Publications by authors named "Anastasia Tikhonova"

Article Synopsis
  • T-lineage acute lymphoblastic leukemia (ALL) presents as an aggressive cancer with diverse subtypes, making traditional classification difficult.
  • A multiomics analysis of bone marrow samples revealed a specific subset of T-lineage ALL with active inflammatory and stem gene programs, showing unique biological and treatment response characteristics.
  • A computational inflammatory gene signature scoring system was developed to better classify patients, identifying a high-risk subtype that could guide targeted therapies for more effective treatment approaches.
View Article and Find Full Text PDF

Innate-like splenic marginal zone (MZ) B (MZB) cells play unique roles in immunity due to their rapid responsiveness to blood-borne microbes. How MZB cells integrate cell-extrinsic and -intrinsic processes to achieve accelerated responsiveness is unclear. We found that Delta-like1 (Dll1) Notch ligands in splenic fibroblasts regulated MZB cell pool size, migration, and function.

View Article and Find Full Text PDF

Acute myeloid leukemia (AML) is a devastating disease initiated and maintained by a rare subset of cells called leukemia stem cells (LSCs). LSCs are responsible for driving disease relapse, making the development of new therapeutic strategies to target LSCs urgently needed. The use of mass spectrometry-based metabolomics profiling has enabled the discovery of unique and targetable metabolic properties in LSCs.

View Article and Find Full Text PDF
Article Synopsis
  • * Sirtuin 3 (SIRT3), a regulator of oxidative phosphorylation (OXPHOS), is crucial for the survival of human LSC but not for normal blood stem cells, indicating its potential as a treatment target.
  • * By studying LSC's response to SIRT3 inhibition, researchers found ways to enhance LSC death, such as disrupting cholesterol balance and combining SIRT3 inhibition with a specific cancer drug, suggesting new treatment avenues for AML.
View Article and Find Full Text PDF

Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor prognosis and limited treatment options. Here we provide a comprehensive census of the bone marrow immune microenvironment in adult and pediatric patients with AML. We characterize unique inflammation signatures in a subset of AML patients, associated with inferior outcomes.

View Article and Find Full Text PDF

In their paper the authors describe distinct transcriptomic changes associated to treatment response in core bone marrow biopsies from patients with acute myeloid leukaemia. This finding raises the possibility that stratifying patients for treatment according to their transcriptomic profiles could improve patients' response and prognosis. Commentary on: Treaba et al.

View Article and Find Full Text PDF

Plants synthetize a large spectrum of secondary metabolites with substantial structural and functional diversity, making them a rich reservoir of new biologically active compounds. Among different plant lineages, the evolutionarily ancient branch of non-vascular plants (Bryophytes) is of particular interest as these organisms produce many unique biologically active compounds with highly promising antibacterial properties. Here, we characterized antibacterial activity of metabolites produced by different ecotypes (strains) of the model mosses Physcomitrium patens and Sphagnum fallax.

View Article and Find Full Text PDF

Mammalian cells autonomously activate hypoxia-inducible transcription factors (HIFs) to ensure survival in low-oxygen environments. We report here that injury-induced hypoxia is insufficient to trigger HIF1α in damaged epithelium. Instead, multimodal single-cell and spatial transcriptomics analyses and functional studies reveal that retinoic acid-related orphan receptor γt (RORγt) γδ T cell-derived interleukin-17A (IL-17A) is necessary and sufficient to activate HIF1α.

View Article and Find Full Text PDF

Despite improvements in outcomes for children with B- and T-cell acute lymphoblastic leukemia (B-ALL and T-ALL), patients with resistant or relapsed disease fare poorly. Previous studies have demonstrated the essential role of cyclin D3 in T-ALL disease initiation and progression and that targeting of the CDK4/6-cyclin D complex can suppress T-ALL proliferation, leading to efficient cell death in animal models. Studies in leukemia and other malignancies, suggest that schedule is important when combining CDK4/6 inhibitors (CDKi) with cytotoxic agents.

