Abstract:
:Chronic myeloid leukemia (CML) is caused by Bcr-Abl, a constitutively active tyrosine kinase that is the result of a reciprocal translocation between chromosomes 9 and 22 and cytogenetically evident as the Philadelphia chromosome. Imatinib (Glivec, Gleevec), a specific small molecule inhibitor of Bcr-Abl, has become the standard drug therapy for CML, and has dramatically diminished the use of allogeneic stem cell transplantation. Despite unprecedented rates of complete cytogenetic response, residual disease remains detectable in the majority of patients, suggesting that imatinib fails to eradicate leukemic stem cells. In this publication, the current perspectives for CML patients treated with imatinib are reviewed, focusing on the results of both standard and high-dose therapy. Monitoring of time-dependent prognostic factors is reviewed. The reasons imatinib may not be able to eradicate the disease are discussed, and potential strategies to achieve disease elimination are presented. Lastly, resistance to imatinib and the potential of second-generation Abl kinase inhibitors in the setting of clinical resistance are considered.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Deininger MWdoi
10.1016/j.exphem.2007.01.023subject
Has Abstractpub_date
2007-04-01 00:00:00pages
144-54issue
4 Suppl 1eissn
0301-472Xissn
1873-2399pii
S0301-472X(07)00026-4journal_volume
35pub_type
杂志文章,评审abstract::The cloning efficiency of T-lymphocyte progenitor cells (CFU-T) is dependent on mononuclear cell concentration, with a triphasic growth curve. At low plating cell concentrations, hydrocortisone causes a dose-dependent decrease in cloning efficiency, whereas at high cell concentrations hydrocortisone causes increased c...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-02-01 00:00:00
abstract:OBJECTIVE:Clonal stem cell proliferation and increased erythrocyte mass are hallmarks of the myeloproliferative disorder polycythemia vera (PV). The molecular basis of PV is unknown. METHODS:We carried out a genome-wide screening for loss of heterozygosity (LOH) and analyzed candidate genes within the LOH loci. RESUL...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00789-5
更新日期:2002-03-01 00:00:00
abstract::Growth and differentiation of hematopoietic stem cells occur in close contact with the cells and extracellular-matrix (ECM) proteins of the hematopoietic microenvironment. We observed the role of fibronectin, a matrix glycoprotein proposed to be involved in the attachment of hematopoietic cells and in the binding of s...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract:OBJECTIVE:New nonmyeloablative strategies to improve acceptance of mismatched bone marrow (BM) may compensate for the inadequate supply of compatible grafts. Recently we proposed to facilitate engraftment of mismatched BM by selective depletion of activated donor-reactive host cells with cyclophosphamide (CY). Here we ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.07.017
更新日期:2004-11-01 00:00:00
abstract:OBJECTIVE:Polycythemia vera (PV) is characterized by erythrocytosis associated with the presence of the activating JAK2(V617F) mutation in a variable proportion of hematopoietic cells. JAK2(V617F) is detected in other myeloproliferative neoplasms, does not appear to be the PV-initiating event, and its specific role in ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.09.009
更新日期:2009-12-01 00:00:00
abstract::Expression of the main nuclear protooncogenes during terminal megakaryocyte (MK) differentiation is poorly understood. Because previous results have suggested that c-fos and c-jun protooncogenes are expressed in human leukemic cell lines induced to undergo megakaryocytic differentiation, we have analyzed the expressio...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract:OBJECTIVE:Stem cell transplantation has a place in the management of many patients with hematological disorders, but is no longer the final and definitive treatment for most of these individuals. The relapsing patient may be offered further therapy, and evaluating the contribution of the treatments available has become...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.06.007
更新日期:2008-11-01 00:00:00
abstract::The effect on marrow myeloblast colony formation in blood from nine patients with acute myeloid leukemia was studied by using three recombinant-DNA-derived human leukocyte interferons (IFN alpha 2, IFN alpha-A, and IFN alpha-C). In preliminary experiments, a brief exposure of leukemic marrow cells to IFN alpha resulte...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-10-01 00:00:00
