SLPI overexpression in hMSCs could be implicated in the HSC gene expression profile in AML.

Acute myeloid leukaemia (AML) is a severe haematological neoplasm that originates from the transformation of haematopoietic stem cells (HSCs) into leukaemic stem cells (LSCs). The bone marrow (BM) microenvironment, particularly that of mesenchymal stromal cells (hMSCs), plays a crucial role in the maintenance of HSCs. In this context, we explored whether alterations in the secretome of hMSCs derived from AML patients (hMSC-AML) could impact HSC gene expression. Proteomic analysis revealed that the secretome of coculture assays with hMSC-AMLs and HSC from healthy donor is altered, with increased levels of secretory leukocyte protease inhibitor (SLPI), a protein associated with important processes for maintenance of the haematopoietic niche that has already been described to be altered in several tumours. Increased SLPI expression was also observed in the BM plasma of AML patients. Transcriptome analysis of HSCs cocultured with hMSC-AML in comparison with HSCs cocultured with hMSC-HD revealed altered expression of SLPI target genes associated with the cell cycle, proliferation, and apoptosis. Important changes were identified, such as increased expression levels of CCNA2, CCNE2, CCND2, CD133 and CDK1 and decreased levels of CDKN2A and IGFBP3, among others. Overall, these findings suggest that the altered secretome of coculture assays with hMSC-AMLs and HSC from healthy donor, particularly increased SLPI expression, can contribute to gene expression changes in HSCs, potentially influencing important molecular mechanisms related to AML development and progression.

Primary diffuse large B-cell lymphoma of the head and neck in a Brazilian single-center study.

OBJECTIVES: Lymphomas represent around 10% of head and neck neoplasms, among which the diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype. In the present study, we characterized demographic parameters, anatomical sites, and survival rates of patients in a Brazilian cancer center. MATERIALS AND METHODS: Single-center retrospective epidemiological study of 243 head and neck DLBCL patients. Demographic characteristics, tumor localization, HIV status, lactate dehydrogenase (LDH) activity, and treatment modality were obtained from electronic medical records. RESULTS: The most common primary head and neck tumor location in patients with DLBCL was Waldeyer's ring. Interestingly, age above 80 years, male gender, high LDH levels, and HIV positivity were significantly associated with shorter overall survival (OS) rates and increased risk of death. We further demonstrated that treatment had a protective effect, improving OS, and reducing risk of death. Notably, we found no benefit of combination of chemotherapy and radiotherapy versus isolated treatment modalities. CONCLUSION: The study showed that primary head and neck DLBCL is more incident in middle age and elderly patients with a small male patients' majority in a Brazilian population. Moreover, we observed a 3-year OS rate of almost 60% and multivariate analysis showed that treatment was the only protective factor.