Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts. Moreover, CLL-1 is expressed in leukemia stem cells (LSCs), but absent in hematopoietic stem cells (HSCs), which may provide a potential therapeutic target for AML treatment. We tested the expression of CLL-1 antigen on peripheral blood cells and bone marrow cells in healthy donor and AML patients. Then, we developed a chimeric antigen receptor (CAR) containing a CLL1-specific single-chain variable fragment, in combination with CD28, 4-1BB costimulatory domains, and CD3-ζ signaling domain. We further investigate the function of CLL-1 CAR-T cells. The CLL-1 CAR-T cells specifically lysed CLL-1+ cell lines as well as primary AML patient samples in vitro. Strong anti-leukemic activity was observed in vivo by using a xenograft model of disseminated AML. Importantly, CLL-1+ myeloid progenitor cells and mature myeloid cells were specifically eliminated by CLL-1 CAR-T cells, while normal HSCs were not targeted due to the lack of CLL-1 expression. CLL-1 CAR-T represents a promising immunotherapy for the treatment of AML.

The use of immune checkpoint inhibitors (ICIs) has been demonstrated in the treatment of numerous types of cancer and ICIs have remained a key focus of cancer research. However, improvements in survival rates only occur in a subset of patients, due to the complexity of drug resistance. Therefore, further investigations are required to identify predictive biomarkers that distinguish responders and non‑responders. Combined therapeutics involving ICIs and other modalities demonstrate potential in overcoming resistance to ICIs; however, further preclinical and clinical trials are required. Concurrently, prompt recognition and intervention of immune‑related adverse events are crucial to optimize the use of ICIs in clinical treatment. The present study aimed to review the current literature surrounding the mechanisms and application of ICIs, with the aim of providing a theoretical basis for clinicians.

Objective. AML is a heterogeneous disease both in genomic and proteomic backgrounds, and variable outcomes may appear in the same cytogenetic risk group. Therefore, it is still necessary to identify new antigens that contribute to diagnostic information and to refine the current risk stratification. Methods. The expression of C‐type lectin‐like molecule‐1 (CLL‐1) in AML blasts was examined in 52 patients with newly diagnosed or relapsed/refractory AML and was compared with two other classic markers CD33 and CD34 in AML, in order to assess the value of CLL‐1 as an independent biomarker or in combination with other markers for diagnosis in AML. Subsequently, the value of CLL‐1 as a biomarker for prognosis was assessed in this malignant tumor. Results. The results showed that CLL‐1 was expressed on the cell surface of the majority of AML blasts (78.8%) and also expressed on leukemic stem cells in varying degree but absent on normal hematopoietic stem cells. Notably, CLL‐1 was able to complement the classic markers CD33 or CD34. After dividing the cases into CLL‐1^high and CLL‐1^low groups according to cutoff 59.0%, we discovered that event‐free survival and overall survival (OS) of the CLL‐1^low group were significantly lower than that of the CLL‐1^high group, and low CLL‐1 expression seems to be independently associated with shorter OS. Conclusions. These preliminary observations identified CLL‐1 as a biomarker for diagnosis and prognosis of AML.

Emerging evidence suggested that mitophagy may play an important role in the progression of hepatocellular carcinoma (HCC), whereas the association between mitophagy-related genes and HCC patients’ prognosis remains unknown. In this study, we aimed to investigate the potential prognostic values of mitophagy-related genes (MRGs) on HCC patients at the genetic level. According to median immunoscore, we categorized HCC patients from TCGA cohort into two immune score groups, while 39 differential expression MRGs were identified. By using univariate analysis, we screened out 18 survival-associated MRGs, and then, the least absolute shrinkage and selection operator (LASSO) analysis was applied to construct a prognosis model that consisted of 9 MRGs (ATG7, ATG9A, BNIP3L, GABARAPL1, HTRA2, MAP1LC3B2, TFE3, TIGAR, and TOMM70). In our prognostic model, overall survival in the high and low-risk groups was significantly different , and the respective areas under the curve (AUC) of our prognostic model were 0.686 for 3-year survival in the TCGA cohort and 0.776 for 3-year survival in the ICGC cohort. Moreover, we identified the risk score as the independent factor for predicting the HCC patients’ prognosis by using single and multifactor analyses, and a nomogram was also constructed for future clinical application. Further functional analyses showed that the immune status between two risk groups was significantly different. Our findings may provide a novel mitophagy-related gene signature, and these will be better used for prognostic prediction in HCC, thus improving patient outcome.

Hematological malignancies account for over 1.3 million new cases and approximately 700,000 deaths annually. Despite advances in targeted therapies, immunotherapies, and antibody–drug conjugates, relapse, refractory disease, and acquired drug resistance remain critical challenges. Peptide–drug conjugates (PDCs) have emerged as a promising targeted delivery platform, combining peptide-mediated specificity with potent cytotoxic payloads. In this review, we summarized the fundamental design principles of PDCs, including targeting peptide selection, linker engineering, and payload optimization, with emphasis on the biological characteristics of hematological malignancies. We then examined current preclinical and clinical progress across multiple myeloma, acute myeloid leukemia, myelodysplastic syndromes, B-cell non-Hodgkin lymphoma, and chronic myeloid leukemia. We further discussed emerging strategies such as cathepsin B-responsive PROTAC-PDC hybrids, nanotechnology-assisted delivery, and artificial intelligence-guided molecular design. Finally, we addressed key translational challenges, including tumor heterogeneity, payload resistance, and pharmacokinetic constraints, and proposed future directions toward biomarker-driven precision PDC therapy for hematological malignancies.

A substantial proportion of patients are unsuitable candidates for the Dara-CyBorD regimen (daratumumab-cyclophosphamide-bortezomib-dexamethasone), the sta