Gene mutations in chronic lymphocytic leukemia

Amin, Nisar A.; Malek, Sami N.

doi:10.1053/j.seminoncol.2016.02.002

Cited by 16 publications

(9 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…30 The negative impact of TP53 abnormalities is only partly mitigated, but not overcome, by ibrutinib, idelalisib, or venetoclax, at least in the relapsed/refractory setting. 6,44,46,47 A number of other gene mutations recurring at lower frequency have been signaled for their association with CLL outcome, including BIRC3, SAMHD1, RPS15, NFKBIE, EGR2, KRAS, and POT1. However, their annotation as CLL prognostic biomarkers is controversial or awaits validation studies.…”

Section: Genetic Lesionsmentioning

confidence: 99%

See 1 more Smart Citation

The mutational landscape of chronic lymphocytic leukemia and its impact on prognosis and treatment

2017

View full text Add to dashboard Cite

The typical genome of chronic lymphocytic leukemia (CLL) carries ∼2000 molecular lesions. Few mutations recur across patients at a frequency >5%, whereas a large number of biologically and clinically uncharacterized genes are mutated at lower frequency. Approximately 80% of CLL patients carry at least 1 of 4 common chromosomal alterations, namely deletion 13q14, deletion 11q22-23, deletion 17p12, and trisomy 12. Knowledge of the CLL genome has translated into the availability of molecular biomarkers for prognosis and treatment prediction. Prognostic biomarkers do not affect treatment choice, and can be integrated into prognostic scores that are based on both clinical and biological variables. Molecular predictive biomarkers affect treatment choice, and currently include TP53 disruption by mutation and/or deletion and IGHV mutation status. TP53 disruption by gene mutation and/or deletion associates with chemoimmunotherapy failure and mandates treatment with innovative drugs, including ibrutinib, idelalisib, or venetoclax. The mutation status of IGHV genes represents a predictive biomarker for identifying patients that may benefit the most from chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. Assessment of these biomarkers at the time of treatment requirement is recommended by most current guidelines for CLL management. Other molecular predictors are under investigation, but their application in clinical practice is premature.

show abstract

Section: Genetic Lesionsmentioning

confidence: 99%

“…However, their annotation as CLL prognostic biomarkers is controversial or awaits validation studies. 47…”

Section: Genetic Lesionsmentioning

confidence: 99%

The mutational landscape of chronic lymphocytic leukemia and its impact on prognosis and treatment

2017

View full text Add to dashboard Cite

show abstract

“…It was reported that del (13q) had a good prognosis compared to chromosome del (11q) which was reported in younger populations and more aggressive form of the disease . Furthermore, it was reported that in 40% of cases, the multidrug‐resistant gene was upregulated and contributed to chemotherapy resistance . It was found that BCL2 was upregulated in B‐CLL and was implicated in drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of long noncoding RNA Lnc‐IRF2‐3 and Lnc‐ZNF667‐AS1 is associated with poor survival in B‐chronic lymphocytic leukemia

El‐Khazragy

Esmaiel

Mohamed

et al. 2020

Int J Lab Hematology

View full text Add to dashboard Cite

Background Lnc‐IRF2‐3 and Lnc‐ZNF667‐AS1 were recently studied as a positive biomarker for many tumor cells. However, experimental studies found that they are associated with worse outcomes in B‐CLL. Methods A prospective case study was conducted on 135 B‐CLL patients that were compared to thirty healthy controls. The patients were followed up for 40 months and quantitative measurements of Lnc‐IRF2‐3 and Lnc‐ZNF667‐AS1 were measured and compared between the two groups as well as high‐risk and low low‐risk B‐CLL. Results Lnc‐IRF2‐3 and Lnc‐ZNF667‐AS1 had a high specificity (94% and 85%) and sensitivity (85%, 87%), respectively, to differentiate B‐CLL from healthy controls. Furthermore, they showed high expression levels in high‐risk CLL groups. For survival analysis, there was a negative correlation between overall survival (OS) and progression‐free survival (PFS) and both biomarkers. However, it was not evident in multivariate Cox regression analysis; in patients with Lnc‐IRF2‐3 expression level, >67 had a significant decrease in OS and PFS. However, there is no significant effect for high expression levels of Lnc‐ZNF667‐AS1 on OS (P = .16) or PFS (P = .48). Conclusion The Lnc‐IRF2‐3 and Lnc‐ZNF667‐AS1 are promising prognostic biomarkers in B‐CLL.

show abstract

“…Data processing was performed as described previously ( 13 , 29 ). The Proteome Discoverer (v1.3, Thermo Fisher) was used to integrate the search results of the SequestHT search engine (University of Washington) ( 30 ) against the human proteome (Swiss-Prot database, 20 279 reviewed protein sequences, September 27th 2013) accompanied with recurrent somatic CLL-associated mutations in 61 different proteins ( Supplementary Table 3 ) as described in the literature ( 31 , 32 ) and assigned in the COSMIC database ( ) ( 33 ) without enzymatic restriction. Precursor mass tolerance was set to 5 ppm.…”

Section: Methodsmentioning

confidence: 99%

Immunopeptidomics-Guided Warehouse Design for Peptide-Based Immunotherapy in Chronic Lymphocytic Leukemia

et al. 2021

View full text Add to dashboard Cite

Antigen-specific immunotherapies, in particular peptide vaccines, depend on the recognition of naturally presented antigens derived from mutated and unmutated gene products on human leukocyte antigens, and represent a promising low-side-effect concept for cancer treatment. So far, the broad application of peptide vaccines in cancer patients is hampered by challenges of time- and cost-intensive personalized vaccine design, and the lack of neoepitopes from tumor-specific mutations, especially in low-mutational burden malignancies. In this study, we developed an immunopeptidome-guided workflow for the design of tumor-associated off-the-shelf peptide warehouses for broadly applicable personalized therapeutics. Comparative mass spectrometry-based immunopeptidome analyses of primary chronic lymphocytic leukemia (CLL) samples, as representative example of low-mutational burden tumor entities, and a dataset of benign tissue samples enabled the identification of high-frequent non-mutated CLL-associated antigens. These antigens were further shown to be recognized by pre-existing and de novo induced T cells in CLL patients and healthy volunteers, and were evaluated as pre-manufactured warehouse for the construction of personalized multi-peptide vaccines in a first clinical trial for CLL (NCT04688385). This workflow for the design of peptide warehouses is easily transferable to other tumor entities and can provide the foundation for the development of broad personalized T cell-based immunotherapy approaches.

show abstract

Gene mutations in chronic lymphocytic leukemia

Cited by 16 publications

References 74 publications

The mutational landscape of chronic lymphocytic leukemia and its impact on prognosis and treatment

The mutational landscape of chronic lymphocytic leukemia and its impact on prognosis and treatment

Upregulation of long noncoding RNA Lnc‐IRF2‐3 and Lnc‐ZNF667‐AS1 is associated with poor survival in B‐chronic lymphocytic leukemia

Immunopeptidomics-Guided Warehouse Design for Peptide-Based Immunotherapy in Chronic Lymphocytic Leukemia

Contact Info

Product

Resources

About