DEPDC1B enhances malignant phenotypes of multiple myeloma through upregulating CCNB1 and inhibiting p53 signaling pathway.

The identification and investigation of key molecules involved in the pathogenesis of multiple myeloma (MM) hold paramount clinical significance. This study primarily focuses on elucidating the role of DEPDC1B within the context of MM. Our findings robustly affirm the abundant expression of DEPDC1B in MM tissues and cell lines. Notably, DEPDC1B depletion exerted inhibitory effects on MM cell proliferation and migration while concurrently facilitating apoptosis and G2 cell cycle arrest. These outcomes stand in stark contrast to the consequences of DEPDC1B overexpression. Furthermore, we identified CCNB1 as a putative downstream target, characterized by a co-expression pattern with DEPDC1B, mediating DEPDC1B's regulatory influence on MM. Additionally, our results suggest that DEPDC1B knockdown may activate the p53 pathway, thereby impeding MM progression. To corroborate these in vitro findings, we conducted in vivo experiments that further validate the regulatory role of DEPDC1B in MM and its interaction with CCNB1 and the p53 pathway. Collectively, our research underscores DEPDC1B as a potent promoter in the development of MM, representing a promising therapeutic target for MM treatment. This discovery bears significant implications for future investigations in this field.

Lumbar MR-based radiomics nomogram for detecting minimal residual disease in patients with multiple myeloma.

OBJECTIVES: Minimal residual disease (MRD) is a standard for assessing treatment response in multiple myeloma (MM). MRD negativity is considered to be the most powerful predictor of long-term good outcomes. This study aimed to develop and validate a radiomics nomogram based on magnetic resonance imaging (MRI) of the lumbar spine to detect MRD after MM treatment. METHODS: A total of 130 MM patients (55 MRD negative and 75 MRD positive) who had undergone MRD testing through next-generation flow cytometry were divided into a training set (n = 90) and a test set (n = 40). Radiomics features were extracted from lumbar spinal MRI (T1-weighted images and fat-suppressed T2-weighted images) by means of the minimum redundancy maximum relevance method and the least absolute shrinkage and selection operator algorithm. A radiomics signature model was constructed. A clinical model was established using demographic features. A radiomics nomogram incorporating the radiomics signature and independent clinical factor was developed using multivariate logistic regression analysis. RESULTS: Sixteen features were used to establish the radiomics signature. The radiomics nomogram included the radiomics signature and the independent clinical factor (free light chain ratio) and showed good performance in detecting the MRD status (area under the curve: 0.980 in the training set and 0.903 in the test set). CONCLUSIONS: The lumbar MRI-based radiomics nomogram showed good performance in detecting MRD status in MM patients after treatment, and it is helpful for clinical decision-making. KEY POINTS: • The presence or absence of minimal residual disease status has a strong predictive significance for the prognosis of patients with multiple myeloma. • A radiomics nomogram based on lumbar MRI is a potential and reliable tool for evaluating minimal residual disease status in MM.

Disseminated fusarium infection after allogeneic hematopoietic stem cell transplantation after CART: A case report.

BACKGROUND: Fusarium is a conditional pathogen that can cause invasive infection in patients with hematological diseases under immune function. METHODS: A case of recurrent and refractory Philadelphia chromosome-positive acute lymphoblastic leukemia was treated with allogeneic hematopoietic stem cell transplantation after chimeric antigen receptor-modified T cells treatment. RESULTS: During transplantation, disseminated Fusarium infection occurred, involving the skin, liver, spleen and central nervous system, and the patient eventually died. CONCLUSIONS: Early identification of Fusarium infection based on the characteristic rash and timely antifungal treatment can improve the cure rate.

Spinal MRI-Based Radiomics Analysis to Predict Treatment Response in Multiple Myeloma.

OBJECTIVE: The aim of this study was to explore the clinical utility of spinal magnetic resonance imaging-based radiomics to predict treatment response (TR) in patients with multiple myeloma (MM). METHODS: A total of 123 MM patients (85 in the training cohort and 38 in the test cohort) with complete response (CR) (n = 40) or non-CR (n = 83) were retrospectively enrolled in the study. Key feature selection and data dimension reduction were performed using the least absolute shrinkage and selection operator regression. A nomogram was built by combining radiomic signatures and independent clinical risk factors. The prediction performance of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis. Treatment response was assessed by determining the serum and urinary levels of M-proteins, serum-free light chain ratio, and the percentage of bone marrow plasma cells. RESULTS: Thirteen features were selected to build a radiomic signature. The International Staging System (ISS) stage was selected as an independent clinical factor. The radiomic signature and nomogram showed better calibration and higher discriminatory capacity (AUC of 0.929 and 0.917 for the radiomics and nomogram in the training cohort, respectively, and 0.862 and 0.874 for the radiomics and nomogram in the test cohort, respectively) than the clinical model (AUC of 0.661 and 0.674 in the training and test cohort, respectively). Decision curve analysis confirmed the clinical utility of the radiomics model. CONCLUSIONS: Nomograms incorporating a magnetic resonance imaging-based radiomic signature and ISS stage help predict the response to chemotherapy for MM and can be useful in clinical decision-making.

