ABSTRACT
CONTEXT.: In 2022, 2 distinct guidelines for the diagnosis of myeloid neoplasms became available: the 5th edition of the World Health Organization guideline (WHO2022) solely and the International Consensus Classification (ICC). Despite major overlap, there are important differences that can have important implications. OBJECTIVE.: To explore the current opinions and diagnostic practices of hemato-oncologists and hematopathologists across the United States. DESIGN.: An online anonymous survey was created using REDCap, and a secure link was shared via email to fellowship program leaderships and via posts on social media. RESULTS.: A total of 310 responses were obtained. Only 33 of 309 respondents (10.7%) reported using solely the 2016 World Health Organization guideline to make diagnoses, whereas 167 of 309 (54%) supplemented it with other guidelines. The rest were either not sure (17; 5.5%), used WHO2022 solely (46; 14.9%), or used ICC solely (6; 1.9%). The choice of guideline was not related to region (P = .15), practice setting (P = .86), or hospital size (P = .22). More than 90% reported it is a source of confusion in clinical diagnosis, management, trial design, and other areas. CONCLUSIONS.: Overall, our study found that having 2 distinct guidelines could be a source of confusion for physicians and calls for a unified diagnostic language.
ABSTRACT
Epithelial homeostasis and regeneration require a pool of quiescent cells. How the quiescent cells are established and maintained is poorly understood. Here, we report that Trpv6, a cation channel responsible for epithelial Ca2+ absorption, functions as a key regulator of cellular quiescence. Genetic deletion and pharmacological blockade of Trpv6 promoted zebrafish epithelial cells to exit from quiescence and re-enter the cell cycle. Reintroducing Trpv6, but not its channel dead mutant, restored the quiescent state. Ca2+ imaging showed that Trpv6 is constitutively open in vivo. Mechanistically, Trpv6-mediated Ca2+ influx maintained the quiescent state by suppressing insulin-like growth factor (IGF)-mediated Akt-Tor and Erk signaling. In zebrafish epithelia and human colon carcinoma cells, Trpv6/TRPV6 elevated intracellular Ca2+ levels and activated PP2A, which down-regulated IGF signaling and promoted the quiescent state. Our findings suggest that Trpv6 mediates constitutive Ca2+ influx into epithelial cells to continuously suppress growth factor signaling and maintain the quiescent state.
