Molecular correlates of anemia in primary myelofibrosis: a significant and independent association with U2AF1 mutations

Anemia is a cardinal manifestation of primary myelofibrosis (PMF) and constitutes a negative prognostic factor, being an independent risk factor for survival both in the international prognostic score system (IPSS) and dynamic IPSS (DIPSS)-plus. Anemia in myelofibrosis is also inversely correlated with patient-reported quality of life. Between 35 and 54% of patients with PMF are anemic at diagnosis with a hemoglobin level of o10 g/dl with the proportion increasing to 47–64% after about 1 year from the time of diagnosis. Pathogenesis of PMF-associated anemia is poorly understood and is multifactorial, involving hypersplenism, chronic low-grade hemolysis and ineffective hematopoiesis, the latter influenced by both abnormal expression of proinflammatory cytokines and other growth factors and, intrinsic erythroid cell defects. Current drugs, including JAK inhibitors, are suboptimal in the treatment of PMF-associated anemia and better information on its pathogenesis is critical for the development of more effective drugs. In the current study of JAK2/CALR/MPL-annotated patients with PMF, we examined the correlation between anemia with both driver and non-driver mutations, as well as cytogenetic abnormalities, in order to gain better insight into its pathogenesis. This study was approved by the institutional review board of Mayo Clinic (Rochester, MN, USA). Study patients were selected from our institutional database of myeloproliferative neoplasms based on the 2008 World Health Organization criteria diagnosis of PMF.