Primary breast double-hit lymphoma management and outcomes: a real-world multicentre experience.

BACKGROUND: Primary breast double-hit lymphoma (PB-DHL) is a rare, highly aggressive malignancy that poses challenges regarding accurate diagnosis and selecting optimal treatment regimens. METHODS: We retrospectively reviewed 48 cases of patients diagnosed with PB-DHL in six academic centres between June 2014 and June 2020 in China. Study-specific data were recorded, including treatment options, therapeutic evaluation, prognostic factors and relapse patterns, and the overall survival (OS) and progression-free survival (PFS) were evaluated. RESULTS: In total, 48 patients were enrolled, with 14 patients treated with DA-EPOCH-R/MA (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, alternating with high-dose methotrexate and cytarabine), 18 patients treated with DA-EPOCH-R (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and 16 patients treated with R-HyperCVAD (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate). The overall 5-year OS and PFS rates were 41.7% (95% confidence interval [CI], 27.6-56.8%) and 37.5% (95% CI, 24.0-52.6%), respectively. Of the three treatment regimens, the 5-year OS was higher in DA-EPOCH-R/MA group than in the DA-EPOCH-R or R-HyperCVAD subgroups (57.1% vs. 38.9% vs. 31.3%; P = 0.016), as was the 5-year PFS (50.0% vs. 38.9% vs. 25.0%; P = 0.035). Autologous stem cell transplantation (ASCT) prolonged the OS and PFS compared with non-ASCT patients (5-year OS: 72.2% vs. 23.3%; P < 0.001; 5-year PFS: 72.2% vs. 16.7 %, P < 0.001). Multivariate analysis identified tumour size, risk stratification, treatment with DA-EPOCH-R/MA, breast irradiation, and ASCT as significant prognostic factors. CONCLUSIONS: DA-EPOCH-R/MA is a promising regimen for PB-DHL, and breast irradiation yields complementary benefits for prognosis. ASCT significantly decreased disease relapse, providing a potential curative PB-DHL intervention and justifying ASCT as first-line therapy for young patients. More effective treatment strategies for PB-DHL patients remain encouraging.

[Effect of Polyvinyl Alcohol/Graphene Oxide Aerogel on the Biological Characteristics of Acute Leukemia Cell Lines].

OBJECTIVE: To investigate the effects of polyvinyl alcohol (PVA) + graphene oxide (GO, weight content 1 wt%) aerogel three-dimensional (3D) scaffolds culture system on the proliferation, phenotype and drug resistance of ALL cell line Jurkat and AML cell line HL-60. METHODS: Jurkat cells and HL-60 cells were seeded in PVA+GO aerogel scaffolds for culture, and the structure of cells were observed by the scanning electron microscopy. Cell proliferation activity was measured by Cell Counting Kit-8 (CCK-8), cell phenotypes were analyzed by flow cytometry after fluorescent staining, then were compared with 2D cultured cells. Ara-C was used in drug resistance experiment, and CCK8 was used to detected cell proliferation activity. RESULTS: The proliferation activity of Jurkat cells grown in aerogel scaffolds was higher than that by 2D cultured in long-term culture. However, in HL-60 cells, the proliferation activity on 3D scaffold only at the 8th to 20th day was higher than that on the traditional 2D culture. Expression of CD4 in Jurkat cells increased after culture for 30 days, but the cell phenotypes in the 3D aerogel scaffolds were similar to 2D cultured cells. Phenotype of HL-60 cells was certainly changed after culture for 30 days, the cells can be divided into CD13+CD14-CD45+HLA-DR+,CD13-CD14--CD45+HLA-DR+ and CD13-CD14-CD45+HLA-DR- groups, and a new CD13+CD14-CD45-HLA-DR+ group of cells appeared in the cells cultured in 3D scaffolds, but not in 2D cultured cells. Drug resistance experiments showed that Jurkat cells in aerogel scaffolds have stronger drug resistance than those in 2D culture. CONCLUSION: PVA+GO (1 wt%) aerogel scaffolds can improve the proliferation and drug resistance of leukemia cells, and the phenotypes were the same as those in 2D culture, which can be used for cell amplification and biology characteristics studies and drug experiments. However, cell phenotypes should be analyzed before culture, and the effects of phenotypes changes on drug resistance should be eliminated.