View Article and Find Full Text PDF
Article Synopsis
  • Multiple myeloma (MM) is characterized by tumor growth in the bones and the presence of multiple tumor sites, indicating disease progression and spreading patterns.
  • A study using a specific mouse model revealed that CD169+ tissue-resident macrophages play a crucial role in the early spread of myeloma from the bone marrow to other bones, where depleting these macrophages improved survival rates.
  • The dissemination of myeloma cells is linked to increased inflammation and the production of key cytokines (IL-6 and TNFα) by tumor-associated macrophages, which enhance cancer cell movement and vascular permeability, suggesting inflammation in bone marrow foci regulates myeloma cell egress.
View Article and Find Full Text PDF

Single-cell sequencing approaches have transformed our understanding of stem cell systems, including hematopoiesis and its niche within the bone marrow. Recent reports examined the bone marrow microenvironment at single-cell resolution at steady state, following chemotherapy treatment, leukemic onset, and aging. These rapid advancements significantly informed our understanding of bone marrow niche heterogeneity.

View Article and Find Full Text PDF

Single-cell sequencing approaches offer exploration of tissue architecture at unprecedented resolution. These tools are especially powerful when deconvoluting highly specialized microenvironments, such as stem cell (SC) niches. Here, we review single-cell studies that map the cellular and transcriptional makeup of stem and progenitor niches and discuss how these high-resolution analyses fundamentally advance our understanding of how niche factors shape SC biology and activity.

View Article and Find Full Text PDF

A subset of B cell acute lymphoblastic leukemia (B-ALL) patients will relapse and succumb to therapy-resistant disease. The bone marrow microenvironment may support B-ALL progression and treatment evasion. Utilizing single-cell approaches, we demonstrate B-ALL bone marrow immune microenvironment remodeling upon disease initiation and subsequent re-emergence during conventional chemotherapy.

View Article and Find Full Text PDF

During normal T cell development in the thymus, αβ TCRs signal immature thymocytes to differentiate into mature T cells by binding to peptide-MHC ligands together with CD4/CD8 coreceptors. Conversely, in MHC and CD4/CD8 coreceptor-deficient mice, the thymus generates mature T cells expressing MHC-independent TCRs that recognize native conformational epitopes rather than linear antigenic-peptides presented by MHC. To date, no structural information of MHC-independent TCRs is available, and their structural recognition of non-MHC ligand remains unknown.

View Article and Find Full Text PDF

The response to systemic infection and injury requires the rapid adaptation of hematopoietic stem cells (HSCs), which proliferate and divert their differentiation toward the myeloid lineage. Significant interest has emerged in understanding the signals that trigger the emergency hematopoietic program. However, the mechanisms that halt this response of HSCs, which is critical to restore homeostasis, remain unknown.

View Article and Find Full Text PDF

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

View Article and Find Full Text PDF

The bone marrow microenvironment has a key role in regulating haematopoiesis, but its molecular complexity and response to stress are incompletely understood. Here we map the transcriptional landscape of mouse bone marrow vascular, perivascular and osteoblast cell populations at single-cell resolution, both at homeostasis and under conditions of stress-induced haematopoiesis. This analysis revealed previously unappreciated levels of cellular heterogeneity within the bone marrow niche and resolved cellular sources of pro-haematopoietic growth factors, chemokines and membrane-bound ligands.

View Article and Find Full Text PDF

The αβ T cell receptor (TCR) repertoire on mature T cells is selected in the thymus, but the basis for thymic selection of MHC-restricted TCRs from a randomly generated pre-selection repertoire is not known. Here we perform comparative repertoire sequence analyses of pre-selection and post-selection TCR from multiple MHC-sufficient and MHC-deficient mouse strains, and find that MHC-restricted and MHC-independent TCRs are primarily distinguished by features in their non-germline CDR3 regions, with many pre-selection CDR3 sequences not compatible with MHC-binding. Thymic selection of MHC-independent TCR is largely unconstrained, but the selection of MHC-specific TCR is restricted by both CDR3 length and specific amino acid usage.

View Article and Find Full Text PDF

T cell acute lymphoblastic leukemia (T-ALL) is commonly associated with activating mutations in the NOTCH1 pathway. Recent reports have shown a link between NOTCH1 signaling and intracellular Ca homeostasis in T-ALL. Here, we investigate the role of store-operated Ca entry (SOCE) mediated by the Ca channel ORAI1 and its activators STIM1 and STIM2 in T-ALL.

View Article and Find Full Text PDF

The role of the microenvironment in T cell acute lymphoblastic leukemia (T-ALL), or any acute leukemia, is poorly understood. Here we demonstrate that T-ALL cells are in direct, stable contact with CXCL12-producing bone marrow stroma. Cxcl12 deletion from vascular endothelial, but not perivascular, cells impeded tumor growth, suggesting a vascular niche for T-ALL.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessiont4gjl9nt57cajn7qlnvu7u7u0jktstdd): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once