Philadelphia chromosome-negative myeloproliferative
neoplasms include
primary myelofibrosis (PMF),
polycythemia vera (PV), and
essential thrombocythemia (ET). Although these 3 entities share many pathogenic characteristics, such as dysregulated
Janus kinase (JAK)/signal transducer and activator of transcription signaling, they differ substantially regarding prognosis, progression to
myelofibrosis (MF), risk of leukemic transformation, and specific medical needs. Accurate diagnosis and classification of myeloproliferative
neoplasms are prerequisites for appropriate risk-based
therapy and should be based on an integrated approach following the World Health Organization guidelines that, in addition to clinical, molecular, and cytogenetic evaluation, includes the examination of bone marrow morphology.
Reticulin fibrosis at presentation in ET and PV is associated with increased risk of myelofibrotic transformation, and higher
fibrosis grade in patients with MF is associated with worse prognosis. Additional assessment of
collagen deposition and
osteosclerosis may further increase diagnostic and prognostic precision. Moreover, the evaluation of bone marrow pathology has become very important in the new era of disease-modifying agents. In randomized controlled phase 3 studies, the JAK1/JAK2 inhibitor
ruxolitinib provided rapid and lasting improvement in MF-related
splenomegaly and symptom burden as well as a survival advantage compared with placebo or best available
therapy. Follow-up for up to 5 years of patients who participated in a phase 1/2 study of
ruxolitinib, revealed stabilization or reversal of
bone marrow fibrosis in a proportion of patients with MF. Combinations of
JAK inhibitors with other
therapies, including agents with antifibrotic and/or anti-inflammatory properties, may possibly decrease
bone marrow fibrosis further and favorably influence clinical outcomes.