6rpx

Publication Abstract from PubMed

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.

CRLF3 plays a key role in the final stage of platelet genesis and is a potential therapeutic target for thrombocythemia.,Bennett C, Lawrence M, Guerrero JA, Stritt S, Waller AK, Yan Y, Mifsud RW, Ballester-Beltran J, Baig A, Mueller A, Mayer L, Warland J, Penkett CJ, Akbari P, Moreau T, Evans AL, Mookerjee S, Hoffman GJ, Saeb-Parsy K, Adams DJ, Couzens AL, Bender M, Erber WN, Nieswandt B, Read RJ, Ghevaert C Blood. 2022 Apr 7;139(14):2227-2239. doi: 10.1182/blood.2021013113. PMID:35051265^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.