| First Author | Bennett C | Year | 2022 |
| Journal | Blood | Volume | 139 |
| Issue | 14 | Pages | 2227-2239 |
| PubMed ID | 35051265 | Mgi Jnum | J:334059 |
| Mgi Id | MGI:7294327 | Doi | 10.1182/blood.2021013113 |
| Citation | Bennett C, et al. (2022) CRLF3 plays a key role in the final stage of platelet genesis and is a potential therapeutic target for thrombocythemia. Blood 139(14):2227-2239 |
| abstractText | The process of platelet production has so far been understood to be a 2-stage process: megakaryocyte maturation from hematopoietic stem cells followed by proplatelet formation, with each phase regulating the peripheral blood platelet count. Proplatelet formation releases into the bloodstream beads-on-a-string preplatelets, which undergo fission into mature platelets. For the first time, we show that preplatelet maturation is a third, tightly regulated, critical process akin to cytokinesis that regulates platelet count. We show that deficiency in cytokine receptor-like factor 3 (CRLF3) in mice leads to an isolated and sustained 25% to 48% reduction in the platelet count without any effect on other blood cell lineages. We show that Crlf3-/- preplatelets have increased microtubule stability, possibly because of increased microtubule glutamylation via the interaction of CRLF3 with key members of the Hippo pathway. Using a mouse model of JAK2 V617F essential thrombocythemia, we show that a lack of CRLF3 leads to long-term lineage-specific normalization of the platelet count. We thereby postulate that targeting CRLF3 has therapeutic potential for treatment of thrombocythemia. |
