Nwachukwu, Nneka

Abstract Introduction: The landscape of classical hematology has undergone substantial evolution over the last decade, marked by new diagnostic tools, nuanced therapeutic strategies, and an expanding understanding of underlying pathophysiology. This increasing complexity often presents unique diagnostic and therapeutic challenges. These challenges are further compounded by workforce shortages in classical hematology marked by educational gaps, geographic limitations, and difficulty accessing prompt specialty care. Unlike the well-established “Tumor Boards” in oncology, a comparable dedicated, widely accessible forum for classical hematology has largely been absent. This gap contributes to potential practice heterogeneity and isolation, especially across dissimilar care settings and geographic regions, impacting the consistent application of evidence-based practices and access to specialized expertise. To address this critical need, the “Blood Board” initiative was created to serve as an informal, virtual resource for discussing classical hematology topics and cases, fostering diverse perspectives, and collaborative problem-solving. Methods: The Blood Board was formally launched in April 2025, operating as a bi-monthly, hour-long virtual meeting conducted via non-recorded videoconferencing. The forum was designed with broad inclusivity in mind, welcoming all healthcare professionals involved in the care of adult patients with classical hematologic disorders, including trainees such as hematology/oncology fellows, academic and community-based hematologists, and any other interested providers. To date, dissemination of this initiative has been by word of mouth and e-mails containing a calendar invitation have been sent to anyone interested in participating (https://forms.gle/doyHNSx1SVFBJZmy8). To facilitate participation from various practice models and geographical locations, the virtual format was prioritized, eliminating barriers of travel and time commitment often associated with traditional in-person conferences. Participation is voluntary, encouraging an open and informal environment for de-identified case presentations, didactic discussions, and expert opinion sharing. Self-reported data on participant demographics (e.g., role, practice setting) and geographical representation have been collected to assess the initiative's reach and impact. Results: To date, sessions have consistently garnered engagement with a median of five participants in attendance at each session. There have been over 20 unique participants representing a broad spectrum of roles including both trainees and practicing hematologists/hematologist-oncologists and drawing from private practice, community-based hospitals, and academic medical centers. Over half of all participants were either in fellowship or within five years of completion of training. The virtual format has successfully overcome geographical limitations, attracting attendees from numerous states including Alabama, Florida, Georgia, Maryland, Minnesota, Missouri, Pennsylvania, South Dakota, and Wisconsin highlighting its broad appeal and potential for knowledge dissemination across a wide professional network. Conclusions: The Blood Board has demonstrated utility and met a previously unaddressed need. Sustained intellectual interest in Blood Board, coupled with a wide geographical and professional reach underscores a critical role for accessible, free, and multidisciplinary collaborative platforms in the evolving field of classical hematology. Similar to Tumor Boards, Blood Board promotes knowledge exchange and evidence-based care, garners expert support for challenging cases, and harmonizes clinical approaches, which we hope may ultimately improve patient care outcomes across diverse settings. Furthermore, this platform facilitates a national classical hematology community to support workforce development. Future goals include expanding dissemination efforts, measuring specific educational benefits, analyzing impacts on patient care, and increasing participant diversity, including recruitment of advanced practice providers and pharmacists.

Background While recent work from our laboratory showed that DNA (cytosine‐5)‐methyltransferase 3 beta (DNMT3b) is significantly increased in tissue from humans with calcific aortic valve stenosis and is associated with increases in global genomic methylation, it is unknown whether the net effects of these changes are protective or deleterious. The objective of this study was to test the hypothesis that genetic reduction of DNMT3b allows for increased anti‐osteogenic gene expression, and consequently results in suppression of osteogenic signaling and slower progression of valvular stenosis. Methods We used Ldlr −/− /ApoB 100/100 (LA) mice that were wild‐type for DNMT3b (LA‐DNMT3b +/+ ) or deficient in DNMT3b (LA‐DNMT3b +/− ) and fed a western diet for six months. Results Using quantitative real‐time RT‐PCR, we confirmed that expression of DNMT3b was reduced by ~50% in valves from haploinsufficient mice. In line with our hypothesis, reductions in DNMT3b were associated with increases in expression of FABP4 (which opposes osteogenesis) and Smad6 (which opposes canonical BMP signaling). Similarly, expression of the osteogenic genes Msx2 and Spp1 were substantially reduced in DNMT3b‐deficient mice. Critically, aortic valve cusp separation distance was significantly greater in DNMT3b‐deficient mice, demonstrating slower progression of valvular dysfunction. No other gross abnormalities were noted in the mice. Conclusions Collectively, these data suggest that selectively reducing DNMT3b activity may be a viable therapeutic approach to slowing progression of calcific aortic valve stenosis in humans. Support or Funding Information Grant Funding Source: Supported by NHLBI

Aging is a major risk factor for calcific aortic valve disease (CAVD). While recent work suggests that DNA methylation patterns are dramatically altered with aging, changes in DNA methylation patterns in age‐related cardiovascular diseases remain largely uncharacterized. Thus, we tested the working hypothesis that de novo DNA methyltransferase levels (DNMT3b in particular) are significantly increased in stenotic human aortic valves and would serve to repress expression of protective genes. We used human aortic valves that were either normal (NORM) or stenotic (STEN). qRT‐PCR and Western blotting were used to examine analyze changes in DNMT3b levels and markers of osteogenesis. DNA methylation was examined using ELISA‐based methods for total methylation and Illumina 450k Beadchip assays for site‐specific methylation between NORM and STEN valves. The pro‐osteogenic marker expression, Sp7, was increased by 4±1 fold in STEN valves compared to NORM tissue. While mRNA levels of DNMT3b only tended to be increased in STEN valves, protein levels of DNMT3b were dramatically increased in STEN valves compared to NORM valves (13.9±3‐fold increase). Increases in DNMT3b levels were associated with an increase in global DNA methylation, and 450k beadchip analysis identified more than 6,000 differentially‐methylated sites between NORM and STEN tissue. Collectively, these data identify DNA methylation as a potentially novel and major regulator of gene expression in end‐stage calcific aortic valve stenosis. NHLBI Grant Funding Source : NHLBI