Abstract:
:Although tyrosine kinase inhibitors have redefined the care of chronic myeloid leukemia (CML), these agents have not proved curative, likely due to resistance of the leukemia stem cells (LSC). While a number of potential therapeutic targets have emerged in CML, their expression in the LSC remains largely unknown. We therefore isolated subsets of CD34(+) stem/progenitor cells from normal donors and from patients with chronic phase or blast crisis CML. These cell subsets were then characterized based on ability to engraft immunodeficient mice and expression of candidate therapeutic targets. The CD34(+)CD38(-) CML cell population with high aldehyde dehydrogenase (ALDH) activity was the most enriched for immunodeficient mouse engrafting capacity. The putative targets: PROTEINASE 3, SURVIVIN, and hTERT were expressed only at relatively low levels by the CD34(+)CD38(-)ALDH(high) CML cells, similar to the normal CD34(+)CD38(-)ALDH(high) cells and less than in the total CML CD34(+) cells. In fact, the highest expression of these antigens was in normal, unfractionated CD34(+) cells. In contrast, PRAME and WT1 were more highly expressed by all CML CD34(+) subsets than their normal counterparts. Thus, ALDH activity appears to enrich for CML stem cells, which display an expression profile that is distinct from normal stem/progenitor cells and even the CML progenitors. Indeed, expression of a putative target by the total CD34(+) population in CML does not guarantee expression by the LSC. These expression patterns suggest that PROTEINASE 3, SURVIVIN, and hTERT are not optimal therapeutic targets in CML stem cells; whereas PRAME and WT1 seem promising.
journal_name
Am J Hematoljournal_title
American journal of hematologyauthors
Gerber JM,Qin L,Kowalski J,Smith BD,Griffin CA,Vala MS,Collector MI,Perkins B,Zahurak M,Matsui W,Gocke CD,Sharkis SJ,Levitsky HI,Jones RJdoi
10.1002/ajh.21915subject
Has Abstractpub_date
2011-01-01 00:00:00pages
31-7issue
1eissn
0361-8609issn
1096-8652journal_volume
86pub_type
杂志文章abstract::Autologous stem cell transplantation (ASCT) is feasible and effective in selected older patients with Multiple Myeloma, but specific criteria for evaluating ASCT eligibility in elderly patients are lacking. We evaluated 131 patients aged 65-75 considered for ASCT at our center: The Charlson Comorbidity Index (CCI), He...
journal_title:American journal of hematology
pub_type: 临床试验,杂志文章
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abstract::The expression of CD45 RA/RO antigen was investigated in neoplasms including cases expressing CD7 antigen as the sole pan-T antigen (n = 8), T-lineage acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL) at various stages of differentiation (n = 32), peripheral stage T-lineage leukemia (n = 10) and adult T-...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830490103
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pub_type: 杂志文章,多中心研究
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journal_title:American journal of hematology
pub_type: 杂志文章
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更新日期:2015-04-01 00:00:00
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journal_title:American journal of hematology
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journal_title:American journal of hematology
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2015-06-01 00:00:00
abstract::Clopidogrel is a widely used antiplatelet agent that irreversibly inhibits platelet P2Y12 ADP receptors after conversion to an active metabolite. There are a number of laboratory tests capable of detecting clopidogrel-induced platelet inhibition and published literature correlates suboptimal clopidogrel response to ad...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
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journal_title:American journal of hematology
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更新日期:1987-05-01 00:00:00
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journal_title:American journal of hematology
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journal_title:American journal of hematology
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更新日期:1987-07-01 00:00:00
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journal_title:American journal of hematology
pub_type: 临床试验,杂志文章
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更新日期:2013-02-01 00:00:00
abstract::New treatments have transformed multiple myeloma into a chronic disease. Hence, optimal management of treatment and disease-related complications remains a critical component of survivorship care. Survivorship care model in cancers requiring a fixed-duration therapy may not be applicable to myeloma, since patients are...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
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abstract::Heparin-induced thrombocytopenia is a rare but severe complication of heparin therapy that can result in severe venous or arterial thromboembolic events and whose treatment remains partially unanswered. Recombinant hirudin is potentially effective as an antithrombotic treatment in the management of heparin-induced thr...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830500105
更新日期:1995-09-01 00:00:00
abstract::Levels of many coagulation factors are low in the healthy infant and even lower in the asphyxiated premature infant. We investigated whether a brief exposure to asphyxia at the time of birth causes the activation and consumption of coagulation factors. Following delivery by caesarean section, premature lambs were asph...
