Bone marrow renin-angiotensin system expression in polycythemia vera and essential thrombocythemia depends on JAK2 mutational status

Abstract

Recent observations raise possibility for constitutively active, mutated JAK2 to modulate expression of RAS genes in CMPD. We analyzed the expression of AGT, renin, AT2R1 and ACE genes in normal and bone marrows of PV and ET patients with the respect to the presence of V617F JAK2 mutation. PV and ET had different expression patterns of major RAS components compared to normal BM which was primarily associated with the JAK2V617F mutation and less with PV or ET disease phenotype. However, AT2R1 was exclusively markedly upregulated only in PV, while ET showed moderate expression irrespective of the JAK2 mutational status.

The effect of arterial hypertension on thrombosis in low‐risk polycythemia vera

“…Recent studies have shown that in the bone marrow of PV patients, the reninangiotensin system (RAS) is overexpressed and leads, in addition to hypertension, to bone marrow hematopoietic progenitor cell stimulation [5]. Moreover, there are observations that angiotensin-converting-enzyme (ACE) inhibitors reduce packed cell volume and hemoglobin concentration in polycythemia that follows renal transplantation [6].…”

“…LGLL have demonstrated that STAT3 mutations are present in 40% of cases [1]. STAT3 mutations have also been reported in hepatosplenic T cell lymphoma [2], anaplastic large cell lymphoma [3], extranodal NK/T cell lymphoma [4], and enteropathy-associated T cell lymphoma [5]. TET2 and DNMT3A mutations have been described in peripheral T cell lymphomas [6] but not in T-LGLL.…”

Local hematopoietic renin-angiotensin system in myeloid versus lymphoid hematological neoplastic disorders

“…3,4 The stimulation of the angiotensin type 1 and 2 receptors (AT1/AT2) by angiotensin II (Ang II), the principal effector molecule of the RAS, exerts an stimulatory/inhibitory action on the janus-kinase-signal transducer and activator of transcription (JAK-STAT) pathway, which is directly linked to activities of the erythropoietin, thrombopoietin and other hematopoietic cytokines during normal hematopoiesis and in myeloproliferative neoplasms. 3,5,6 Local RAS is effective even at the stage of primitive embryonic hematopoiesis. 7,8 There is preliminary evidence that local BM RAS could affect neoplastic hematopoiesis.…”

Local Bone Marrow Renin-Angiotensin System and Atherosclerosis

“…JAK1 and JAK2 inhibitor, INCB018424, decreased clonal neoplastic cells and downregulated inflammatory responses in MPD [101]. Since neoplasia and inflammation are the main pivotal actions of hematopoietic BM RAS, which is the upstream controlling pathway of JAK-STAT signaling [83, 102]; direct effects of INCB018424 on RAS shall be further searched to understand its clinically translated pleiotropic molecular engagements. The comparable biological actions of local RASs throughout the human body (including myocardium, pancreas, pituitary gland, ovary, and kidney) represent the true basis for the search of their prominence in tissue functions [83].…”