autologous Lung Spheroid Stem Cells / University of North Carolina-Chapel Hill, National Heart, Lung, and Blood Institute - LARVOL DELTA

Vaccination targeting azacytidine-induced neoantigens in the C1498 murine AML model (ASH 2025) - "Analysis of these predictedneoantigens identified 189 peptides with increased expression measured by TPM in AZA-treated cellscompared to controls, and 32 peptides with exclusive expression in AZA-treated cells. Neither Vaccine 1nor Vaccine 2 further prolonged survival when combined with AZA (median 31 days vs AZA + sham 31days). Vaccines alone did not improve survival compared to sham controls (median 19.5 vs 19 days).These findings indicate that, under current conditions, vaccination with neoantigens does not enhancethe therapeutic benefit of AZA, suggesting that further optimization of vaccine immunogenicity or antigenselection may be necessary."

IO biomarker • Preclinical • Tumor-specific neoantigens • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia

Norad long noncoding RNA, a decoy for pumilio RNA-binding proteins, elevates fetal hemoglobin levels (ASH 2025) - "For this, we firstoverexpressed NORAD lncRNA in HUDEP2 cells, and this led to a significant increase in gamma globinmRNA and protein levels, and hemoglobin HPLC documented up to 40% fetal hemoglobin (HbF) levelscompared to control cells that have less than 1% HbF...Lastly, we determined if NORAD lncRNA overexpression affects the progression of erythroid terminaldifferentiation. In both HUDEP2 cells and human HSPCs, the progress of erythroid terminaldifferentiation was not impeded upon NORAD lncRNA overexpression, similar to what we observed uponPUM1 knockdown.Taken together, our studies show that the overexpression of NORAD lncRNA, a decoy for Pumilio RNAbinding proteins, robustly increases fetal hemoglobin (HbF) levels without impeding erythroiddifferentiation, and therefore could serve as a novel approach to treat beta hemoglobinopathies such assickle cell anemia and beta thalassemia."

Anemia • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • NORAD • PUM1

Improved hematopoietic stem cell mobilization for gene therapy using single agent motixafortide in sickle cell disease (ASH 2025) - P1 | "Currently, HSC mobilizationfor SCD is limited to single agent plerixafor (P), a CXCR4 antagonist, since G-CSF is associated with anincreased risk of vaso-occlusive events (VOEs) and death...The median total number of CD34+ cellscollected/day with P was 2.6 x 106/kg compared to 6.8 x 106/kg with M. M was used first line in 3 patientswith preexisting clinical concerns precluding multiple collection cycles...To mitigate known local injection site and potential systemicreactions to M, all patients received prophylactic H-1 and H-2 antagonists and acetaminophen, with 82%receiving additional montelukast...Ongoing clinical trials of M in SCD are examining safety, mobilization efficacy,optimal dose timing, and editing potential (NCT06442761; NCT05618301). Additional studies arewarranted to determine the ideal prophylactic medication regimen."

Gene therapy • Dermatology • Gene Therapies • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Pruritus • Sickle Cell Disease • Urticaria • CD34

CD99 Promotes Self-renewal in Hematopoietic Stem Cells and Leukemia Stem Cells by Regulating Protein Synthesis. (PubMed, Blood) - "These data demonstrate a functional role for CD99 in constraining protein synthesis, which may promote the clonal expansion of HSCs and LSCs that leads to AML. Furthermore, these studies demonstrate that similar to HSCs, LSCs depend on maintenance of tightly regulated protein synthesis rates."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD99

Pre-emptive detection and evolution of relapse in acute myeloid leukemia by flow cytometric measurable residual disease surveillance. (PubMed, Leukemia) - "C-Flow-MRD-identified aberrancies in HLADRlow or CD34+CD38low (LSC-type) subpopulations contributed the greatest clinical accuracy (56% sensitivity, 90% specificity) and notably, by longitudinal profiling expanded rapidly within blasts in > 40% of 86 paired MRD and relapse samples. In conclusion, flow MRD surveillance can detect MRD relapse in high risk AML and its evaluation may be enhanced by computational analysis."

Journal • Residual disease • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD34 • FLT3