Abstract:
:While imatinib and other tyrosine kinase inhibitors (TKIs) are highly efficacious in the treatment of chronic myeloid leukaemia (CML), some patients become refractory to these therapies. After confirming that interleukin-3 receptor (IL3R, CD123) is highly expressed on CD34(+) /CD38(-) BCR-ABL1(+) CML stem cells, we investigated whether targeting IL3R with diphtheria toxin (DT)-IL3 fusion proteins SL-401 (DT388 -IL3) and SL-501 (DT388 -IL3[K116W]) could eradicate these stem cells. SL-401 and SL-501 inhibited cell growth and induced apoptosis in the KBM5 cell line and its TKI-resistant KBM5-STI subline. Combinations of imatinib with these agents increased apoptosis in KBM5 and in primary CML cells. In six primary CML samples, including CML cells harbouring the ABL1 T315I mutation, SL-401 and SL-501 decreased the absolute numbers of viable CD34(+) /CD38(-) /CD123(+) CML progenitor cells by inducing apoptosis. IL3-targeting agents reduced clonogenic growth and diminished the fraction of primitive long-term culture-initiating cells in samples from patients with advanced phase CML that were resistant to TKIs or harboured an ABL1 mutation. Survival was also extended in a mouse model of primary TKI-resistant CML blast crisis. These data suggest that the DT-IL3 fusion proteins, SL-401 and SL-501, deplete CML stem cells and may increase the effectiveness of current CML treatment, which principally targets tumour bulk.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Frolova O,Benito J,Brooks C,Wang RY,Korchin B,Rowinsky EK,Cortes J,Kantarjian H,Andreeff M,Frankel AE,Konopleva Mdoi
10.1111/bjh.12978subject
Has Abstractpub_date
2014-09-01 00:00:00pages
862-74issue
6eissn
0007-1048issn
1365-2141journal_volume
166pub_type
杂志文章abstract::We studied MDS-associated inhibitory activity, which inhibited colony formation in vitro of granulocyte-macrophage progenitors (CFU-GM). Macrophages obtained from MDS bone marrow mononuclear cells (BM-MNC) when pretreated with granulocyte-macrophage colony stimulating factor (GM-CSF) suppressed the growth of normal CF...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1990.tb02563.x
更新日期:1990-02-01 00:00:00
abstract::To investigate the role of neutrophils in complement-induced changes in vascular permeability, skin wheal and flare responses to intradermal injection of autologous activated serum complement were measured in normal and neutropenic subjects. In normal subjects, responses were dose-dependent and were abolished by remov...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1986.tb04131.x
更新日期:1986-10-01 00:00:00
abstract::In countries with a good standard of health care, intracranial haemorrhage (ICH) during the neonatal period affects 3.5-4.0% of all haemophilia boys, which is considerably (40-80 times) higher than expected in the normal population. ICHs are also frequent after the neonatal period, affecting 3-10% of the haemophilia p...
journal_title:British journal of haematology
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更新日期:2008-02-01 00:00:00
abstract::The TH line was established by bringing tumour cells from a multiple myeloma patient into suspension culture and subsequently cloning them by limiting dilution. The cultured cells show marked heterogeneity; there are ultrastructural differences between small and large TH cells, particularly with respect to the rough e...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1991.tb04526.x
更新日期:1991-10-01 00:00:00
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journal_title:British journal of haematology
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doi:10.1046/j.1365-2141.1996.d01-1691.x
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abstract::In an attempt to develop a model system for analysing iron metabolism in a relatively homogeneous population of early red cell precursors, the intracellular distribution of 59Fe was examined in Friend murine erythroleukaemic cells after induction of haemoglobin synthesis with dimethylsulphoxide. After incubation of th...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1983.tb02142.x
更新日期:1983-08-01 00:00:00
abstract::Non-endemic Burkitt lymphoma (BL) is a rare germinal centre B-cell-derived malignancy with the genetic hallmark of MYC gene translocation and with rapid tumour growth as a distinct clinical feature. To investigate treatment outcomes, loss of lifetime and relapse risk in adult BL patients treated with intensive immunoc...
