How does plasma multi-omics network reveal the pathological mechanisms of acute promyelocytic leukemia?

1. What are the current treatment status and challenges of acute promyelocytic leukemia?

Acute promyelocytic leukemia (APL) is a special type of acute myeloid leukemia, whose pathogenesis is closely related to the formation of PML/RARA fusion gene. Currently, the targeted treatment regimen combining all-trans retinoic acid with arsenic trioxide (ATRA/ATO) has achieved a cure rate of over 90%, making it a model for tumor-targeted therapy. However, despite the remarkable efficacy, the specific mechanisms by which APL cells influence disease occurrence and treatment response through the regulation of plasma microenvironment components remain unclear. Existing research has mainly focused on genomic and transcriptomic changes in leukemia cells themselves, with limited systematic analysis of plasma as a critical microenvironment, which hinders a comprehensive understanding of the pathophysiological processes of APL.

2. What are the characteristics of the multi-omics analysis method used in the study?

To systematically analyze the multi-dimensional features of APL plasma, the research team collected paired plasma samples from 169 APL patients at diagnosis and during hematological complete remission after treatment, along with 106 age- and gender-matched healthy controls. Using a multi-omics integration strategy, they measured 88 clinical laboratory indicators, 991 plasma proteins, and 443 plasma metabolites, constructing a three-layer data system encompassing clinical parameters, proteomics, and metabolomics.

The study employed Spearman correlation analysis and modular clustering algorithms to build cross-level association networks, aiming to elucidate the regulatory patterns of plasma components under different clinical states. This method can identify complex interaction relationships among plasma components and reveal systemic disorder features in disease states.

3. What characteristic changes exist in the plasma of APL patients at diagnosis?

Single-omics analysis revealed two types of significant features in APL plasma at diagnosis. At the protein level, compared to remission and healthy controls, 303 differentially expressed proteins were identified in diagnostic plasma. Among these, 88 proteins were upregulated, mainly enriched in PI3K-AKT and ERK signaling pathways, which are closely related to metabolic reprogramming and survival of leukemia stem cells. In contrast, 102 proteins that increased during remission were involved in interferon-γ response, oxidative stress, and intrinsic apoptotic signaling pathways.

Metabolomic analysis showed that amino acid levels were significantly elevated in diagnostic plasma, while nucleosides, nucleotide metabolites, and tricarboxylic acid cycle-related metabolites were markedly reduced. This finding suggests that APL cells have active proliferation demands and energy consumption characteristics, requiring the uptake of large amounts of precursor substances like amino acids to support rapid proliferation.

4. What patterns are revealed by plasma association network analysis?

Further association network analysis showed that diagnostic plasma networks exhibited highly dense connectivity, containing 973 nodes and 2,527 significant edges. In contrast, remission and healthy control networks were significantly sparser, indicating widespread systemic disorder of plasma components in APL pathological states.

Through community clustering analysis, the study identified 12 core functional modules. The top-ranked module, with clinical indicators such as white blood cell count and lactate dehydrogenase as hub nodes, was enriched with proteins related to granulocyte activation and neutrophil degranulation, as well as metabolites associated with purine and pyrimidine metabolism. This module directly reflects the high proliferative activity of APL cells.

5. How does the PML/RARA fusion protein affect the plasma microenvironment?

To investigate the direct impact of APL cells on plasma components, the research team correlated gene expression data from bone marrow cells with plasma proteomics, identifying 48 genes highly expressed in APL cells whose encoded proteins were elevated in plasma. These proteins were primarily involved in cellular immune responses. Further integration with chromatin immunoprecipitation sequencing data revealed 12 target genes directly regulated by PML/RARA, whose encoded proteins were abnormally elevated in diagnostic plasma, suggesting that PML/RARA may influence plasma protein secretion through transcriptional regulation.

At the metabolic level, the high expression of genes related to nucleotide and amino acid synthesis enzymes in APL cells was consistent with low levels of corresponding metabolites in plasma. This indicates that APL cells may actively uptake plasma metabolites to meet their rapid proliferation demands, thereby altering the metabolic composition of plasma.

6. What changes occur in the plasma microenvironment after treatment-induced remission?

Notably, although remission plasma approached healthy states, 162 differential metabolites and 364 differential proteins remained. Among these, interferon-γ signaling pathway-related proteins were significantly enriched, and most of these proteins were intracellular. This finding suggests that ATRA/ATO treatment-induced apoptosis or senescence of APL cells may release large amounts of intracellular components, thereby activating the immune system's antitumor functions, providing new clues for understanding post-treatment immune microenvironment remodeling.

7. What is the application value of PML recombinant rabbit monoclonal antibody in related research?

As a specific research tool for recognizing PML protein, PML recombinant rabbit monoclonal antibody holds significant value in APL-related studies. This antibody can be used for protein expression analysis, detecting changes in PML protein expression under different disease states via immunoblotting. In cellular localization studies, immunofluorescence techniques can observe the distribution characteristics of PML protein within the nucleus. Additionally, the antibody can be used for protein interaction studies, analyzing the interaction network between PML and other nuclear proteins.

In mechanistic research, PML recombinant rabbit monoclonal antibody helps explore the functions of PML/RARA fusion protein and its impact on downstream signaling pathways. It can also be used to develop new diagnostic methods, investigating the potential of PML protein as a disease marker, providing technical support for precise diagnosis and treatment monitoring of APL.

8. Which manufacturers provide PML recombinant rabbit monoclonal antibody?

Hangzhou Start Biotech Co., Ltd. has independently developed the "PML Recombinant Rabbit Monoclonal Antibody" (product name: PML Recombinant Rabbit mAb (S-1908-60), catalog number: S0B1457), a high-specificity, excellent sensitivity, and superior nuclear localization performance tool for detecting tumor suppressor proteins. This product was developed using recombinant rabbit monoclonal antibody technology and has been rigorously validated across multiple platforms, including immunohistochemistry (IHC), immunofluorescence (IF), and Western blot (WB). It plays a critical role in acute promyelocytic leukemia (APL) diagnosis, nuclear body function research, and antiviral immunity.

Professional Technical Support: We provide detailed product technical documentation, including interpretation standards for APL diagnosis, cell staining protocols, subtype identification information, and specialized technical consultation, fully assisting customers in obtaining accurate and reliable results in hematological tumor and cell biology research.

Hangzhou Start Biotech Co., Ltd. is committed to providing high-quality, high-value biological reagents and solutions for global innovative pharmaceutical companies and research institutions. For more information about the "PML Recombinant Rabbit Monoclonal Antibody" (catalog number S0B1457) or to request sample testing, please contact us.

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