Gusheng Tang

Background: The presence of the RUNX1::RUNX1T1 fusion gene in patients diagnosed with acute myeloid leukemia (AML) subtype is often indicated by distinctive morphological features in myeloblasts from bone marrow (BM) smears. This study aims to evaluate the capacity of artificial intelligence (AI) to identify specific genetic abnormalities based solely on morphological characteristics. The intent is to investigate a non-invasive, cost-effective, and efficient preliminary screening method prior to the application of molecular biological assays. Methods: This multicenter trial included 205 patients diagnosed with AML, of which 75 were AML with RUNX1::RUNX1T1 fusion. A dataset of 65,039 myeloblasts images collected from the BM smears of these patients was compiled for model training, testing, and validation. The study also undertook a comparative analysis of the discrepancies between manual microscopy and AI-based identification. Results: The model demonstrated proficiency in adapting to varied clinical scenarios by applying two different threshold values. Under the threshold of 0.59, the testing and validation cohorts showed sensitivities of 92.86% and 95.65%, with corresponding accuracies of 87.04% and 71.88%. Conversely, by setting the threshold at 0.88, specificities of 92.31% and 92.68% were achieved, along with accuracies of 88.89% and 90.63%. Regardless of the threshold, the AI model consistently outperformed manual microscopy (average accuracy: 50.00%). Conclusion: The model demonstrates a significant capability to discern underlying RUNX1::RUNX1T1 genetic alterations from the morphological attributes of BM nucleated cells with a precision surpassing human observation. This providing a valuable tool highlights its potential for enhancing diagnostic efficiency in clinical practice.

Primary plasma cell leukemia (pPCL) is a rare and aggressive form of plasma cell disorder, which accounts for ~70% of all PCL. Survival of pPCL remains poor, and is related with early mortality. There is no standard therapy for patients with pPCL. In the present study, a 26‑year‑old man who was diagnosed with pPCL was reported. The patient achieved stringent complete remission to the successful treatment of intensive chemotherapy combined with sequential autologous and allogeneic stem cell transplantation (SCT) followed by maintenance therapy with oral administration of ixazomib, thalidomide and dexamethasone (IRD regimen). Development of complex treatment algorithms that combine novel agents, SCT and post‑transplantation remission strategies may translate into survival in patients with pPCL.

Nuclear respiratory factor‑1 (Nrf1) and mitochondrial transcription factor A (TFAM) are involved in the regulation of a variety of mitochondrial functional genes, which are associated with decreased sensitivity of tumor cells to chemotherapy. However, the expression status of Nrf1 and TFAM, as well as their clinical significance in breast cancer, is unknown. In the present study, tumor tissues and corresponding adjacent normal tissues were collected from 336 patients with breast cancer, and Nrf1 and TFAM expression was analyzed by immunohistochemistry using a tissue microarray. Expression of Nrf1 and TFAM was significantly increased in breast cancer tissue compared with adjacent normal tissues. In addition, patients positive for Nrf1 or TFAM had a poorer clinical prognosis than patients who were negative, and those positive for Nrf1 and TFAM had the shortest survival time. These results suggest that Nrf1 and TFAM are potential biomarkers for the determination of individualized therapy and the prognosis of breast cancer, and molecular targeting of Nrf1 and TFAM is a promising strategy for the sensitization of breast cancer cells to chemotherapeutics.

Acute myeloid leukemia (AML) is an aggressive clonal malignancy of hematopoietic progenitor cells with a poor clinical outcome. The resistance of leukemia cells to contemporary chemotherapy is one of the most formidable obstacles to treating AML. Combining valproic acid (VPA) with other anti-leukemic agents has previously been noted as a useful and necessary strategy which can be used to specifically induce anticancer gene expression. In the present study, we demonstrated the synergistic antileukemic activities between VPA and cytarabine (Ara‑C) in a retrovirus-mediated murine model with MLL-AF9 leukemia, three leukemia cell lines (THP-1, K562 and HL-60) and seven primary human AML samples. Using RT-qPCR, we noted that the combination of VPA and Ara‑C significantly upregulated Bax expression and led to the arrest of leukemia cell proliferation, sub-G1 DNA accumulation and cell apoptosis, as demonstrated by flow cytometric analysis. Significantly, further experiments revealed that knockdown of Bax expression prevented VPA and Ara‑C‑induced cell apoptosis in THP-1 cells. The results of our present study demonstrated the synergistic antileukemic effect of combined VPA and Ara‑C treatment in AML, and thus we suggest that VPA be used an alternative treatment for AML.

Hepatitis B surface antigen (HBsAg) and anti-HBs antibodies (anti-HBs) may coexist in certain chronic hepatitis B (CHB) patients. This study was designed to further explore the relationship between this coexistence and hepatitis B Virus (HBV) preS deletions. Sera of 28 patients carrying both HBsAg and anti-HBs (Group I) and those of another 28 HBsAg positive but anti-HBs negative patients (Group II) were collected from CHB patients. Direct sequencing of polymerase chain reaction products or sequencing of clones was applied to both groups to determine sequences of HBV preS and S genes. Genotyping of the S gene indicated that all sampled HBVs were either Genosubtype Ba or Genosubtype Ce. Seven samples in Group I harbored HBV preS deletion mutations. Three of the seven samples showed large deletion mutations in 3′ terminus of preS1 and co-existence of the mutant type and the full-length wild type, and the remaining four samples showed deletion mutations in 5′ terminus of preS2. All mutant strains were found to be genosubtype Ce. Only two samples in Group I showed G145R/A mutation. Only one sample in Group II contained preS deletion mutation. It is therefore concluded that HBV preS deletion mutations are likely to be related to the coexistence of HBsAg and anti-HBs in CHB patients (P-value = 0.024). Some immune reactions may select for the preS deletion in CHB patients with anti-HBs, the possible marker for immune selection. J. Med. Virol. 82:23–31, 2010.