Annals of Hematology, Год журнала: 2024, Номер unknown
Опубликована: Дек. 7, 2024
Язык: Английский
Critical Reviews in Oncology/Hematology, Год журнала: 2024, Номер 201, С. 104424 - 104424
Опубликована: Июнь 23, 2024
The presence of FLT3 mutations, including the most common FLT3-ITD (internal tandem duplications) and FLT3-TKD (tyrosine kinase domain), is associated with an unfavorable prognosis in patients affected by acute myeloid leukemia (AML). In this setting, recent years, new inhibitors have demonstrated efficacy improving survival treatment response. Nevertheless, development primary secondary mechanisms resistance poses a significant obstacle to their efficacy. Understanding these crucial for developing novel therapeutic approaches overcome improve outcomes patients. context, use combination different targeted therapies been studied. This review provides update on molecular alterations involved inhibitors, describes how monitoring may be used guide strategy FLT3-mutated AML.
Язык: Английский
Процитировано
14
The Journal of Applied Laboratory Medicine, Год журнала: 2024, Номер 9(1), С. 76 - 91
Опубликована: Янв. 1, 2024
Abstract Background Comprehensive genomic profiling (CGP) with next-generation sequencing detects genetic alterations of hundreds genes simultaneously and multiple molecular biomarkers one test. In the personalized medicine era, CGP is increasingly used for cancer diagnosis, treatment selection, prognosis prediction. Content this review, we summarize benefits CGP, clinical utility challenges setting up in laboratories. Besides identified cancer-related genes, other such as tumor mutational burden, microsatellite instability, homologous recombination deficiency are critical initiating targeted therapy. Compared conventional tests, uses less specimen shortens turnaround time if need to be tested. RNA fusion assay liquid biopsy helpful additions DNA-based by detecting fusions/splicing variants complementing tissue-based findings, respectively. Summary Many previous hurdles implementing laboratories have been gradually alleviated decrease cost, availability both open-source commercial bioinformatics tools, improved reimbursement. These changes helped make available a greater population patients improving characterization their tumors expanding eligibility trials. Additionally, results on panels could further analyzed better understand biology various cancers identify new biomarkers.
Язык: Английский
Процитировано
10
PeerJ, Год журнала: 2025, Номер 13, С. e18661 - e18661
Опубликована: Янв. 7, 2025
Here, we have discussed the molecular mechanisms of p53-responsive microRNAs dysregulation in response to genotoxic stress diffuse large B-cell lymphoma (DLBCL) patients. The role micro ribonucleic acids (microRNAs) p53-signaling cellular has been studied. MicroRNAs are small non-coding RNAs, which regulate genes expression at post-transcriptional level. Many them play a crucial carcinogenesis and may act as oncogenes or suppressor tumor growth. understanding effect microRNA on oncogenesis achieved recent decades opens wide opportunities for diagnosis, prediction microRNA-based cancer therapy. Development new bioinformatics tools databases supports DLBCL research. We overview studies miRNAs regulating gene associated with tumorigenesis processes, particular emphasis their growth-suppressing factors. starting point is brief description classical biogenesis pathway p53 these molecules. analyze various leading this dysregulation, including mutations TP53 gene, DNA methylation, changes host-genes copy number, genes.
Язык: Английский
Процитировано
2
Seminars in Hematology, Год журнала: 2024, Номер 61(2), С. 83 - 90
Опубликована: Март 1, 2024
Chronic lymphocytic leukemia (CLL) is the most common type of in Western countries. CLL a highly heterogeneous disease: some patients may never require therapy and other relapse several times after different therapeutic strategies. Therefore, CLL, prognostic markers are essential to capture high-risk for clinical endpoints including early treatment requirement, progression BTK or BCL2 inhibitors Richter transformation. In stage biological biomarkers have been identified predict time requirement that could be used identify appropriate population intervention trial. However, at moment, standard care remains watch & wait since no survival benefit has trials with chemoimmunotherapy inhibitors. requiring TP53 disruptions who from long-term continuous BTKi. On opposite side spectrum, IGHV mutated devoid disruption fixed-duration venetoclax-obinutuzumab. between, heterogenous subgroup unmutated genes represents group which further efforts needed additional aimed selecting can long term BTKi therapy. context aggressive transformation namely syndrome, clonal relationship counterpart strongest biomarker. Clonally related syndrome still an unmet need requires new
Язык: Английский
Процитировано
8
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2438 - 2438
Опубликована: Март 9, 2025
Hematological malignancies comprise a wide range of relatively rare cancers with diverse spectrum biological and clinical presentations [...]
