Understanding the mechanisms leading to transformation of early B-lineage precursors is an important step leading to rational design of new treatments for precursor (pre)-B-cell leukemia. We used normal mouse pre-B cells to determine if and how transforming growth factor (TGF)-beta1 affects these precursors to the B-cell lineage and whether transformed pre-B cells respond to TGF-beta1. We found that normal pre-B cells proliferating in the presence of interleukin (IL)-7 enter cell-cycle arrest after exposure to TGF-beta1. However, clonally related IL-7-independent tumors induced by oncogenes abl + myc or raf + myc have reduced sensitivity to TGF-beta1. In contrast, tumor cells induced by myc alone remain sensitive to TGF-beta1 growth suppression. These results suggest that lesions in different molecular signaling pathways can lead to loss of TGF-beta1 sensitivity in a single cell type. The approach of using normal pre-B-cell lines and transformation by overexpression of different oncogenes provides a system to compare and contrast molecular pathways that lead to full malignancy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1634/stemcells.2005-0623 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Selenoprotein-Mediated Redox Regulation Shapes the Cell Fate of HSCs and Mature Lineages.
Blood
January 2025
Graduate School of Medicine and Frontier Biosciences, Osaka University, Japan.
The maintenance of cellular redox balance is crucial for cell survival and homeostasis and is disrupted with aging. Selenoproteins, comprising essential antioxidant enzymes, raise intriguing questions about their involvement in hematopoietic aging and potential reversibility. Motivated by our observation of mRNA downregulation of key antioxidant selenoproteins in aged human hematopoietic stem cells (HSCs) and previous findings of increased lipid peroxidation in aged hematopoiesis, we employed tRNASec gene (Trsp) knockout (KO) mouse model to simulate disrupted selenoprotein synthesis.
View Article and Find Full Text PDFHow to think about acute leukemia of ambiguous lineage.
Hematology Am Soc Hematol Educ Program
December 2024
UT Southwestern Medical Center, BioCenter, Dallas, TX.
Classification of acute leukemia involves assigning lineage by resemblance of blasts to normal progenitor cells. This approach provides descriptive information that is useful for disease monitoring, provides clues to pathogenesis, and can help to select effective chemotherapeutic regimens. Acute leukemias of ambiguous lineage (ALAL) are those leukemias that either fail to show evidence of myeloid, B-lymphoid, or T-lymphoid lineage commitment or show evidence of commitment to more than 1 lineage, including mixed-phenotype acute leukemia (MPAL).
View Article and Find Full Text PDFDissecting L-glutamine metabolism in acute myeloid leukemia: single-cell insights and therapeutic implications.
J Transl Med
November 2024
The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China.
Background: Acute myeloid leukemia (AML) is a rapidly progressing blood cancer. The prognosis of AML can be challenging, emphasizing the need for ongoing research and innovative approaches to improve outcomes in individuals affected by this formidable hematologic malignancy.
Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) from AML patients to investigate the impact of L-glutamine metabolism-related genes on disease progression.
Potential molecular mechanisms of ETV6-RUNX1-positive B progenitor cell cluster in acute lymphoblastic leukemia revealed by single-cell RNA sequencing.
PeerJ
November 2024
Neurosurgery Department, Jinzhou Central Hospital, Jinzhou, China.
Article Synopsis
- The study aimed to investigate the immune landscape and immune cell roles in the progression of acute lymphoblastic leukemia (ALL), focusing particularly on the ETV6-RUNX1 genetic alteration common in childhood cases.
- Using advanced techniques like single-cell RNA sequencing, researchers analyzed B progenitor cells from bone marrow samples, identifying specific gene expressions and pathways that may drive rapid cell cycle progression in ALL.
- Results highlighted distinct clusters of B progenitor cells, particularly one with amplified genes on chromosome 6p that were linked to increased cell cycle activity, underscoring the complexity of immune interactions in the disease's progression.
DNA damage-induced p53 downregulates expression of RAG1 through a negative feedback loop involving miR-34a and FOXP1.
J Biol Chem
December 2024
Department of Pathology, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, The Netherlands; Lymphoma and Myeloma Center Amsterdam (LYMMCARE), Amsterdam, The Netherlands. Electronic address:
During the maturation of pre-B cells, the recombination activating gene 1 and 2 (RAG1/2) endonuclease complex plays a crucial role in coordinating V(D)J recombination by introducing DNA breaks in immunoglobulin (Ig) loci. Dysregulation of RAG1/2 has been linked to the onset of B cell malignancies, yet the mechanisms controlling RAG1/2 in pre-B cells exposed to excessive DNA damage are not fully understood. In this study, we show that DNA damage-induced activation of p53 initiates a negative-feedback loop which rapidly downregulates RAG1 levels.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!