J Immunother
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Published: May 2012
Cross-presentation is an important mechanism by which exogenous tumor antigens are presented to elicit immunity. Because neutrophil elastase (NE) and proteinase-3 (P3) expression is increased in myeloid leukemia, we investigated whether NE and P3 are cross-presented by dendritic cells (DC) and B cells, and whether the NE and P3 source determines immune outcomes. We show that NE and P3 are elevated in leukemia patient serum and that levels correlate with remission status. We demonstrate cellular uptake of NE and P3 into lysosomes, ubiquitination, and proteasome processing for cross-presentation. Using anti-PR1/human leukocyte antigen-A2 monoclonal antibody, we provide direct evidence that B-cells cross-present soluble and leukemia-associated NE and P3, whereas DCs cross-present only leukemia-associated NE and P3. Cross-presentation occurred at early time points but was not associated with DC or B-cell activation, suggesting that NE and P3 cross-presentation may favor tolerance. Furthermore, we show aberrant subcellular localization of NE and P3 in leukemia blasts to compartments that share common elements of the classic major histocompatibility class I antigen-presenting pathway, which may facilitate cross-presentation. Our data demonstrate distinct mechanisms for cross-presentation of soluble and cell-associated NE and P3, which may be valuable in understanding immunity to PR1 in leukemia.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326226 | PMC |
http://dx.doi.org/10.1097/CJI.0b013e31824b3b14 | DOI Listing |
BMJ Case Rep
January 2025
Department of Internal Medicine, University of Kentucky, Lexington, Kentucky, USA.
BCR::ABL1-like B-lymphoblastic leukaemia (B-ALL) neoplasms lack the BCR::ABL1 translocation but have a gene expression profile like BCR::ABL1 positive B-ALL. This includes alterations in cytokine receptors and signalling genes, such as and Cases with CRLF2 rearrangements account for approximately 50% of cases of Philadelphia-like acute lymphoblastic leukaemia (Ph-like ALL), and the frequency of specific genomic lesions varies with ethnicity such that IGH::CRLF2 translocations are more common in Hispanics and Native Americans.We report two cases of BCR::ABL1-like ALL, with significant eosinophilia.
View Article and Find Full Text PDFCureus
December 2024
Medical Oncology, Jawaharlal Nehru Medical College, Wardha, IND.
Gynecomastia, the abnormal enlargement of male breast tissue, is a rare side effect associated with dasatinib. This drug is used in the treatment of chronic myeloid leukemia (CML). We present a case of dasatinib-induced gynecomastia in a 52-year-old gentleman with CML who developed bilateral breast enlargement and tenderness after approximately four months of dasatinib treatment.
View Article and Find Full Text PDFHistochem Cell Biol
January 2025
Department of Histology and Embryology, Faculty of Medicine, Ankara Yildirim Beyazit University, 06800, Ankara, Turkey.
Bone marrow mesenchymal stromal cells (BM-MSCs) are integral components of the bone marrow microenvironment, playing a crucial role in supporting hematopoiesis. Recent studies have investigated the potential involvement of BM-MSCs in the pathophysiology of acute lymphoblastic leukemia (ALL). However, the exact contribution of BM-MSCs to leukemia progression remains unclear because of conflicting findings and limited characterization.
View Article and Find Full Text PDFHematol Oncol
January 2025
University of California Irvine, Irvine, California, USA.
Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues.
View Article and Find Full Text PDFDrug Resist Updat
January 2025
Loma Linda University Cancer Center, Loma Linda, CA 92354, United States; Department of Basic Sciences, Loma Linda University, Loma Linda, CA 92354, United States. Electronic address:
Chromosomal rearrangements (CR) initiate leukemogenesis in approximately 50 % of acute myeloid leukemia (AML) patients; however, limited targeted therapies exist due to a lack of accurate molecular and genetic biomarkers of refractory mechanisms during treatment. Here, we investigated the pathological landscape of treatment resistance and relapse in 16 CR-AML patients by monitoring cytogenetic, RNAseq, and genome-wide changes among newly diagnosed, refractory, and relapsed AML. First, in FISH-diagnosed KMT2A (MLL gene, 11q23)/AFDN (AF6, 6q27)-rearrangement, RNA-sequencing identified an unknown CCDC32 (15q15.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!
© LitMetric 2025. All rights reserved.