当前位置： SCI文献检索 > LEUKEMIA RESEARCH期刊下所有文献 > A diphtheria toxin interleukin-3 fusion protein synergizes with tyrosine kinase inhibitors in killing leukemic progenitors from BCR/ABL positive acute leukemia.

A diphtheria toxin interleukin-3 fusion protein synergizes with tyrosine kinase inhibitors in killing leukemic progenitors from BCR/ABL positive acute leukemia.

Abstract：

: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 (DT(388)IL3) 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 DT(388)IL3 correlated with the level of IL-3Ralpha subunit by FACS. DT(388)IL3 synergized with both imatinib and dasatinib for killing of malignant CFCs. Long-term suspension culture-initiating cells (SC-ICs) and quiescent leukemic cells (G(0) in cell cycle) also were studied and synergistic interactions were again demonstrated. Thus, cotreatment with TKIs and DT(388)IL3 is much more effective in eliminating Ph(+) leukemic progenitors that express IL-3R than either agent alone.

journal_name

Leuk Res

journal_title

Leukemia research

authors

Kim HP,Frankel AE,Hogge DE

doi

10.1016/j.leukres.2009.12.008

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

1035-42

issue

8

eissn

0145-2126

issn

1873-5835

pii

S0145-2126(09)00581-5

journal_volume

34

pub_type

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