abstract:OBJECTIVE:The CD15 (Lewis x) cell surface oligosaccharide moiety is expressed in a variety of normal and tumor cells and recognized by selectins. The detection of CD15 on malignant Hodgkin-Reed-Sternberg (HRS) cells serves as a diagnostic marker of Hodgkin's lymphoma (HL). Retrospective studies suggest that the express...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00237-6
更新日期:2003-11-01 00:00:00
abstract::Both stimulatory (CSA) and inhibitory (INH) factors may contribute to hematopoietic regulation, but little is known about how their physiologic balance is maintained. Previously we have shown that antigen-defined fibroblastoid cells cultured from rat lung (ST3-/ST4+) constitutively produce INH, and those derived from ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::As neutropenia is a common side effect of treatment with 2-chlorodeoxyadenosine (2-CdA), we investigated the myelosuppressive action of 2-CdA in Dexter-type human long-term bone marrow cultures (LTBMCs). LTBMCs were incubated with varying doses of 2-CdA (5 to 20 nM/L) during the first week. At 20 and 10 nM/L 2-CdA, we...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract::Increasing evidence points to endoglin (Eng), an accessory receptor for the transforming growth factor-β superfamily commonly associated with the endothelial lineage, as an important regulator of the hematopoietic lineage. We have shown that lack of Eng results in reduced numbers of primitive erythroid colonies as wel...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2012.06.007
更新日期:2012-10-01 00:00:00
abstract:OBJECTIVE:It has been shown previously that infection with diverse viruses induces alterations in bone marrow lineage-specific progenitor cells. As complications arising from secondary bacterial infections can adversely affect the host, we investigated whether virally induced hematological alterations could contribute ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.09.005
更新日期:2005-12-01 00:00:00
abstract::Merocyanine 540 (MC 540) is a photosensitizing dye with antineoplastic and antiviral properties. Because photoexcited MC 540 generates singlet molecular oxygen and possibly other reactive oxygen species there is concern that MC 540-mediated photosensitization may be mutagenic. In this paper, we report on the induction...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-02-01 00:00:00
abstract:OBJECTIVE:We have previously shown that Flt3 ligand (FL)/Flt3 signaling regulates hematopoietic cell migration by modulating the SDF1alpha/CXCR4 signaling pathway. Herein, we evaluated whether a functional interaction between SDF1alpha/CXCR4 signaling and internal tandem duplication (ITD) of Flt3 regulates aberrant hem...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.04.001
更新日期:2006-08-01 00:00:00
abstract::We compared the kinetic recovery of lymphocytes and their subsets in two groups of patients submitted to allogeneic peripheral blood progenitor cell transplantation (allo-PBT): those receiving lymphocyte-depleted leukaphereses by positive selection of CD34+ cells (group 1, n = 18) and those receiving unmanipulated leu...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00029-0
更新日期:1999-03-01 00:00:00
abstract:OBJECTIVE:Based on previous animal experiments that suggest the plasticity of peripheral blood-derived, CD34(-) stem cell lines, the aim of this study was to isolate CD34(-) stem cell lines from human peripheral blood cells and obtain evidence of their multipotency and plasticity. MATERIALS AND METHODS:Adherent growin...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00865-2
更新日期:2002-08-01 00:00:00
abstract::The effects of the inhibition of the cyclooxygenase and lipoxygenase metabolic pathways of arachidonic acid on the postirradiation recovery of hematopoietic functions in mice were investigated. Nordihydroguaiaretic acid (NDGA), an inhibitor of prostaglandin (PG) and leukotriene (LT) production, was given to animals in...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::In the present study we investigated the absolute numbers of granulocytic progenitor cells (CFUc) in the spleens of adult normal dogs, their differentiation pattern and also their proliferative state. Between 10 and 40 times as many CFUc were found in the spleens of individual dogs as were present in the total blood v...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-09-01 00:00:00