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pub_type: 杂志文章,多中心研究
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journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.14719
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journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2141.2009.07765.x
更新日期:2009-09-01 00:00:00
abstract::We evaluated the additional benefit of Technetium(99)-sestamibi (99mTc-MIBI) scanning in comparison with standard X-ray techniques for multiple myeloma patients either at diagnosis or during follow-up. Between February 2001 and January 2005, 397 whole body scans were acquired. On 229 scans performed at diagnosis, 146 ...
journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2141.2006.06489.x
更新日期:2007-03-01 00:00:00
abstract::Standard treatment for classical Hodgkin lymphoma (cHL) is poorly tolerated in older patients and results disappointing. We assessed safety and efficacy of brentuximab vedotin (BV), in previously untreated patients with cHL unfit for standard treatment due to age, frailty or comorbidity. The primary outcome was comple...
journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.430973.x
更新日期:1996-03-01 00:00:00
abstract::Akt mediates growth and drug resistance in multiple myeloma (MM) cells in the bone marrow (BM) microenvironment. We have shown that a novel Akt inhibitor Perifosine induces significant cytotoxicity in MM cells in the BM milieu. This study further delineated molecular mechanisms whereby Perifosine triggered cytotoxicit...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2007.06714.x
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01712.x
更新日期:1999-11-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01271.x
更新日期:1999-03-01 00:00:00
abstract::We prospectively studied presentation biological differences and the response to therapy in patients with thrombotic thrombocytopenic purpura (TTP) associated with, or unrelated to human immunodeficiency virus (HIV) infection. TTP patients underwent standard evaluations and were treated with prednisone 1 mg/kg in addi...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2004.05325.x
更新日期:2005-02-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章,评审
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更新日期:2012-06-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1982.tb03913.x
更新日期:1982-11-01 00:00:00
abstract::Bortezomib in combination with cyclophosphamide and dexamethasone (CyBorD, is a well-established frontline chemotherapy regimen for patients with multiple myeloma, but prospective data on elderly non-transplant eligible patients is limited. A total of 155 patients aged 70 years or older with newly diagnosed multiple m...
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journal_title:British journal of haematology
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1986.tb02971.x
更新日期:1986-03-01 00:00:00
abstract:UNLABELLED:Transplant-related mortality (TRM) remains a major problem in older patients undergoing allogeneic haemopoietic stem cell transplants (HSCTs). We have therefore explored a less intensive conditioning in 33 patients with a median age of 52 years (range 43-60) transplanted from human leucocyte antigen (HLA)-id...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02123.x
更新日期:2000-06-01 00:00:00
abstract::Two children affected by severe aplastic anaemia (SAA) underwent allogeneic bone marrow transplantation (BMT) using partially matched family donors. In both cases there was a successful engraftment of donor haemopoietic stem cells. However, after an initial erythropoietic recovery, 5 months following BMT both children...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1992.tb04571.x
更新日期:1992-04-01 00:00:00
abstract::Tellurite (K2TeO3) has been suggested as a potential anti-sickling compound because it causes a selective increase in the water content of RBC. To investigate the conditions underlying the increase in RBC volume due to tellurite, normal RBCs were incubated with the compound in a physiological medium and the cells wash...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1988.tb02496.x
更新日期:1988-11-01 00:00:00
abstract::Neurological emergencies are frequently catastrophic events in the course of haematological malignancies (HM) that, if not promptly recognized and treated, may lead to lethal outcomes or chronic sequelae. They may occur at any time during the disease course, but are more frequently observed following relapse. Practice...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
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更新日期:2020-06-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.01103.x
更新日期:1998-12-01 00:00:00
abstract::We examined major histocompatibility complex (MHC) class II expression in B cells, peripheral blood monocytes, activated T cells, epidermal Langerhans cells, monocyte-derived dendritic cells, dermal microvascular endothelial cells (DMEC) and fibroblasts of twin brothers with MHC class II deficiency. Although residual ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.03105.x
更新日期:2001-11-01 00:00:00
abstract::Type 3 von Willebrand disease, a recessive autosomally inherited bleeding disorder, refers to complete deficiency of von Willebrand factor (VWF). The novel Q1311X mutation was detected in the homozygous state in four Spanish patients from two apparently unrelated families of gypsy origin. The lack of specific amplific...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.02410.x
更新日期:2000-11-01 00:00:00
abstract::Four unrelated patients with a bleeding diathesis (bleeding time longer than 30 min), some spontaneous platelet aggregation, thrombocytopenia and large platelets, had decreased levels of factor VIII-von Willebrand factor (FVIII-VWF) related properties and impaired platelet adherence to human artery subendothelium. The...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1985.tb07333.x
更新日期:1985-03-01 00:00:00