Revised cytogenetic features and impact of myeloid derived suppressor cells (MDSCs) in elderly patients affected by myeloproliferative neoplasm (MPNs)

Actual cytogenetic risk stratification in primary myelofibrosis (PMF) is two-tiered: ‘favorable’ and‘unfavorable’. Recent studies have suggested prognostic heterogeneity within the unfavorable risk category. In 1002 PMN patients, we performed stepwise analysis of impact on survival from individual and prognostically ordered cytogenetic abnormalities, leading to a revised three-tieredrisk model: ‘very high risk (VHR)’, ‘favorable’ and ‘unfavorable’. Median survivals for VHR(n=75), unfavorable (n=190) and favorable (n=737) risk categories were 1.2 (HR 3.8, 95% CI 2.9–4.9), 2.9 (HR 1.7, 95% CI 1.4–2.0) and 4.4 years and survival impact was independent of clinically derived prognostic systems, driver and ASXL1/SRSF2 mutations. The current study clarifies the prognostic hierarchy of genetic risk factors in PMF and provides a more refined three-tiered cytogenetic risk model. Although the recent advantage of risk classification of patients, the only curative treatment for PMF is the allotransplantation, that is proposed to select fit patients. A total comprensive pathogenetic aspects of MPNs remain unclear, and the inflammation phenomena related to MPNs developments have been much less studied. To underline the “inflammed” and immune derangement in this setting of patients, we identified in MPNs patients, myeloid-derived suppressor cells (MDSCs), that are specialized immunosuppressor able to control the functions of other immune cells, able to suppress a strong anti-leukemia immune response, thereby supporting tumor immune escape, and preventing excessive inflammatory responses.We recollected samples of 55 new MPNs cases and analysed the presence of MDSCs and their correlation to clinical and molecular features. We enrolled 12 PMF, 10 Polycytemia Vera (PV), and23 Essential Thrombocytemia (ET), 5 with unclassifiable MPN. We identify that MDSCs are higher in MPNs patients than in health controls. MDSC levels were not correlated with JAK2 status,white blood cells, Hb levels, platelet counts, splenomegaly.In order to identify early patients who can benefit from target therapies, further studies are needed on the role of MDSCs in myeloid diseases and on the dysregulation of the lymphocyte T system in these diseases.