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Tumor cells can migrate from a primary cancer and form metastases by localizing to niches within other organs including the bone marrow, where tumor cells may exploit the hematopoietic stem cell niche. The precise composition of the premetastatic and the hematopoietic niches and the degree of overlap between them remain elusive. Because the extracellular matrix protein fibronectin is expressed in the pre-metastatic lung microenvironment, we evaluated the implications of its loss, as well as those of loss of its primary receptor subunit, β1 integrin, in various bone marrow cell types both in breast cancer bone metastasis and hematopoiesis. Using eight transgenic mouse models, we established that fibronectin production by osterix-expressing marrow cells, or β1 integrin expression (on vav, mx, or leptin receptor expressing cells), affects MDA-MB-231 breast cancer cell numbers in the bone marrow. Additionally, we identified stromal subpopulations that modulate transmigration through blood vessel walls. Not the number of tumor cells, but rather the changes in the microenvironment dictated whether the tumor progresses. Furthermore, hematopoiesis, particularly myelopoiesis, was affected in some of the models showing changes in tumor homing. In conclusion, there is partial overlap between the pre-metastatic and the hematopoietic niches in the bone marrow. Moreover, we have delineated a cascade starting with fibronectin secreted by pre-osteoblastic cells, which potentially acts on β1 integrin in specific stromal cell subsets, thereby inhibiting the formation of new breast cancer lesions in the bone marrow. This work therefore sheds light on the role of various stromal cell subpopulations that influence tumor behavior and affect hematopoiesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer of neuroendocrine origin that is typically associated with either the presence of Merkel cell polyomavirus or chronic exposure to ultraviolet (UV) light. We report a case of relapsed MCC that presented with new symptoms of fatigue, back pain, and myeloid left shift identified during scheduled follow-up. The patient was found to have circulating neoplastic cells in the peripheral blood and bone marrow metastasis. Immunohistochemistry for synaptophysin, CD56, INSM-1, CK20, CD117 were positive, whereas CD34, TdT, Chromogranin, CD10, myeloperoxidase, CD3 and CD19 were negative. Flow cytometry of the peripheral blood confirmed the presence of an abnormal nonhematopoietic cell population expressing CD56 positivity. A next-generation sequencing (NGS) panel revealed the presence of variants in RB1, TP53, and other genes, some of which have not been previously described in MCC. This rare presentation highlights the challenges in the diagnosis and management of MCC., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Extraneural metastasis of central nervous system tumors is generally rare and most often reported in glioblastomas and medulloblastomas, whereas oligodendrogliomas seem to have the lowest risk of extracranial metastasis. Given its infrequent occurrence, both the diagnosis and therapy of metastatic oligodendroglioma is often challenging., Case Presentation: This case study presents an oligodendroglioma, the isocitrate dehydrogenase 1 (IDH1) mutant, 1p/19q-codeleted tumor with bone marrow metastasis. The significance of this case lies in the comprehensive molecular analysis conducted for both the primary tumor and the metastasis. Chromosome 7 trisomy and chromosome 10 monosomy (+ 7/-10) were detected in the metastasis indicating molecular progression, which, to the best of our knowledge, has not been previously documented in metastatic oligodendroglioma., Conclusions: This case study serves additional information for better understanding of the metastatic capabilities of CNS tumors., (© 2024. The Author(s).)

Introduction: Neuroblastoma (NB) is the most common extra-cranial malignancy in children. Poor survival in high-risk NB is attributed to recurrent metastatic disease. To better study metastatic disease, we used a novel mouse model to investigate differential gene expression between primary tumor cells and metastatic cells. We hypothesized that metastatic NB cells have a different gene expression profile from primary tumor cells and cultured cells., Methods: Using three human NB cell lines (NGP, CHLA255, and SH-SY5Y), orthotopic xenografts were established in immunodeficient nod/scid gamma mice via subcapsular renal injection. Mice were sacrificed and NB cells were isolated from the primary tumor and from sites of metastasis (bone marrow, liver). RNA sequencing, gene set analysis, and pathway analysis were performed to identify differentially expressed genes and molecular pathways in the metastatic cells compared to primary tumor cells., Results: There were 266 differentially expressed genes in metastatic tumor cells (bone marrow and liver combined) compared to primary tumor cells. The top upregulated gene was KCNK1 and the top downregulated genes were PDE7B and NEBL. Top upregulated pathways in the metastatic cells were involved in ion transport, cell signaling, and cell proliferation. Top downregulated pathways were involved in DNA synthesis, transcription, and cellular metabolism., Conclusions: In metastatic NB cells, our study identified the upregulation of biologic processes involved in cell cycle regulation, cell proliferation, migration, and invasion. Ongoing studies aim to validate downstream translation of these genomic alterations, as well as target these pathways to more effectively suppress and inhibit recurrent metastatic disease in NB., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The exact prognostic role of cardiovascular (CV) risk factors in patients with BCR::ABL1 negative chronic myeloproliferative neoplasms (MPNs) remains unknown as it is often masked by other MPN-related features that bear strong prognostic impact on thrombotic risk. Therefore, current MPN treatment is not primarily guided by presence of CV risk factors. Treatment of CV risk factors in MPN patients usually mirrors that from the general population, despite the fact that CV risk factors in MPNs have their own specificities. Moreover, the optimal target levels for different metabolic deflections in MPNs (i.e., low-density lipoprotein, serum uric acid, or glycated hemoglobin levels) have not been defined. In the current review, we separately discuss the most important aspects of every individual CV risk factor (arterial hypertension, hyperlipidemia, chronic kidney disease, smoking, diabetes mellitus, hyperuricemia, and obesity and cachexia) in MPNs, summarize recent advances in the field, and propose future directions and research areas which may be needed to appropriately manage CV risk factors in MPNs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)