Язык: Английский
Процитировано
0
The Oncologist, Год журнала: 2025, Номер 30(3)
Опубликована: Март 1, 2025
Abstract Purposes Evidence has demonstrated that monitoring of the variable, diversity, and joining gene segments (VDJ) rearrangement immunoglobulin (Ig) in circulating tumor DNA (ctDNA) is highly valuable predicting prognosis patients with diffuse large B cell lymphoma (DLBCL). In this study, we investigated role both Ig heavy chain (IGH) kappa light (IGK) rearrangements detected ctDNA samples DLBCL progression. Methods Next-generation sequencing (NGS) was used to identify dominant V(D)J clonotypic tissue 33 patients. Minimal residual disease (MRD) monitored at interim end treatment, as well follow-up time by tracking (defined “NGS MRD” method) peripheral blood (PB) samples. The nomogram established predict 12-month 24-month progression-free survival (PFS) probability. Results Prior clones identified could be retrieved tissue-matched PB 26 (78.8%, 26/33) addition IGK IGH increased MRD detection rate from 42.9% 58.0% total series. NGS imaging scans showed poor concordance treatment (Kappa = 0.24) 0.28), fair 0.46). However, confirmed improved prognostic performance compared scans, served factors for PFS treatment. Notably, predicted relapse 3 prior scans. Furthermore, found faster clone clearance rates were associated favorable prognosis. model rates, together result important predictors progression DLBCL. Conclusions via a promising noninvasive tool prediction early
Язык: Английский
Процитировано
0
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(10), С. 4869 - 4869
Опубликована: Май 19, 2025
Liquid biopsy through the analysis of circulating tumor DNA (ctDNA) is emerging as a powerful and non-invasive tool complementing tissue in lymphoma management. Whilst remains diagnostic gold standard, it fails to detect molecular heterogeneity tumor’s multiple compartments poses challenges for sequential disease monitoring. In diffuse large-B-cell (DLBCL), ctDNA facilitates genotyping by identifying hallmark mutations (e.g., MYD88, CD79B, EZH2), enabling cluster classification. Dynamic changes levels during DLBCL treatment correlate strongly with progression-free survival overall survival, underscoring its value predictive prognostic biomarker. Hodgkin’s lymphoma, characterized scarcity malignant cells biopsies, provides reliable insights into biology, response therapy, relapse risk. primary central nervous system detection MYD88 L265P offers highly sensitive, specific, minimally invasive option. Likewise, aggressive T-cell lymphomas, supports profiling, aligns burden, shows high concordance tissue-based results. Ongoing future clinical trials will be critical validating standardizing applications, ultimately integrating liquid routine practice more personalized dynamic care.
Язык: Английский
Процитировано
0
Clinical and Experimental Medicine, Год журнала: 2024, Номер 24(1)
Опубликована: Апрель 5, 2024
Abstract Liquid biopsy is a minimally invasive diagnostic tool for identification of tumor-related mutations in circulating cell-free DNA (cfDNA). The aim this study was to investigate feasibility, sensitivity, and specificity non-invasive prenatal test (NIPT) chromosomal abnormalities cfDNA from total 77 consecutive patients with non-Hodgkin B-cell lymphomas, Hodgkin lymphoma (HL), or plasma cell dyscrasia. In case series, half had at least one alteration, more frequently chromosome 6 (23.1%), 9 (20.5%), chromosomes 3 18 (16.7%), losses gains 7 negatively impacting on overall survival (OS), 5-year OS 26.9% median 14.6 months, respectively ( P = 0.0009 0.0004). Moreover, lymphomas the highest NIPT positivity, especially those aggressive while dyscrasia extramedullary disease higher positivity compared conventional cytogenetics analysis worse outcome. Therefore, we proposed NIPT-based liquid complementary abnormality detection hematological malignancies. However, prospective studies larger cohorts are needed validate clinical utility routinely practice.
Язык: Английский
Процитировано
2
Genome Medicine, Год журнала: 2024, Номер 16(1)
Опубликована: Май 20, 2024
Abstract Background Rare oncogenic driver events, particularly affecting the expression or splicing of genes, are suspected to substantially contribute large heterogeneity hematologic malignancies. However, their identification remains challenging. Methods To address this issue, we generated largest dataset date matched whole genome sequencing and total RNA malignancies from 3760 patients spanning 24 disease entities. Taking advantage our size, focused on discovering rare regulatory aberrations. Therefore, called outliers using an extension workflow DROP (Detection Outliers Pipeline) AbSplice, a variant effect predictor that identifies genetic variants causing aberrant splicing. We next trained machine learning model integrating these results prioritize new candidate disease-specific genes. Results found median seven outlier two splice-affecting per sample. Each category showed significant enrichment for already well-characterized with odds ratios exceeding three among genes in more than five samples. On held-out data, integrative modeling significantly outperformed based solely genomic data revealed promising novel Remarkably, truncated form low density lipoprotein receptor LRP1B transcript be aberrantly overexpressed about half hairy cell leukemia (HCL-V) samples and, lesser extent, closely related B-cell neoplasms. This observation, which was confirmed independent cohort, suggests as marker HCL-V subclass yet unreported functional role within Conclusions Altogether, census malignancy entities companion computational constitute unique resources deepen understanding events cancers.
Язык: Английский
Процитировано
1
Journal of Pediatric Surgery, Год журнала: 2024, Номер 60(2), С. 161887 - 161887
Опубликована: Авг. 30, 2024
Язык: Английский
Процитировано
1