abstract::To assess the thrombopoietic activity of erythropoietin (Epo) in vivo in mice, we consecutively administered recombinant human Epo (rEpo) i.p. to intact and splenectomized mice for varying time intervals. Recombinant human Epo increased platelet counts in a dose-dependent fashion in a short-term trial for 5 days. An 1...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1992-02-01 00:00:00
abstract::Early hematopoietic progenitor cells adhere to bone marrow stromal cells (BMSCs) mainly through VLA-4/VCAM-1 interactions. However, many adhesion molecules are expressed by these cell types. Cell adhesion molecules not only mediate adhesion; some are also capable of triggering cellular signaling events. These signals ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::The ability to epigenetically reprogram differentiated somatic cells to pluripotency resulting in the discovery of induced pluripotent stem cells (iPSCs), has unlocked fundamental biologic insights into numerous genetic diseases. These insights have resulted from the key property of iPSCs to differentiate into all cel...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2019.01.002
更新日期:2019-03-01 00:00:00
abstract::Interferon (INF)-α was the maintenance treatment of choice after autologous stem cell transplantation in multiple myeloma in the past, but currently Thalidomide is commonly used. In this prospective study, the implications of the various types of maintenance therapy on the patients T cell pattern and activation status...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2012.10.018
更新日期:2013-03-01 00:00:00
abstract::The processing of inflammatory signals occurs through a variety of mechanisms; the recent descriptions of the tethered ligand receptor for thrombin (JA Hoxie et al., J Biol Chem 268:13756, and TK Vu et al., Cell 64:1057) provide a novel route and mechanism for cellular activation after inflammation and thrombosis. Usi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract:OBJECTIVE:Polo-like kinase 1 (Plk1) is a regulator of the cell cycle that has been implicated in the pathology of many cancers. We have investigated whether this kinase plays a role in multiple myeloma (MM) using the Plk1 inhibitor BI 2536. MATERIALS AND METHODS:We have used six MM cell lines and six patient-derived s...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.12.006
更新日期:2011-03-01 00:00:00
abstract::Addition of carbamylcholine, a cholinergic analogue, to bone marrow cultures enhanced megakaryocytic and granulocytic growth by 60% and 42%, respectively. When carbamylcholine was added to spleen cells cultured in the presence of pokeweed mitogen, the resulting conditioned medium (PWM-SCM) increased the number of mega...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::An 18-year-old male with severe aplastic anemia associated with hepatitis was prepared for bone marrow transplantation with cyclophosphamide (50 mg/kg/day) for 4 consecutive days. He then received 3.47 X 10(8) nucleated bone marrow cells per kilogram of body weight from his HL-A identical sister by intravenous infusio...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-01-01 00:00:00
abstract::Cell surface molecules aberrantly expressed or overexpressed by myeloid leukemic cells represent potential disease-specific therapeutic targets for antibodies. MUC1 is a polymorphic glycoprotein, the cleavage of which yields two unequal chains: a large extracellular α subunit containing a tandem repeat array bound in ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2018.12.002
更新日期:2019-02-01 00:00:00
abstract::Rats made transiently neutropenic by intra-arterial administration of vinblastine (3 mg/kg) and infected with E. coli (6.02+/-0.45 X 10(8), per animal) have a mortality rate of 90% within 48 h post infection. Multiple transfusions of large numbers of granulocytes (harvested from Deca-Durabolin treated donor rats) prot...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
abstract:OBJECTIVE:B-lineage acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia in lymphatic blastic phase in adults have poor prognoses despite intensive chemotherapy. Novel targeted treatment modalities emerge, but their evaluation requires relevant in vitro models of lymphoblastic leukemia. Presently available c...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.11.002
更新日期:2009-03-01 00:00:00