کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2138543 1087879 2010 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A diphtheria toxin interleukin-3 fusion protein synergizes with tyrosine kinase inhibitors in killing leukemic progenitors from BCR/ABL positive acute leukemia
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
A diphtheria toxin interleukin-3 fusion protein synergizes with tyrosine kinase inhibitors in killing leukemic progenitors from BCR/ABL positive acute leukemia
چکیده انگلیسی

Despite initial remissions, most patients with Ph chromosome positive (Ph+) acute leukemia (AL) become refractory to tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib. This study was designed to determine if targeting the interleukin-3 receptor (IL-3R) with a diphtheria toxin fusion protein (DT388IL3) would improve the effectiveness of TKIs against Ph+ AL cells. IL-3R subunits were detected on most Ph+ cells and the IC50 for killing of colony forming cell (CFC) with DT388IL3 correlated with the level of IL-3Rα subunit by FACS. DT388IL3 synergized with both imatinib and dasatinib for killing of malignant CFCs. Long-term suspension culture-initiating cells (SC-ICs) and quiescent leukemic cells (G0 in cell cycle) also were studied and synergistic interactions were again demonstrated. Thus, cotreatment with TKIs and DT388IL3 is much more effective in eliminating Ph+ leukemic progenitors that express IL-3R than either agent alone.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Leukemia Research - Volume 34, Issue 8, August 2010, Pages 1035–1042
نویسندگان
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