Myeloproliferative Neoplasms with Monocytosis.

Abstract

Myeloproliferative neoplasms (MPN) are a heterogeneous group of hematopoietic stem cell neoplasms comprising of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) that share driver mutations (JAK2/CALR/MPL) resulting in constitutive activation of JAK/STAT and other signaling pathways. Patients with MPN have shortened survival and an inherent risk for leukemic evolution. Prognostically relevant clinical and genetic parameters have been incorporated into mutation-enhanced scoring systems (MIPSS70-plus version 2.0, MIPSS-ET/PV). In the current review, we describe clinical and pathological features along with prognostic significance of MPN with monocytosis. Monocytosis, defined by an absolute monocyte count (AMC) ≥ 1 × 10 9/L, is a typical manifestation of chronic myelomonocytic leukemia (CMML) but is also associated with 21% and 17% of PV and PMF patients, respectively. Recent studies on the subject have reported that MPN patients with monocytosis are older and present with concomitant leukocytosis. In regard to PV, patients with monocytosis harbor unfavorable cytogenetic abnormalities including +8, 7/7q, i(17q), 5/5q-,12p-, inv(3), or 11q23 rearrangement and SRSF2 mutations, whereas PMF patients with monocytosis had significant thrombocytopenia, higher circulating blasts, higher symptom burden, and ASXL1 mutations. Moreover, presence of monocytosis predicted inferior survival in both PV and PMF. Monocytosis in MPN is associated with a distinct clinical and genetic profile and may serve as a marker of aggressive disease biology.