Current murine models of myeloproliferative neoplasms (MPN) cannot address how MPN can invade hematopoietic organs from a defined single anatomical origin as observed in patients. Murakami et al. developed an immunocompetent wild-type mouse model of Polycythemia Vera (PV) spreading from a single bone marrow site. PV development was abrogated in mice with splenectomy or lacking carbonic anhydrase 1 (CA1) in mutant hematopoietic progenitors. Increased expression of CA1 was found in CD34+ cells from PV patients, and its pharmacologic inhibition decreased variant allele frequency in colony-forming assays, suggesting CA1 as a potential therapeutic target for PV.

See article, p. 285.

Approximately every fifth patient with myeloproliferative neoplasms (MPN) harbors a CALR mutation of either type I or type II, which differ in clinical features and outcomes. Ibarra et al. show that type I, but not type II, mutant CALR proteins lose Ca2+ binding, causing Ca2+ depletion from...

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