Hailing Zhang

Primary myelofibrosis (PMF) is a Philadelphia chromosome (Ph)-negative myeloproliferative neoplasm (MPN) that features clonal proliferation of atypical megakaryocytes and myeloid cells, fibrosis of the bone marrow, extramedullary hematopoiesis, and increased risk of leukemic transformation to acute myeloid leukemia (AML). With the widespread application of molecular studies, especially next generation sequencing (NGS), significant advances have reshaped our understanding of the molecular pathogenesis of PMF and the prognostic relevance of specific gene mutations. In this review, we summarize its clinicopathologic features, genetic and molecular findings, updated diagnostic criteria, and differential diagnosis. These updates have been incorporated into the 5th edition of the World Health Organization classification of Hematolymphoid Tumors (WHO-5th) and the 2022 International Consensus Classification (ICC), thereby improving diagnostic accuracy and risk stratification, both of which are essential for tailoring treatment strategies and enhancing patient outcomes.

Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers characterized by the excessive production of blood cells in the bone marrow. These disorders arise from acquired genetic driver mutations, with or without underlying genetic predispositions, resulting in the uncontrolled production of red blood cells, white blood cells, or platelets. The excessive cell production and abnormal signaling from driver mutations cause chronic inflammation and a higher risk of blood clots and vascular complications. The primary goals of MPN treatment are to induce remission, improve quality of life and survival, as well as to reduce the risk of complications such as thrombosis, vascular events, and leukemic transformation. This review provides a comprehensive update on the diagnosis and therapeutic advancements in major MPN subtypes, including chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, and primary myelofibrosis. It examines these complex diseases from a molecular and evolutionary perspective, highlighting key clinical trials’ long-term follow-up and therapies targeting driver mutations that have transformed treatment strategies. Additionally, several important advancements in addressing challenges such as anemia in myelofibrosis, along with promising emerging therapies, are also discussed.

Mantle cell lymphoma (MCL) is a mature B‐cell lymphoma associated with cyclin D family rearrangements and typically expresses CD5 and cyclin D1. Epstein–Barr virus‐ (EBV‐) positive MCL is rare, and the role of EBV infection and its transformation in MCL remains unclear. We present a case of CD5‐negative classic MCL that progressed to an EBV + pleomorphic MCL six years after the initial diagnosis. Molecular studies confirmed the same clonal origin. To the best of our knowledge, the EBV‐positive transformation of CD5‐negative MCL into a pleomorphic variant has rarely been reported, and its recognition is important for the diagnosis and the management of patients with MCL.

Mast cell disorders range from benign proliferations to systemic diseases that cause anaphylaxis and other diverse symptoms to mast cell neoplasms with varied clinical outcomes. Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. The WHO 5th edition classification divides systemic mastocytosis into bone marrow mastocytosis, indolent systemic mastocytosis, smoldering systemic mastocytosis, aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia. The new ICC classifies SM slightly differently. The diagnosis of SM requires the integration of bone marrow morphologic, immunophenotypic, and molecular findings, as well as clinical signs and symptoms. Moreover, understanding the wide range of clinical presentations for patients with mast cell disorders is necessary for accurate and timely diagnosis. This review provides an updated overview of mast cell disorders, with a special emphasis on SM, including the latest approaches to diagnosis, prognostic stratification, and management of this rare disease.

Olfactory neuroblastoma is a rare disease with no randomized clinical trials to guide treatment decision making. Surgery, radiation, and chemotherapy are all used for treatment, and prognosis is mostly determined by the histologic grade and clinical stage. While a neuroendocrine type of neoplasm is similar to small cell carcinoma, metastatic disease in olfactory neuroblastoma is rare. We present a case at our institution of an uncommon clinical course of relapsed olfactory neuroblastoma complicated by severe thrombocytopenia.

