P-glycoprotein (PGP) over-expression on malignant cells is associated with poor prognosis and treatment outcome due to the development of a multidrug resistance phenotype. In this study, we analyzed the correlation between expression of PGP and lymphoid antigens (Ly) on leukemic myeloblasts versus response to therapy and survival in acute myeloid leukemia (AML). Fifty-one consecutive patients, aged 16-75 (median age 44.6 years), diagnosed with de novo AML between 1997 and 2000, and who received at least one induction chemotherapy course, were enrolled in the study. Expression of PGP on ≥ 10% of the myeloblasts (PGP(+)AML) at the time of diagnosis was observed in 21 patients (41%). The complete remission rate did not differ between PGP(+) (13/21) and PGP(-) (20/30) patients (62 vs. 67%). Twelve of the 51 patients (24%) were still alive after a median follow-up time of 11.5 years (range 10.7-13.1). The Ly(+)AML patients showed significantly better overall survival compared with Ly(-)AML patients (8/18 vs. 4/33 patients alive at the last follow-up, P = 0.003). The subgroup of patients with co-expression of PGP and Ly also showed better overall survival compared with PGP(+)AML patients without Ly expression (4/8 vs. 0/13 patients alive at the last follow-up; P = 0.04). Our results suggest that expression of lymphoid antigens on PGP(+) myeloblasts in AML can positively affect survival in AML patients, mainly due to a decreased relapse risk and better survival. Although the small number of patient may be perceived as a limitation of the study, the long follow-up period strengthens its value. Further prospective trials are needed to obtain more information concerning the association between PGP and lymphoid antigens in AML, which would put our results in their ultimate proper context.
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ACS Nano
January 2025
Department of Cancer Biology and Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, United States.
Extracellular vesicles (EVs) are generated in all cells. Systemic administration of allogenic EVs derived from epithelial and mesenchymal cells has been shown to be safe, despite carrying an array of functional molecules, including thousands of proteins. To address whether epithelial cell-derived EVs can be modified to acquire the capacity to induce an immune response, we engineered 293T EVs to harbor the immunomodulatory molecules CD80, OX40L, and PD-L1.
View Article and Find Full Text PDFbioRxiv
January 2025
Department of Chemistry, 409 McCormick Road, University of Virginia, Charlottesville, VA 22904.
Antibody production is central to protection against new pathogens and cancers, as well as to certain forms of autoimmunity. Antibodies often originate in the lymph node (LN), specifically at the extrafollicular border of B cell follicles, where T and B lymphocytes physically interact to drive B cell maturation into antibody-secreting plasmablasts. In vitro models of this process are sorely needed to predict aspects of the human immune response.
View Article and Find Full Text PDFFront Immunol
January 2025
Center for Bioscience Research and Education, Utsunomiya University, Utsunomiya, Japan.
The cellular and molecular mechanisms underlying lymphocyte development are diverse among teleost species. Although recent scRNA-seq analyses of zebrafish hematopoietic cells have advanced our understanding of teleost hematopoiesis, comparative studies using another genetic model, medaka, which is evolutionarily distant among teleosts, is useful for understanding commonality and species-specificity in teleosts. In order to gain insight into how different molecular and cellular mechanisms of lymphocyte development in medaka and zebrafish, we established a () mutant medaka, which exhibited defects in V(D)J rearrangement of lymphocyte antigen receptor genes, accordingly lacking mature B and T cells.
View Article and Find Full Text PDFViruses
January 2025
Department of Avian and Rabbit Medicine, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.
The present study aims to better understand the nature of currently circulating GPV strains and their pathological impact on the immune system during natural outbreaks among different duck breeds in Egypt. For this purpose, 99 ducks (25 flocks) of different breeds, aged 14-75 days, were clinically examined, and 75 tissue pools from the thymus, bursa of Fabricius, and spleen were submitted for virus detection and identification. Clinical and postmortem findings were suggestive of GPV infection.
View Article and Find Full Text PDFNat Commun
January 2025
Division of Hematology & Oncology, Department of Medicine, School of Medicine, University of California, Irvine, CA, 92697, USA.
NKp46 is a critical regulator of natural killer (NK) cell immunity, but its function in non-NK innate immune cells remains unclear. Here, we show that NKp46 is indispensable for expressing IL-2 receptor-α (IL-2Rα) by non-NK liver-resident type-1 innate lymphoid cells (ILC1s). Deletion of NKp46 reduces IL-2Rα on ILC1s by downregulating NF-κB signaling, thus impairing ILC1 proliferation and cytotoxicity in vitro and in vivo.
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