Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia.

Abstract:

:Natural killer (NK) cells are the first lymphocytes to recover after allogeneic stem cell transplantation (SCT) and can exert powerful graft-versus-leukemia (GVL) effects determining transplant outcome. Conditions governing NK cell alloreactivity and the role of NK recovery in sibling SCT are not well defined. NK cells on day 30 post-transplant (NK30) were measured in 54 SCT recipients with leukemia and donor and recipient killer immunoglobulin-like receptor (KIR) genotype determined. In univariate analysis, donor KIR genes 2DL5A, 2DS1, 3DS1 (positive in 46%) and higher numbers of inhibitory donor KIR correlated with higher NK30 counts and were associated with improved transplant outcome. NK30 counts also correlated directly with the transplant CD34 cell dose and inversely with the CD3+ cell dose. In multivariate analysis, the NK30 emerged as the single independent determinant of transplant outcome. Patients with NK30 >150/microl had less relapse (HR 18.3, P=0.039), acute graft-versus-host disease (HR 3.2, P=0.03), non-relapse mortality (HR 10.7, P=0.028) and improved survival (HR 11.4, P=0.03). Results suggest that T cell-depleted SCT might be improved and the GVL effect enhanced by selecting donors with favorable KIR genotype, and by optimizing CD34 and CD3 doses.

journal_name

Leukemia

journal_title

Leukemia

authors

Savani BN,Mielke S,Adams S,Uribe M,Rezvani K,Yong AS,Zeilah J,Kurlander R,Srinivasan R,Childs R,Hensel N,Barrett AJ

doi

10.1038/sj.leu.2404892

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

2145-52

issue

10

eissn

0887-6924

issn

1476-5551

pii

2404892

journal_volume

21

pub_type

杂志文章

相关文献

LEUKEMIA文献大全
  • Telomere length identifies two different prognostic subgroups among VH-unmutated B-cell chronic lymphocytic leukemia patients.

    abstract::Some evidences suggest that telomere restriction fragment length (TRF-L) is an effective indicator of histopathogenesis in B-cell tumors. As histopathogenesis is relevant for B-cell chronic lymphocytic leukemia (B-CLL) prognosis, TRF-L was assessed by Southern blot in 201 patients and compared to variable immunoglobul...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2404544

    authors: Ricca I,Rocci A,Drandi D,Francese R,Compagno M,Lobetti Bodoni C,De Marco F,Astolfi M,Monitillo L,Vallet S,Calvi R,Ficara F,Omedè P,Rosato R,Gallamini A,Marinone C,Bergui L,Boccadoro M,Tarella C,Ladetto M

    更新日期:2007-04-01 00:00:00

  • Phase I/II study of gemtuzumab ozogamicin added to fludarabine, melphalan and allogeneic hematopoietic stem cell transplantation for high-risk CD33 positive myeloid leukemias and myelodysplastic syndrome.

    abstract::We investigated the hypothesis that gemtuzumab ozogamicin (GO), an anti-CD33 immunotoxin would improve the efficacy of fludarabine/melphalan as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/II trial. Toxicity was defined as grades III-IV organ damage, engraftment fail...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2405014

    authors: de Lima M,Champlin RE,Thall PF,Wang X,Martin TG 3rd,Cook JD,McCormick G,Qazilbash M,Kebriaei P,Couriel D,Shpall EJ,Khouri I,Anderlini P,Hosing C,Chan KW,Andersson BS,Patah PA,Caldera Z,Jabbour E,Giralt S

    更新日期:2008-02-01 00:00:00

  • Karyotypic patterns in chronic myeloproliferative disorders: report on 74 cases and review of the literature.

    abstract::During the 15 year period 1975-1989, 74 cases of chronic myeloproliferative disorder (CMPD) were cytogenetically analyzed in our department. Thirty patients had polycythemia vera (PV), 23 had idiopathic myelofibrosis (MFS), 15 had idiopathic thrombocythemia (IT), and six had unclassifiable CMPD (UCMPD). The overall fr...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:

    authors: Mertens F,Johansson B,Heim S,Kristoffersson U,Mitelman F

    更新日期:1991-03-01 00:00:00

  • Absence of amplification of MDM2 gene, a regulator of p53 function, in myelodysplastic syndromes.

