Alexey V. Danilov
A5067633124- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- CAR-T cell therapy research
- T-cell and Retrovirus Studies
- Cancer-related Molecular Pathways
- Viral-associated cancers and disorders
- Microtubule and mitosis dynamics
- Chronic Myeloid Leukemia Treatments
- Acute Lymphoblastic Leukemia research
- Advanced Breast Cancer Therapies
- Cell death mechanisms and regulation
- Immunodeficiency and Autoimmune Disorders
- Cancer-related gene regulation
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- CNS Lymphoma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Galectins and Cancer Biology
- Retinoids in leukemia and cellular processes
- Lung Cancer Treatments and Mutations
- Peptidase Inhibition and Analysis
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
City Of Hope National Medical Center
2020-2025
City of Hope
2020-2025
Beckman Research Institute
2021-2024
Oregon Health & Science University
2014-2023
OHSU Knight Cancer Institute
2015-2023
Northern (Arctic) Federal University
2017-2020
Dartmouth–Hitchcock Medical Center
2011-2018
State Budget Institution of Health St. Petersburg Clinical Research Center Specialized Types of Medical Care
2018
John Wiley & Sons (United States)
2018
Dartmouth College
2011-2016
Abstract To study mechanisms underlying resistance to the BCL2 inhibitor venetoclax in acute myeloid leukemia (AML), we used a genome-wide CRISPR/Cas9 screen identify gene knockouts resulting drug resistance. We validated TP53, BAX, and PMAIP1 as genes whose inactivation results AML cell lines. Resistance resulted from an inability execute apoptosis driven by BAX loss, decreased expression of BCL2, and/or reliance on alternative family members such BCL2L1. The was accompanied changes...
Acute myeloid leukemia (AML) is a cancer of myeloid-lineage cells with limited therapeutic options. We previously combined ex vivo drug sensitivity genomic, transcriptomic, and clinical annotations for large cohort AML patients, which facilitated discovery functional genomic correlates. Here, we present dataset that has been harmonized our initial report to yield cumulative 805 patients (942 specimens). show strong cross-cohort concordance identify features response. Further, deconvoluting...
Stromal-mediated signaling enhances NF-κB pathway activity in chronic lymphocytic leukemia (CLL) B cells, leading to cell survival and chemoresistance. Ubiquitination of IκBα may partially account for constitutive activation NF-κB. MLN4924 is an investigational agent that inhibits the Nedd8-activating enzyme, thereby neutralizing Cullin-RING ubiquitin ligases preventing degradation their substrates.We conducted a preclinical assessment CLL. Primary CLL cells were cocultured vitro with...
To examine the effect of a strong cytochrome P450 (CYP) 3A inhibitor, ketoconazole, on pharmacokinetics, safety and tolerability venetoclax.
Mantle cell lymphoma (MCL) is a phenotypically and genetically heterogeneous malignancy in which the genetic alterations determining clinical indications are not fully understood. Here, we performed comprehensive whole-exome sequencing analysis of 152 primary samples derived from 134 MCL patients, including longitudinal 16 patients matched RNA-Seq data 48 samples. We classified into 4 robust clusters (C1-C4). C1 featured mutated immunoglobulin heavy variable (IGHV), CCND1 mutation,...
Chimeric antigen receptor T-cell therapy (CART) has extended survival of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). However, limited durability response and prevalent toxicities remain problematic. Identifying who are at high risk disease progression, toxicity, death would inform treatment decisions. Although the cumulative illness rating scale (CIRS) been shown to correlate in malignancies, no prognostic score independently validated CART recipients. We...
BACKGROUND Most patients with chronic lymphocytic leukemia (CLL) present multiple comorbidities. Although comorbidities negatively affect outcomes for treated chemoimmunotherapy, their impact on who receive targeted therapies is unknown. METHODS This multicenter, retrospective analysis evaluated the significance of comorbidities, as assessed by Cumulative Illness Rating Scale (CIRS), among CLL ibrutinib. RESULTS One hundred forty‐five received ibrutinib (80% in a relapsed/refractory...
Bruton tyrosine kinase (BTK) inhibition alone leads to incomplete responses in chronic lymphocytic leukemia (CLL). Combination therapy may reduce activation of escape pathways and deepen responses. This open-label, phase Ib, sequential dose-escalation dose-expansion study evaluated the safety, tolerability, pharmacokinetics, preliminary efficacy selective BTK inhibitor tirabrutinib alone, combination with PI3K delta (PI3Kδ) idelalisib, or spleen (SYK) entospletinib patients...
Abstract Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) HIV-BL from 2008 to 2019 aiming identify prognostic factors and outcomes. With a median follow up 4.5 years, the 3-year progression-free survival (PFS) overall (OS) were 61% (95% confidence interval [CI] 55% 67%) 66% (95%CI 59% 71%), respectively, similar results both countries....
Most patients receiving chimeric antigen receptor T-cell therapy (CAR-T) for aggressive B-cell non-Hodgkin lymphoma (B-NHL) do not experience a durable remission. Several novel agents are approved to treat relapsed, refractory B-NHL; however, it remains unclear how sequence these therapies pre- and post-CAR-T. We conducted multicenter retrospective analysis describe peri-CAR-T practice patterns survival predictors CD19-directed CAR-T. Patients (n = 514) from 13 centers treated with CAR-T...
Abstract Diffuse large B-cell lymphoma (DLBCL) exhibits significant genetic heterogeneity which contributes to drug resistance, necessitating development of novel therapeutic approaches. Pharmacological inhibitors cyclin-dependent kinases (CDK) demonstrated pre-clinical activity in DLBCL, however many stalled clinical development. Here we show that AZD4573, a selective inhibitor CDK9, restricted growth DLBCL cells. CDK9 inhibition (CDK9i) resulted rapid changes the transcriptome and...
RNA splicing dysregulation underlies the onset and progression of cancers. In chronic lymphocytic leukemia (CLL), spliceosome mutations leading to aberrant occur in ∼20% patients. However, mechanism for defects spliceosome-unmutated CLL cases remains elusive. Through an integrative transcriptomic proteomic analysis, we discover that proteins involved are posttranscriptionally upregulated cells, resulting dysregulation. The abundance complexes is independent risk factor poor prognosis....