Skip to Main content Skip to Navigation
New interface
Journal articles

In Vivo Monitoring of Polycythemia Vera Development Reveals Carbonic Anhydrase 1 as a Potent Therapeutic Target

Abstract : Abstract Current murine models of myeloproliferative neoplasms (MPNs) cannot examine how MPNs progress from a single bone marrow source to the entire hematopoietic system. Thus, using transplantation of knock-in JAK2V617F hematopoietic cells into a single irradiated leg, we show development of polycythemia vera (PV) from a single anatomic site in immunocompetent mice. Barcode experiments reveal that grafted JAK2V617F stem/progenitor cells migrate from the irradiated leg to nonirradiated organs such as the contralateral leg and spleen, which is strictly required for development of PV. Mutant cells colonizing the nonirradiated leg efficiently induce PV in nonconditioned recipient mice and contain JAK2V617F hematopoietic stem/progenitor cells that express high levels of carbonic anhydrase 1 (CA1), a peculiar feature also found in CD34+ cells from patients with PV. Finally, genetic and pharmacologic inhibition of CA1 efficiently suppresses PV development and progression in mice and decreases PV patients’ erythroid progenitors, strengthening CA1 as a potent therapeutic target for PV. Significance: Follow-up of hematopoietic malignancies from their initiating anatomic site is crucial for understanding their development and discovering new therapeutic avenues. We developed such an approach, used it to characterize PV progression, and identified CA1 as a promising therapeutic target of PV. This article is highlighted in the In This Issue feature, p. 265
Complete list of metadata

https://hal-cnrs.archives-ouvertes.fr/hal-03800965
Contributor : DANIEL LEWANDOWSKI Connect in order to contact the contributor
Submitted on : Thursday, October 6, 2022 - 4:51:36 PM
Last modification on : Thursday, December 8, 2022 - 4:06:09 AM

Identifiers

Citation

Shohei Murakami, Vilma Barroca, Leïla Perié, Anne Bravard, Jacqueline Bernardino-Sgherri, et al.. In Vivo Monitoring of Polycythemia Vera Development Reveals Carbonic Anhydrase 1 as a Potent Therapeutic Target. Blood Cancer Discovery, 2022, 3 (4), pp.285-297. ⟨10.1158/2643-3230.BCD-21-0039⟩. ⟨hal-03800965⟩

Share

Metrics

Record views

13