malignant, and hematologic conditions. It can also be secondary to malignancies, infections, toxins, autoimmune, and endocrine diseases.

• Myelofibrosis may be classified according to etiology into two types:

• Primary
• Secondary

• The primary type is associated with:^[1][2][3]
  • Stem cell-derived clonal myeloproliferation
  • Mutations of the Myeloproliferative leukemia virus (MPL) oncogene, the calreticulin (CALR) gene, or Janus kinase 2 (JAK2) gene in 90% of patients
  • “Triple-negative” in 10% of patients
• The 2016 World Health Organization (WHO) revised classification of myeloproliferative neoplasms (MPNs) defines 2 stages of primary myelofibrosis (PMF):

• Prefibrotic/early (pre-primary myelofibrosis) phase, characterized by granulocytic/megakaryocytic proliferation and lack of reticulin bone marrow fibrosis.^[4][5]
• Overtly fibrotic (overt primary myelofibrosis) phase, characterized by bone marrow fibrosis, pancytopenia, higher blast count, extramedullary hematopoiesis (EMH), and unfavorable karyotype with a significantly shortened median survival.^[4]

• Myelofibrosis can be secondary to toxins exposure and multiple primary conditions such as:

• Malignancies and hematologic disorders (Hodgkin lymphoma, non-Hodgkin lymphoma, essential thrombocythemia (ET), polycythemia vera (PV), multiple myeloma (MM), thrombotic thrombocytopenic purpura [TTP], and malignancies with metastases to the bone)^{[6][7][8][9][10][11][12][13][14][15][6][16]}
• Toxins (Benzene, thorium dioxide, nitrosourea, and x- or γ-radiation)^{[17][18][19][20][21][22][23][24]}
• Infections (tuberculosis [TB], HIV infection, and dengue fever)^{[25][26][27][28]}
• Autoimmune diseases (systemic lupus erythematosus [SLE], multiple sclerosis [MS], and juvenile idiopathic arthritis)^[29][30][31]
• Endocrine disorders (primary hyperparathyroidism)^[32]