[Detection and clinical significance of JAK2 mutation in 412 patients with chronic myeloproliferative neoplasms].

OBJECTIVE: To investigate the frequency of JAK2V617F mutation in Chinese patients with chronic myeloproliferative neoplasms (MPN) and to study the relationship between JAK2V617F mutation and clinical characteristics. METHODS: JAK2V617F mutation was screened by allele-specific polymerase chain reaction (AS-PCR). RESULTS: JAK2V617F mutation was detected in 277 of the 412 patients with MPN. The frequency of JAK2V617F mutation was similar among essential thrombocythemia (ET), idiopathic myelofibrosis (IMF) and chronic myeloproliferative disorders-unclassified (MPD-U) (P > 0.05), but it was significantly lower than that in polycythemia vera (PV) (P < 0.05). The presence of JAK2V617F was found to be significantly correlative with advanced age at diagnosis (P < 0.01) and with higher hemoglobin levels and higher leukocyte counts (P < 0.05). Significant difference was found in complication of vascular events between JAK2V617 positive and negative patients (P < 0.05). JAK2V617F positive MPD-U patients were more prone to progress into typical MPN compared with JAK2V617F negative MPD-U patients. The association between abnormal karyotype and JAK2V617F was not found in cytogenetical analysis of 301 patients. CONCLUSION: The presence of JAK2V617F in MPD-U is associated with the disease development. There is a correlation between JAK2V617F mutation in MPN and advanced age, higher leukocyte counts, hemoglobin level and vascular events.

[Expression of JAK2V617F and MPLW515L/K mutation in 30 suspected cases of early myeloproliferative disorders].

OBJECTIVE: To investigate the prevalence of JAK2V617F and MPLW515L/K mutation in patients with slightly elevated platelets (BPC) or hemoglobin (Hb) not meeting the criteria of polycythemia vera (PV) or essential thrombocythemia (ET). METHODS: Genomic DNA from bone marrow or blood mononuclear cells was screened with allele specific polymerase chain reaction (AS-PCR) for JAK2V617F and MPLW515L/K mutation. The history of thrombosis was assessed retrospectively by patients files. RESULTS: Of 30 patients, 14 (46.7%) were positive for the JAK2V617F mutation, none of them had the MPLW515L/ K. Five of these 14 patients had a history of thrombosis. Follow-up results were available in 22 patients. Among them, 12 patients with JAK2V617F mutation turned out to be MPD in 6-24 months; only 2 out of 10 patients without this mutation evolved to MPD. CONCLUSION: JAK2V617F mutation could be one of the diagnosis criteria of early MPD. No MPLW515L/K expression was found in early MPD.

[The clinical implication of JAK2 mutation expression in patients with myeloproliferative disorders].

OBJECTIVE: To investigate the frequency and clinical implication of JAK2V617F mutation in Chinese patients with myeloproliferative disorders (MPD). METHODS: Genomic DNA from bone marrow or blood mononuclear cells of 137 cases of MPD was screened with allele-specific polymerase chain reaction (PCR) and JAK2V617F mutation was detected with gel electrophoresis. There were 57 cases with polycythemia vera (PV), 68 with essential thrombocythemia (ET), 12 with idiopathic myelofibrosis (IMF). RESULT: JAK2V617F mutation was detected in 42 (73.7%) of the 57 patients with PV, 40 (58.8%) of the 68 with ET and 8 (66.7%) of the 12 with IMF. Sequence analysis of PCR products from selected patients confirmed the coexistence of both mutant and wild-type alleles. A higher prevalence was observed in elderly patients with MPD (P < 0.05). Cytogenetic analysis was performed in 115 of the 137 patients. Among the 108 patients with normal karyotype, JAK2V617F mutation was detected in 74 patients (68.5%) as compared with 5 of the 7 patients with karyotypic abnormalities (71.4%). CONCLUSION: JAK2V617F mutation occurs in a significant percentage of Chinese patients with the myeloproliferative disorders. There is a higher prevalence in elderly patients.

Analysis of JAK2(V617F) mutation in Chinese patients with myeloproliferative disorders.

It is now well-recognized that the activating JAK2(V617F) mutation occurs in the majority of patients with polycythemia vera (PV) and approximately half of those with either essential thrombocythemia (ET) or myelofibrosis with myeloid metaplasia (MMM). Here we analyzed JAK2(V617F) mutation in 137 Chinese patients with myeloproliferative disorders by allele-specific polymerase chain reaction (PCR). DNA was extracted from methanol/acetic acid-fixed cells that had been routinely prepared for cytogenetic analysis. A single point mutation (Val617Phe) was identified in JAK2 in 42 (73.7%) of 57 patients with PV, 40 (58.8%) of 68 with ET, and eight (66.7%) of 12 with MMM.