Molecular diagnosis of Non-Hodgkin’s lymphoma (NHL)

: Non-Hodgkin’s lymphoma(NHL) is the third most common hematologic malignancy in the world, and its various subtypes have distinct clinical manifestations, biological characteristics, and survival rates at different ages. Nearly ۵۵,۰۰۰ to ۶۰,۰۰۰ new cases of NHL are diagnosed annually in the United States. In pediatric NHL, which is aggressive and multicentric in origin, the first diagnosis occurs in the third or fourth stage. Currently used diagnostic pathways include morphologic and immunophenotypic studies, imaging scans, tissue biopsy, the elevation of absolute lymphocyte count and its ratio to monocytes, elevated lactate dehydrogenase(LDH) levels, low albumin levels, elevated aspartate transaminase(AST) levels, and several other factors evaluated through routine examinations. However, the need for more accurate, rapid, and efficient diagnostic methods has not been met, leading to further worldwide research. Therefore, we reviewed and summarized the novel molecular diagnostic approaches of NHL. Method: The terms “Molecular diagnosis” and “non-Hodgkin’s lymphoma” were searched in databases such as PubMed, Scopus, Google Scholar, Web of Science, etc., and relevant articles published since ۲۰۲۴ were selected and reviewed. Result: Assessment B-cell lymphoma ۲(Bcl-۲) and B-cell lymphoma ۶(Bcl-۶) are commonly used to diagnose B-NHL. Inappropriate lipid metabolism is one of the crucial aspects of cancer cells that can affect the progression of a tumor. Some studies have reported overexpression of apolipoprotein A-II (APOA۲) and YWHAZ in NHL. In another study, serum levels of S۱۰۰ calcium-binding protein A۸ (S۱۰۰A۸) and leucine alpha-۲-glycoprotein ۱(LRG۱) were significantly increased in the NHL group. S۱۰۰A۸ has also been shown to promote chemoresistance to adriamycin and vincristine by enhancing autophagy in B-cell lymphoma cells. A combination of S۱۰۰A۸ and LRG۱ has excess diagnostic value in screening NHL cases. Immunoglobulin gene sequencing could distinguish circulating tumor DNA (ctDNA) in diffuse large B-cell lymphoma(DLBCL) patients a few months before NHL diagnosis on positron emission tomography(PET)/computed tomography(CT) scan. ctDNA is useful not only for primary tumor profiling, but also for tracking tumor evolution, identifying resistance mutations, and finding residual disease after treatment. Investigation of B-cell clonality using immune gene hypermutation polymerase chain reaction (igHPCR) for molecular diagnosis of NHL is an effective way to access an accurate diagnosis. In one study, researchers found a positive association between sCD۲۷, sCD۳۰, and CXCL۱۳ circulators and DLBCL. S۱۰۰A۸/A۹ levels in saliva may help us to distinguish Sjögren's syndrome subtypes with lymphoma risk. Conclusion: NHL is a common hematologic malignancy with diverse subtypes at different ages. Recent findings have highlighted key molecular markers that may facilitate diagnostic accuracy and treatment monitoring. NHL progression is associated with elevated levels of APOA۲, YWHAZ, S۱۰۰A۸, and LRG۱. Genetic markers such as ctDNA from immunoglobulin gene sequencing may provide a non-invasive alternative to traditional imaging, allowing for early detection and real-time tumor tracking. Other prognostic factors include high levels of LDH, AST, lymphocytes, and monocytes, while low albumin levels are associated with increased treatment-related mortality. B-cell clonality assessment by IgH-PCR and circulating markers such as sCD۲۷, sCD۳۰, and CXCL۱۳ offer promising avenues for more accurate diagnosis and prognosis of NHL. However, more research is needed to find more accurate diagnostic methods.

کلیدواژه ها:

Non-Hodgkin’s lymphoma(NHL) ، molecular diagnosis ، circulating tumor DNA (ctDNA) ، B-cell lymphoma ۲ (Bcl-۲) ، B-cell lymphoma ۶ (Bcl-۶)