journal_title:American journal of hematology
pub_type: 杂志文章
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更新日期:1988-07-01 00:00:00
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journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830340316
更新日期:1990-07-01 00:00:00
abstract::The authors report a 10-year-old boy with hepatosplenic gammadelta T-cell lymphoma, a rare form of lymphoma that is highly aggressive, exceedingly rare in children, and primarily seen in young men. Conventional multi-agent chemotherapy appears to be inadequate for cure. This is the first report with this type of lymph...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.10466
更新日期:2004-02-01 00:00:00
abstract::Acquired pure megakaryocytic aplasia is a rare disorder defined by severe thrombocytopenia with no other hematologic abnormalities and absent, or severely decreased marrow megakaryocytes. The etiology may be immune suppression of megakaryocyte development. Two patients are described who both responded rapidly to a com...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(sici)1096-8652(199910)62:2<115::aid-ajh10
更新日期:1999-10-01 00:00:00
abstract::Induction of carbonic anhydrase isozyme I (CA-I) by erythropoietin or hemin was investigated using erythroleukemia (K562) cells. Immunological estimation and purification of carbonic anhydrases showed that untreated K562 cells contained only carbonic anhydrase isozyme II(CA-II), while incubation of the cells with 2 un...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830380309
更新日期:1991-11-01 00:00:00
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journal_title:American journal of hematology
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更新日期:2000-03-01 00:00:00
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journal_title:American journal of hematology
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更新日期:1995-10-01 00:00:00
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journal_title:American journal of hematology
pub_type: 杂志文章
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更新日期:1991-03-01 00:00:00
abstract::A 74-year old woman with Ph1-negative chronic myelogenous leukemia (CML) and heterozygous for glucose-6-phosphate dehydrogenase (G6PD) was studied. Both A and B types of G6PD were found in skin. In contrast, white blood cells and platelets showed only a single G6PD type A. These results provide further evidence that P...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830170113
更新日期:1984-07-01 00:00:00
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journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830350406
更新日期:1990-12-01 00:00:00
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journal_title:American journal of hematology
pub_type: 杂志文章,多中心研究
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更新日期:2016-07-01 00:00:00
abstract::If a translocation is followed by loss of one of the two derivative chromosomes, the result is an unbalanced translocation, showing monosomy for the segments making up the lost derivative. We have found that in most unbalanced translocations, a third event takes place: a morphologically normal copy of one of the two t...
journal_title:American journal of hematology
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journal_title:American journal of hematology
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更新日期:2006-11-01 00:00:00
abstract::We describe a unique case of adult T-cell leukemia/lymphoma (ATL). The patient had typical clinicohematological features as ATL, but showed a lack of antibody to human T-cell leukemia virus type-1 (HTLV-1) and was negative for HTLV-1 proviral DNA in the peripheral mononuclear cells by means of polymerase chain reactio...
journal_title:American journal of hematology
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doi:10.1002/(sici)1096-8652(200005)64:1<64::aid-ajh11>
更新日期:2000-05-01 00:00:00
abstract:DISEASE OVERVIEW:Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, h...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
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更新日期:2020-07-01 00:00:00
abstract::Sickle (Hb SS) red cells, preloaded with 45Ca by reversal of hemolysis, exhibit an incomplete 45Ca extrusion, retaining approximately four times more 45Ca than normal cells. Studies indicated that neither the reduction in Hb SS cell Ca2+-Mg2+ ATPase activity (84% of normal) nor the activation of Ca2+-Mg2+ ATPase by ca...
journal_title:American journal of hematology
pub_type: 杂志文章
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更新日期:1980-01-01 00:00:00