Background: CD33 is a well-known stem cell target in acute myeloid leukemia. So far, however, little is known about expression of CD33 on leukemic stem cells in chronic leukemias.
Design And Methods: We analyzed expression of CD33 in leukemic progenitors in chronic myeloid leukemia by multi-color flow cytometry and quantitative polymerase chain reaction. In addition, the effects of a CD33-targeting drug, gemtuzumab/ozogamicin, were examined.
Results: As assessed by flow cytometry, stem cell-enriched CD34(+)/CD38(-)/CD123(+) leukemic cells expressed significantly higher levels of CD33 compared to normal CD34(+)/CD38(-) stem cells. Moreover, highly enriched leukemic CD34(+)/CD38(-) cells (>98% purity) displayed higher levels of CD33 mRNA. In chronic phase patients, CD33 was found to be expressed invariably on most or all stem cells, whereas in accelerated or blast phase of the disease, the levels of CD33 on stem cells varied from donor to donor. The MDR1 antigen, supposedly involved in resistance against ozogamicin, was not detectable on leukemic CD34(+)/CD38(-) cells. Correspondingly, gemtuzumab/ozogamicin produced growth inhibition in leukemic progenitor cells in all patients tested. The effects of gemtuzumab/ozogamicin were dose-dependent, occurred at low concentrations, and were accompanied by apoptosis in suspension culture. Moreover, the drug was found to inhibit growth of leukemic cells in a colony assay and long-term culture-initiating cell assay. Finally, gemtuzumab/ozogamicin was found to synergize with nilotinib and bosutinib in inducing growth inhibition in leukemic cells.
Conclusions: CD33 is expressed abundantly on immature CD34(+)/CD38(-) stem cells and may serve as a stem cell target in chronic myeloid leukemia.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269481 | PMC |
| http://dx.doi.org/10.3324/haematol.2010.035006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
hUC-MSCs Prevent Acute High-Altitude Injury through Apoe/Pdgf-b/p-Erk1/2 Axis in Mice.
Stem Cell Rev Rep
January 2025
Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Background: The hypobaric hypoxic atmosphere can cause adverse reactions or sickness. The purpose of this study was to explore the preventive effect and mechanism of human umbilical cord mesenchymal stem cells (hUC-MSCs) on acute pathological injury in mice exposed to high-altitude.
Methods: We pretreated C57BL/6 mice with hUC-MSCs via the tail vein injection, and then the mice were subjected to hypobaric hypoxic conditions for five days.
Adipose-derived stem cells regulate mitochondrial dynamics to alleviate the aging of HFF-1 cells.
In Vitro Cell Dev Biol Anim
January 2025
Department of Outpatient Service, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, Hunan, China.
The objective of this study is to explore how adipose-derived stem cells (ASCs) regulate mitochondrial structure and function and the impact of this regulation on slowing cellular senescence. HFF-1 cells were induced by HO to establish a cellular senescence model, and ASCs or Mdivi-1 (mitochondrial fission inhibitor) was added. MTT examined the cell proliferation; flow cytometry detected mitochondrial membrane potential as well as apoptosis and cell cycle; kit measured ATP production; ELISA analyzed the levels of interleukin-6 (IL-6), interleukin 1 beta (IL-1β), tumor necrosis factor alpha-like (TNF-α), glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD); Western blotting and qRT-PCR detected the expression of protein and mRNA levels; and β-galactosidase staining observed the degree of cellular senescence.
View Article and Find Full Text PDFAge-dependent differences in breast tumor microenvironment: challenges and opportunities for efficacy studies in preclinical models.
Cell Death Differ
January 2025
Laboratory of Hematology-Oncology, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy.
Immunity suffers a function deficit during aging, and the incidence of cancer is increased in the elderly. However, most cancer models employ young mice, which are poorly representative of adult cancer patients. We have previously reported that Triple-Therapy (TT), involving antigen-presenting-cell activation by vinorelbine and generation of TCF1-stem-cell-like T cells (scTs) by cyclophosphamide significantly improved anti-PD-1 efficacy in anti-PD1-resistant models like Triple-Negative Breast Cancer (TNBC) and Non-Hodgkin's Lymphoma (NHL), due to T-cell-mediated tumor killing.
View Article and Find Full Text PDFCrosstalk between GLTSCR1-deficient endothelial cells and tumour cells promotes colorectal cancer development by activating the Notch pathway.
Cell Death Differ
January 2025
Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital (Yiwu), Zhejiang University School of Medicine, Hangzhou, 310058, China.
Cancer stem cells (CSCs) typically reside in perivascular niches, but whether endothelial cells of blood vessels influence the stemness of cancer cells remains poorly understood. This study revealed that endothelial cell-specific GLTSCR1 deletion promotes colorectal cancer (CRC) tumorigenesis and metastasis by increasing cancer cell stemness. Mechanistically, knocking down GLTSCR1 induces the transformation of endothelial cells into tip cells by regulating the expression of Neuropilin-1 (NRP1), thereby increasing the direct contact and interaction between endothelial cells and tumour cells.
View Article and Find Full Text PDFStem cells prevent long-term deterioration of renal function after renal artery revascularization in a renovascular hypertension model in rats.
Sci Rep
January 2025
Renal Division, Department of Medicine, Universidade Federal de São Paulo, Rua Pedro de Toledo, 781, São Paulo, SP, 04039-032, Brazil.
Partial stenosis of the renal artery causes renovascular hypertension (RVH) and is accompanied by chronic renal ischemia, resulting in irreversible kidney damage. Revascularization constitutes the most efficient therapy for normalizing blood pressure (BP) and has significant benefits for renal function; however, the tissue damage caused by chronic hypoxia is not fully reversed. Mesenchymal stem cells (MSCs) have produced discrete results in minimizing RVH and renal tissue and functional improvements since the obstruction persists.
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!