Enalaprilat and losartan decrease erythroid precursors frequency in cells from patients with polycythemia vera.

Area of Science:

• Hematology
• Oncology
• Pharmacology

Background:

• Polycythemia Vera (PV) is a myeloproliferative neoplasm causing red blood cell overproduction.
• Current therapies focus on hematocrit reduction, with JAK2 inhibitors used for JAK2-mutated PV.
• Novel therapeutic strategies are needed to better understand and manage PV erythrocytosis.

Purpose of the Study:

• To investigate the potential of Angiotensin-converting enzyme (ACE) inhibition in controlling erythrocytosis in PV.
• To assess the effect of ACE inhibition on hematopoietic precursors in PV patients.

Main Methods:

• Mononuclear cells from PV patients (JAK2-positive and JAK2-negative) were isolated.
• Cells were treated with enalaprilat (ACE inhibitor) or losartan (AT1R antagonist).
• Clonogenic potential was assessed using colony-forming unit (CFU) assays.

Main Results:

• Enalaprilat and losartan treatment decreased erythroid precursor frequency in PV cells.
• This reduction was significant in JAK2-positive cells but occurred regardless of JAK2 mutation status.
• No significant effect was observed on other precursor types, and no dose-dependent effect was noted.

Conclusions:

• ACE inhibition effectively reduces erythroid precursor frequency in PV.
• ACE plays a role in PV erythrocytosis, independent of the JAK2 mutation.
• ACE inhibitors and AT1R antagonists show promise for directly managing PV erythrocytosis.