Polycythemia vera (PV) is a clonal hematopoietic stem cell (HSC) disorder resulting in overproduction of erythrocytes. While Interferon-a (IFN-a) has shown therapeutic efficacy in PV and other myeloproliferative neoplasms (MPN), its precise mechanism of action remains poorly understood. In this study, we identify natural killer (NK) cells as primary immune effectors responsive to IFN-a treatment in PV essential for disease control in vivo. Using a transgenic mouse model of PV, we demonstrate that IFN-a induces the expansion of CD27+ NK cells in the bone marrow. In patients with PV or ET undergoing IFN-a therapy, the frequency of CD56bright NK cells is increased and correlates with the molecular response. Depletion of NK cells abrogated the therapeutic effects of IFN-a. In vitro experiments demonstrate that NK cells preferentially killed Jak2VF mutant hematopoietic stem and progenitor cells (HSPCs) in a TNF-a dependent manner and independent of IFN-g or NKG2D. Notably, PV mice depleted of NK cells or lacking type-I interferon (IFN) receptor on NK cells showed accelerated disease progression in the absence of exogenous IFN-a. This suggests that direct sensing of basal levels of type-I IFNs by NK cells is essential for attenuating disease progression, emphasizing a critical role for NK cells in immune surveillance of MPN. These findings offer new insights into type-I IFN-mediated immune modulation in MPN and highlight the potential of NK cell activation to improve therapeutic outcomes.

Chimeric antigen receptor (CAR) efficacy depends on the presence of antigen. While antigen levels in leukemias can be measured in the blood or bone marrow, expression in solid tumors is often inferred from archival tissues or remains undetermined. Neuroblastoma (NB) is an aggressive pediatric solid tumor for which we have co-developed a CAR targeting glypican 2 (GPC2). Here, we developed a radiotheranostic platform comprising an antibody-based positron emission tomography (immunoPET) agent, [[89]Zr]Zr-DFO-mCT3 ([89]Zr-mCT3), for non-invasive detection of GPC2 and [[225]Ac]Ac-macropa-mCT3 ([225]Ac-mCT3) for alpha-particle therapy. In orthotopic NB models with variable GPC2 levels, immunoPET accurately detected tumors with positive versus low/negative GPC2 status, which correlated with in vivo response to CAR. As a therapeutic agent, [225]Ac-mCT3 induced tumor regression in a dose-dependent manner, with the maximal effect at 2.96 kBq (80 nCi). Because [225]Ac-mCT3 does not downregulate GPC2, we assessed GPC2-CAR therapy with [225]Ac-mCT3 (1.48 kBq [40 nCi]) and showed improved survival in mice with GPC2[med] but not GPC2[high] tumors. These findings establish [89]Zr-mCT3 as a novel radiotracer for GPC2 monitoring and a predictive tool for CAR responses. [225]Ac-mCT3 enhances GPC2-CAR therapy in tumors with medium antigen levels, offering a rationale for the clinical development in NB and other pediatric tumors.

Tumors that develop in the bone exhibit poor responses to most treatment options, including advanced immunotherapies. Despite its immune-rich composition, the bone marrow microenvironment often fails to suppress tumor progression and instead promotes tumor growth and immune evasion, although the underlying mechanisms remain poorly understood. To investigate tumor-induced remodeling of the bone marrow immune environment and characterize tumor-infiltrating immune populations, we developed a high-dimensional 22-marker spectral flow cytometry panel for use in preclinical models of bone and bone marrow cancers. The panel enables profiling of major immune populations including CD4[+] T and CD8[+] T cells, B cells, Natural Killer cells, dendritic cells, monocytes, macrophages and neutrophils, and incorporates activation, exhaustion and immune checkpoint markers. Panel optimization was performed using spleen, freshly isolated bone marrow and tibial osteosarcoma tissue from adult BALB/c mice. While optimized for murine osteosarcoma and bone marrow tissue, this panel provides a robust and adaptable platform for high-dimensional immune profiling across solid tumors and hematological malignancies.

Purpose Radiolucent neoplasms can be identified on dental radiographs in asymptomatic and symptomatic individuals. Examples of these lesions include dentigerous cyst, radicular cyst, odontogenic keratocyst, and ameloblastoma. Many of these lesions require a histologic examination to render the definitive diagnosis. In terms of the ameloblastoma, there are four distinct types of this tumor. These include the conventional ameloblastoma, unicystic ameloblastoma (UA), extraosseous/peripheral ameloblastoma, and metastasizing ameloblastoma. The purpose of this report is to present a case report of a unicystic ameloblastoma found in a 30-year-old female who presented to a general dental practice with a chief complaint of pain and swelling in the mandibular left third molar region. Further evaluation and eventual surgical excision were delayed due to misdiagnosis and delay in performing the biopsy. The definitive diagnosis for this lesion was a benign unicystic ameloblastoma (UA). Due to the size of the defect, the patient required a partial mandibulectomy, reconstructive surgery and placement of two dental implants. While the long-term prognosis for this patient is good, regular surveillance is needed as UA neoplasms have a high recurrence rate. This case study emphasizes the need for oral health care professionals to be vigilant in identifying signs and symptoms of oral disease to support early and accurate diagnosis.

Mutations in calreticulin have been identified as driver mutations in BCR-ABL1-negative myeloproliferative neoplasms (MPNs) and are especially important for diagnostics and prognosis in primary myelofibrosis and essential thrombocythemia. The vast majority of pathogenic variants are insertions or deletions in exon 9 that result in a mutant C-terminal sequence that activates the signaling of the thrombopoietin receptor, which in turn promotes megakaryocytic proliferation. This review examines the potential clinical utility of calreticulin mutations as laboratory biomarkers in essential thrombocythemia (ET) and primary myelofibrosis (PMF). It emphasizes their role in confirming clonality in JAK2/MPL-unmutated cases, distinguishing a clonal myeloproliferative disease from reactive thrombocytosis, clarifying the molecular interpretation, and guiding molecular diagnostic workflows. Special focus is placed on practical laboratory challenges, such as choosing assays, detecting rare and non-canonical variants in exon 9, analytical sensitivity, molecular reporting, and the integration of bone marrow morphology, cytogenetics, co-mutations, and next-generation sequencing. Overall, clinical information gained from calreticulin testing is greatest when it is used in an integrated clinicopathologic and molecular testing context rather than as a standalone test. To make calreticulin mutations more effectively used for diagnosis or prognosis in routine hematology practice, we need standardization of testing, harmonization of reporting, and prospective validation of risk-models based on both the subtypes and the burden of the mutation.

Intraosseous hemangioma is a rare benign vascular tumor accounting for <1% of all bone tumors. This condition most commonly arises in the vertebrae and skull, while occurrence in the periorbital region is uncommon. We report 2 cases of intraosseous hemangioma arising in the nasal bone and zygomatic bone, respectively. Both patients were middle-aged females who presented with slowly progressive swelling. Computed tomography (CT) of Case 1 showed a characteristic sunray burst appearance, while Case 2 demonstrated a polka-dot sign. Both cases underwent complete surgical excision with a safety margin and reconstruction using autologous costal cartilage and cancellous iliac bone graft in nasal bone and zygomatic defects, respectively. Histopathologic examination confirmed cavernous hemangioma in both cases. No recurrence or significant complications were observed during follow-up. These findings suggest that surgical resection with appropriate reconstruction is an effective treatment for intraosseous hemangioma in the periorbital region.