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rdf:type |
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lifeskim:mentions |
umls-concept:C0012550,
umls-concept:C0017262,
umls-concept:C0021757,
umls-concept:C0023467,
umls-concept:C0080096,
umls-concept:C0162768,
umls-concept:C0185117,
umls-concept:C0205282,
umls-concept:C0368761,
umls-concept:C0596402,
umls-concept:C0681842,
umls-concept:C0870134,
umls-concept:C1257890,
umls-concept:C1512658,
umls-concept:C1704788,
umls-concept:C1711351,
umls-concept:C2911684
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pubmed:issue |
10
|
|
pubmed:dateCreated |
2006-11-6
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pubmed:abstractText |
The interleukin-3 receptor (IL-3R) subunits are overexpressed on acute myeloid leukemia (AML) blasts compared with normal hematopoietic cells and are thus potential targets for novel therapeutic agents. Both fluorescence-activated cell sorter (FACS) analysis and quantitative real-time reverse transcription-polymerase chain reaction (QRT-PCR) were used to quantify expression of the IL-3Ralpha and beta(c) subunits on AML cells. QRT-PCR for both subunits was most predictive of killing of AML colony-forming cells (AML-CFCs) by diphtheria toxin-IL-3 fusion protein (DT(388)IL3). Among 19 patient samples, the relative level of the IL-3Ralpha was higher than the IL-3Rbeta(c) and highest in CD34(+)CD38(-)CD71(-) cells, enriched for candidate leukemia stem cells, compared with cell fractions depleted of such progenitors. Overall, the amount of IL-3Rbeta(c) subunit did not vary among sorted subpopulations. However, expression of both subunits varied by more than 10-fold among different AML samples for all subpopulations studied. The level of IL-3Rbeta(c) expression versus glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (set at 1000) ranged from 0.14 to 13.56 in CD34(+)CD38(-)CD71(-) cells from different samples; this value was correlated (r = .76, P = .05) with the ability of DT(388)IL3 to kill AML progenitors that engraft in beta(2)-microglobin-deficient nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice (n = 7). Thus, quantification of IL-3R subunit expression on AML blasts predicts the effectiveness IL-3R-targeted therapy in killing primitive leukemic progenitors.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
108
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3530-7
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16882709-Acute Disease,
pubmed-meshheading:16882709-Adolescent,
pubmed-meshheading:16882709-Adult,
pubmed-meshheading:16882709-Aged,
pubmed-meshheading:16882709-Animals,
pubmed-meshheading:16882709-Antineoplastic Agents,
pubmed-meshheading:16882709-Blast Crisis,
pubmed-meshheading:16882709-Cytokine Receptor Common beta Subunit,
pubmed-meshheading:16882709-Diphtheria Toxin,
pubmed-meshheading:16882709-Drug Delivery Systems,
pubmed-meshheading:16882709-Female,
pubmed-meshheading:16882709-Humans,
pubmed-meshheading:16882709-Immunophenotyping,
pubmed-meshheading:16882709-Interleukin-3 Receptor alpha Subunit,
pubmed-meshheading:16882709-Leukemia, Myeloid,
pubmed-meshheading:16882709-Male,
pubmed-meshheading:16882709-Mice,
pubmed-meshheading:16882709-Mice, SCID,
pubmed-meshheading:16882709-Middle Aged,
pubmed-meshheading:16882709-Neoplasm Proteins,
pubmed-meshheading:16882709-Neoplasms, Experimental,
pubmed-meshheading:16882709-Neoplastic Stem Cells,
pubmed-meshheading:16882709-Predictive Value of Tests,
pubmed-meshheading:16882709-Prognosis,
pubmed-meshheading:16882709-Receptors, Interleukin-3,
pubmed-meshheading:16882709-Recombinant Fusion Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
Expression of interleukin-3 receptor subunits on defined subpopulations of acute myeloid leukemia blasts predicts the cytotoxicity of diphtheria toxin interleukin-3 fusion protein against malignant progenitors that engraft in immunodeficient mice.
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pubmed:affiliation |
Terry Fox Laboratory, BC Cancer Agency, 675 West 10th Ave, Vancouver, BC V5Z 1L3 Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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