Background: Tumor immunotherapy, a novel type of therapeutic treatment, has a wide range of applications with potentially prolonged benefits. However, current immunotherapy has a low overall response rate in treating a variety of tumors. Combination of immunotherapy with other therapies can improve the therapeutic response rates. The purpose of this work was to explore the potential of anti-angiogenic treatment in combination with tumor cell lysate loaded polydopamine nanoparticle vaccine as a therapeutic strategy for colon tumor. Methods: We grafted tumor cell lysate onto polydopamine nanoparticles as nano-vaccine (TCLN) and fabricated alginate hydrogel loaded with Endostar (EH), then detected characteristics of EH and TCLN. We also estimated the cytotoxicity of EH/TCLN in vitro. In the tumor-bearing mouse model, we evaluated the antitumor effect of EH/TCLN treatment, and developed the animal survival study. After performing the EH/TCLN treatment, we also analyzed T cells and DCs using flow cytometry, and determined T cell responses and tumor microenvironmental cytokines. At last, we assessed the effect of the EH/TCLN treatment on anti-angiogenesis further. Results: When applied in combination with TCLN in MC-38 tumor-bearing mice, EH/TCLN significantly suppressed tumor growth with more than half of the mice showing tumor regression. In addition, EH/TCLN treatment resulted in noticeable changes in the tumor microenvironment. As compared with the control group, EH/TCLN treatment led to significantly reduced tumor angiogenesis and expression of tumor microenvironment-related cytokines (TMCs), increased proportion of CD8⁺ T cells in the spleen, lymph node and tumor, elevated activity of cytotoxic T lymphocytes (CTLs) and tumor cell apoptosis. Conclusion: The present study demonstrated that the EH/TCLN treatment effectively created a favorable immune microenvironment for the induction of antitumor immunity and improved antitumor immune responses. Graphical Abstract:

Stimulus-responsive polymer materials have attracted much attention as drug carriers because of the ability to deliver drugs to the active site. Reactive oxygen species (ROS) play crucial roles in cellular signaling and regulation of oxygen homeostasis. However, ROS are present in abnormally high levels in many pathological environments. Based on the above points, three-arm poly(lactic-co-glycolic acid)-PO-poly(ethylene glycol) (3s-PLGA-PO-PEG or simply PP) was synthesized by using peroxalate esters (PO) as hydrogen peroxide-responsive linkages. PP was used to deliver promote hematopoietic recovery drugs erythropoietin (EPO) and EPO nanoparticles (EPO NPs) were prepared. We established a hematopoietic system injury model by ionizing radiation (IR) and unexpectedly found the good therapeutic effect of blank PP. Moreover, the administration of EPO NPs obviously decreased IR-induced ROS in bone marrow cells (BMCs) and reconstituted hematopoietic stem cells in BMCs. This study reveals a novel ROS-responsive polymer material that could be employed to remove excess ROS in the lesion and promote the efficacy of drug therapy.

We present the case of a 71-year-old male with an incidental diagnosis of seminoma coinciding with small lymphocytic lymphoma/chronic lymphocytic leukemia in the retroperitoneum. This case report illustrates the cytology, histology, immunohistochemistry, flow cytometry, and fluorescence in situ hybridization features of this exceptional case and sheds light on the importance of a collaborative multidisciplinary team in delivering quality patient care.

Polydopamine nanoparticles (PDA NPs) were prepared via dopamine self-polymerization; then, tumor cell lysate (TCL) was covalently attached onto the PDA NPs. The TCL loading capacity was 480 μg per mg of PDA NPs, and the resulting TCL@PDA NPs (241.9 nm) had perfect storage stability and negligible cytotoxicity against APCs. Tumor-bearing mice vaccinated with TCL@PDA NPs experienced significant delay in tumor progression due to the sufficient amount of CTLs and M1-type TAM as well as the deficient number of immunosuppression-related cells in the tumor tissues. Furthermore, empty PDA NPs had the ability to modulate DC maturation and delayed the development of tumors by facilitating the production of activated T cells and decreasing the subpopulation of MDSCs within the tumor microenvironment. Overall, these PDA NPs are expected to be a promising candidate for application as antigen delivery carriers because of their facile antigen loading method as well as their simple and rapid preparation process.