The present investigation focuses on the analysis of the interactions among human lactoferrin (LF), SARS-CoV-2 receptor-binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2) receptor in order to assess possible mutual interactions that could provide a molecular basis of the reported preventative effect of lactoferrin against CoV-2 infection. In particular, kinetic and thermodynamic parameters for the pairwise interactions among the three proteins were measured via two independent techniques, biolayer interferometry and latex nanoparticle-enhanced turbidimetry. The results obtained clearly indicate that LF is able to bind the ACE2 receptor ectodomain with significantly high affinity, whereas no binding to the RBD was observed up to the maximum “physiological” lactoferrin concentration range. Lactoferrin, above 1 µM concentration, thus appears to directly interfere with RBD–ACE2 binding, bringing about a measurable, up to 300-fold increase of the K_D value relative to RBD–ACE2 complex formation.

CAR-T therapy has transformed the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), particularly in pediatric and young adult patients. Many studies report one-year overall survival rates of between 60% and 80% following therapy. Event-free survival rates at one year are around 50–70%, with 40–50% of patients in remission after two years. Despite these impressive results, disease relapse remains a problem. Future CAR-T cell platforms should target multiple antigens, and the optimal design of such constructs must be determined. Modern trials should explore the role of CAR-T cell therapy as a consolidation treatment for patients with high-risk ALL, including those with persistent minimal residual disease at the end of induction/consolidation therapy, an IKZF1-positive gene expression profile, or a TP53 mutation or Ph-like gene expression profile. Improving the efficiency of gene-editing methods could lead to higher success rates in creating CAR-T cells, as well as reducing manufacturing time and costs. Producing universal CAR-T cells from healthy donors could significantly reduce production time and costs. These issues underscore the dynamic and evolving nature of B-ALL research. Ongoing studies and clinical trials are addressing many of these challenges in order to improve outcomes for B-ALL patients and expand the applications of CAR-T cell therapy.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a clinically challenging modality for the treatment of many hematologic diseases such as leukemia, lymphoma, and myeloma. Graft-versus-host disease (GVHD) is a common complication after allo-HSCT and remains a major cause of morbidity and mortality, limiting the success of a potentially curative transplant. Several microRNAs (miRNAs) have recently been shown to impact the biology of GVHD. They are molecular regulators involved in numerous processes during T-cell development, homeostasis, and activation, and contribute to the pathological function of T-cells during GvHD. Here, we review the key role of miRNAs contributing to the GvHD; their detection might be an interesting possibility in the early diagnosis and monitoring of disease

Background: Current drug therapy for myelofibrosis does not alter the natural course of the disease or prolong survival, and allogeneic stem cell transplantation is the only curative treatment modality. For over a decade, the Janus kinase (JAK) inhibitor ruxolitinib has been the standard of care. More recently, newer-generation JAK inhibitors have joined the ranks of accepted treatment options. Objectives: The primary goal of treatment is to reduce spleen size and minimize disease-related symptoms. Prognostic scoring systems are used to designate patients as being at lower or higher risk. For transplant-eligible patients, transplant is offered to those with a bridge of a JAK inhibitor; patients who are not eligible for transplant are usually offered long-term therapy with a JAK inhibitor. Limited disease-modifying activity, dose-limiting cytopenias, and other adverse effects have contributed to discontinuation of JAK inhibitor treatment. Conclusions: Novel JAK inhibitors and combination approaches are currently being explored to overcome these shortcomings. Further research will be essential to establish optimal therapeutic approaches in first-line and subsequent treatments.

Acute myeloid leukemia (AML) is an aggressive cancer with rapid progression and a high relapse rate, highlighting the urgent need for effective treatments. While recent advances in drug therapies and combination regimens have improved outcomes, relapsed and refractory (R/R) AML still shows low response rates, poor prognosis, and limited survival. The lack of effective immunotherapies further complicates the management of R/R AML. The bone marrow tumor microenvironment (TME) poses a significant barrier, requiring multifaceted, combined therapeutic strategies for clinical success. This TME creates an immunosuppressive and metabolically challenging environment that limits the expansion, persistence, cytotoxicity, and survival of chimeric antigen receptor (CAR) T cells. Unlike CD19 in B-cell acute lymphoblastic leukemia (B-ALL), AML lacks a truly leukemia-specific antigen. Although clinical trials are ongoing, no CAR-T therapies have received FDA approval for AML. This paper explores the reasons behind these ongoing challenges.