System Biology: An Emerging Toolkit for Improved Tyrosine Kinase Inhibition Therapy for Myeloproliferative Neoplasms

Abstract

an increased clonal proliferation of one or more myeloid lineages [1,2]. According to the World Health Organization (WHO), the classical myeloproliferative neoplasm can be divided into two major groups namely the Philadelphia chromosome positive group which includes chronic myeloid leukemia (CML) and the Philadelphia chromosome negative groups which includes Essential Thrombocythemia (ET), Polycythemia Vera (PV) and Primary Myelofibrosis (PMF) [3]. Due to an underlying clonal proliferation, patients with myeloproliferative neoplasms suffer complications including thrombosis and haemorrhage. Over time, patients develop progressive bone marrow failure and may also transform to acute myeloid leukemia. Studies identified three main mechanisms of pathophysiology which include (i) Somatic driver mutations that stimulate activation of various tyrosine kinase pathways, (ii) Cooperating driver mutations in myeloid genes and, (iii) Uncommon genetic factors that initiate different clinical neoplastic phenotypes [4]. Oncogenes in Myeloproliferative Neoplasms Underlying myeloproliferative neoplasms are abnormalities in various genes involved the tyrosine kinase signaling pathways [5]. These may include: