Deregulation of apoptosis-related genes is associated with PRV1 overexpression and JAK2 V617F allele burden in Essential Thrombocythemia and Myelofibrosis

By real time PCR assay, we observed that A1, MCL1, BIK and BID, as well as A1, BCLW and BAK gene expression were increased in ET and PMF CD34+ cells respectively, while pro-apoptotic BAX and anti-apoptotic BCL2 mRNA levels were found to be lower in ET and PMF CD34+ cells respectively, in relation to controls. In patients' leukocytes, we detected an upregulation of anti-apoptotic genes A1, BCL2, BCL-XL and BCLW. In contrast, pro-apoptotic BID and BIMEL expression were downregulated in ET leukocytes. Increased BCL-XL protein expression in PMF leukocytes and decreased BID protein expression in ET leukocytes were observed by Western Blot. In ET leukocytes, we found a correlation between JAK2 V617F allele burden and BAX, BIK and BAD gene expression and between A1, BAX and BIK and PRV1 gene expression. A negative correlation between PRV1 gene expression and platelet count was observed, as well as a positive correlation between PRV1 gene expression and splenomegaly.Our results suggest the participation of intrinsic apoptosis pathway in the MPN physiopathology. In addition, PRV1 and JAK2 V617F allele burden were linked to deregulation of the apoptotic machinery.Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are disorders classified as Philadelphia chromosome-negative Myeloproliferative Neoplasms (MPN) [1]. ET is a clonal disease characterized by an increase in the platelet count associated with bone marrow megakaryocyte hyperplasia. Thrombosis and hemorrhagic events are the main co-morbities in ET patients. PMF is characterized by bone marrow fibrosis, as well as peripheral blood findings such as anemia, leukoerythroblastosis and the presence of dacryocytes in peripheral blood [2].The JAK2 V617F mutation, which leads to constitutive JAK2 activation, was shown to play an important role in MPN pathogenesis, and is found in 95% of Polycythemia Vera (PV) patients and in at least 50% of ET and PMF patients [3]. Constitutive JAK2 activation triggers several signal