Sofia Gialesaki, Maurice Labuhn, Daniela Bräuer-Hartmann, Sören Matzk, et al.
Conclusion: Our Hsa21-wide CRIPSR-Cas9 screening in combination with functional validation in vitro and in vivo places a specific RUNX1 isoform in the center of an interaction network with mutated GATA1s during the transformation of fetal HSPCs in the background of trisomy 21. Our data highlight the importance of alternative splicing in leukemias and will guide the development of truly specific and targeted therapies.
Kirsten Fischer, Othman Al-Sawaf, Jasmin Bahlo, Anna-Maria Fink, et al.
Conclusion: Fixed-duration VenG induced deep, high (<10-4 in 3/4 of pts and <10-6 in 1/3 of pts), and long lasting MRD-negativity rates (with a low rate of conversion to MRD-positive status 1 year after treatment) in previously untreated pts with CLL and comorbidities, translating into improved PFS.
Mariateresa Pettinato, Mariam Aghajan, Maria Rosa Lidonnici, Violante Olivari, et al.
Conclusion: While Tfr2 haploinsufficiency does not impair systemic iron homeostasis, here we demonstrate that deletion of a single Tfr2 allele in the BM is sufficient to improve the hematological parameters of thalassemic mice. This finding paves the way toward a potential targeted therapy based on partial Tfr2 inhibition that might be beneficial for thalassemia (and potentially for other forms of anemia) without inducing defective hepcidin activation and iron overload. In addition, our results prove that targeting Tfr2 in combination with an anti-TMPRSS6 therapy may be a valuable therapeutic approach that strongly improves the thalassemic phenotype. However, Tmprss6 inhibition must be tightly controlled to avoid excessive iron restriction. Further experiments will allow setting up the optimal conditions.
Philippe Moreau, Michel Attal, Cyrille Hulin, Bertrand Arnulf, et al.
Conclusion: D-VTd in induction prior to and consolidation after ASCT improved depth of response (sCR, ≥CR, and MRD negativity) and PFS with acceptable safety. The favorable benefit-risk profile supports the use of D-VTd in transplant-eligible NDMM. CASSIOPEIA is the first study to demonstrate the clinical benefit of daratumumab plus standard of care in transplant-eligible NDMM patients.
Elliott Vichinsky, Carolyn C. Hoppe, Kenneth I. Ataga, Russell E. Ware, et al.
Conclusion: Voxelotor treatment demonstrated a dose-dependent increase in Hb, with the majority of patients on voxelotor 1500 mg achieving a >1.0-g/dL improvement in Hb from baseline to week 24. In addition, there was a dose-dependent decrease in measures of hemolysis with voxelotor. Furthermore, voxelotor was generally well tolerated. These results suggest that voxelotor has the potential to be disease-modifying by improving anemia and reducing hemolysis and their associated morbidity and mortality.
Christopher Hourigan, Laura Dillon, Brent Logan, Bart Scott, et al.
Conclusion: Detection of an AML-associated variant using ultra-deep next-generation DNA sequencing in the blood of AML patients in CR prior to alloHCT was associated with increased relapse rate and inferior overall survival in those randomized to RIC. This study provides evidence that intervention for AML patients with MRD can result in improved survival.