Detecting bone marrow infiltration in nonosteolytic multiple myeloma through separation of hydroxyapatite via the two-material decomposition technique in spectral computed tomography.

Background: Conventional computed tomography (CT) has low sensitivity for the diagnosis of bone marrow infiltration in nonosteolytic multiple myeloma (NOL-MM). This study aimed to compare the performance of the two-material decomposition technique of spectral CT with the removal of X-ray absorption components of calcium (Ca) versus that of hydroxyapatite (HAP) for diagnosis of NOL-MM. Methods: From October 2022 to March 2023, a total of 41 consecutive patients with MM without focal bone lesions undergoing chest spectral CT and thoracic spine magnetic resonance imaging (MRI) in Fujian Medical University Union Hospital were prospectively enrolled; meanwhile, another set of 41 age- and sex-matched healthy consecutive participants were selected as a comparison group. Based on MRI findings, patients with MM were classified with a diffuse infiltration pattern MM (DP-MM) or a normal pattern MM (NP-MM). Regions of interest (ROIs) were manually drawn on vertebrae. CT values of 70-keV images and basic material density within the ROIs were stored. The basic two-material pairs included a Ca-related pair (Ca-X) and an HAP-related pair (HAP-X), with X referring to fat, water, or muscle. Material density values DCa(X), DX(Ca), DHAP(X), and DX(HAP) were each used to diagnose MM, and the area under the receiver operating characteristic curve (AUC) was used to assess diagnostic performance. Results: The 41 patients with NOL-MM included 30 with DP-MM and 11 with NP-MM. CT value, DCa(X), and DHAP(X) were comparable between the NOL-MM, DP-MM, NP-MM, and comparison groups. DX(HAP) was better than DX(Ca) for distinguishing the NOL-MM group from the comparison group {AUC [95% confidence interval (CI)], 0.874 (0.800, 0.949) vs. 0.737 (0.630, 0.844); P=0.02}, the DP-MM group from the comparison group [AUC (95% CI), 0.933 (0.878, 0.989) vs. 0.785 (0.677, 0.894); P=0.01], the NP-MM group from the comparison group [AUC (95% CI), 0.714 (0.540, 0.888) vs. 0.605 (0.429, 0.782); P=0.03], and the DP-MM group from the NP-MM group [AUC (95% CI), 0.809 (0.654, 0.964) vs. 0.736 (0.566, 0.907); P=0.049]. The diagnostic performance of DX(HAP) and DX(Ca) was influenced only by the removed material, while the X material had no influence. Conclusions: The spectral CT two-material decomposition technique with removal of X-ray absorption components of HAP is useful for diagnosis of NOL-MM, irrespective of the paired material.

SENP2 exerts an anti­tumor effect on chronic lymphocytic leukemia cells through the inhibition of the Notch and NF­κB signaling pathways.

Chronic lymphocytic leukemia (CLL) is one of the most often diagnosed hematological malignant tumors in the Western world and a type of inert B­cell lymphoma that commonly attacks the elderly. Small ubiquitin related modifier (SUMO)­specific protease 2 (SENP2) can act as a suppressor in various types of cancer by regulating the stability of ß­catenin to affect the Notch signaling pathway; however, it has a low expression level in CLL cells. In this study, we firstly used western blot analysis and RT­qPCR to detect the protein and mRNA expression levels of SENP2 in the peripheral blood of patients with CLL and healthy volunteers. Secondly, we overexpressed or knocked down the expression of SENP2 in CLL cells and then determined the cell invasive and chemotactic ability in a Transwell assay and chemotaxis assay. We examined the sensitivity of the cells to cytarabine and dexamethasone via a CCK­8 assay and determined the cell apoptotic condition and the expression of the Notch signaling pathway using flow cytometry and western blot analysis. The results demonstrated that the patients with CLL had relatively low expression levels of SENP2. The overexpression of SENP2 in the CLL cells decreased their invasive and proliferative ability, as well as their chemotactic response and enhanced their sensitivity to cytarabine and dexamethasone, while it promoted cell apoptosis. The silencing of SENP2 in the CLL cells generally produced the opposite results. We thus hypothesized that the overexpression of SENP2 downregulated ß­catenin expression, thus inhibiting the Notch signaling pathway in CLL cells. Moreover, the nuclear factor (NF)­κB signaling pathway was also regulated by the overexpression of SENP2. On the whole, the findings of this study indicate tha SENP2 can act as a tumor suppressor in CLL cells, and may thus prove to be a novel target for CLL treatment in clinical practice.