    abstract::The MDM2 gene is a gene whose product binds to p53 and regulates its function. Amplification of MDM2 has been found in human sarcomas, where it leads to inactivation of p53. In 64 cases of generally advanced myelodysplastic syndromes, we found no amplification or rearrangement of MDM2 gene by Southern analysis. MDM2 R...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Preudhomme C,Quesnel B,Vachee A,Lepelley P,Collyn-D'Hooghe M,Wattel E,Fenaux P

    更新日期:1993-08-01 00:00:00

  • Infantile leukemia and soybeans--a hypothesis.

    abstract::Recent molecular-genetic studies have revealed that in the majority of patients with secondary leukemia induced by topoisomerase II (topo II) inhibitors and also with infantile acute leukemia (IAL), the breakpoints are clustered within scaffold attachment regions (SARs) of 3'-MLL-bcr near exon 9. Genistein, abundant i...

    journal_title:Leukemia

    pub_type: 社论

    doi:10.1038/sj.leu.2401344

    authors: Abe T

    更新日期:1999-03-01 00:00:00

  • Clonality studies in acute myeloid leukemia.

    abstract::The study of X-chromosome inactivation patterns (XCIPs) to determine tumor clonality was established by Fialkow using G6PD protein isoenzymes but was limited by the low frequency of heterozygotes. Analysis was extended to most females with the demonstration of differential DNA methylation patterns on active and inacti...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/sj.leu.2400935

    authors: Gale RE,Linch DC

    更新日期:1998-02-01 00:00:00

  • Spontaneous responsiveness to cytokines by human T-cell leukemias.

    abstract::The molecular basis for autonomous growth of malignant forms of human T lymphocytes is not known. It can be investigated by functional responses of malignant cells in comparison with untransformed counterparts. At least two pathways (the CD2 and CD3 pathways) of human T-cell activation have been recently defined on th...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Schirren CA,Völpel H,Meuer SC

    更新日期:1992-06-01 00:00:00

  • Allogeneic stem cell transplantation for advanced acute promyelocytic leukemia: results in patients treated in second molecular remission or with molecularly persistent disease.

    abstract::In all, 17 consecutive patients in hematological complete remission (HCR) of acute promyelocytic leukemia (APL) received allogeneic stem cell transplantation (SCT) from an HLA-identical sibling and were monitored by reverse transcriptase polymerase chain reaction of PML/RARalpha prior and after transplant. Median age ...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2403078

    authors: Lo-Coco F,Romano A,Mengarelli A,Diverio D,Iori AP,Moleti ML,De Santis S,Cerretti R,Mandelli F,Arcese W

    更新日期:2003-10-01 00:00:00

  • Action of interferons in hairy cell leukemia.

    abstract::We have investigated the direct effects of interferon (IFN) on hairy cells (HCs) isolated from patients with hairy cell leukemia using one- and two-dimensional gel electrophoresis. We have previously characterized the induction of synthesis of 10-16 specific proteins by IFN-alpha 2b in HCs, as analyzed by one-dimensio...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Samuels BL,Rosner MC,Giometti CS,Golomb HM,Brownstein BH

    更新日期:1987-04-01 00:00:00

  • Cancer procoagulant in the human promyelocytic cell line NB4 and its modulation by all-trans-retinoic acid.

    abstract::Acute promyelocytic leukemia (APL) cells express different types of procoagulant activity (PCA), including tissue factor (TF), and cancer procoagulant (CP). The aim of this study was to investigate whether the NB4 cell line, the first ever isolated human APL line, with the typical t(15;17) chromosomal balance transloc...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Falanga A,Consonni R,Marchetti M,Mielicki WP,Rambaldi A,Lanotte M,Gordon SG,Barbui T

    更新日期:1994-01-01 00:00:00

  • Interstitial telomere repeats in translocations of hematopoietic disorders.

    abstract::Cytogenetic and fluorescence in situ hybridization studies have shown the presence of telomeric repeats in translocation present in three patients with hematopoietic malignancies. One had jumping translocations, involving 1q12 and 2q, 16p, and 19q. These sequences were detected by FISH only in derivative chromosomes t...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2401876

    authors: Busson Le Coniat M,Brizard F,Smadja NV,Maarek O,Der Sarkissian H,Berger R

    更新日期:2000-09-01 00:00:00

  • HTLV-I Tax trans-activation and cell growth signaling.

    abstract::We have cloned two genes for cell surface molecules, capable of delivering the intracellular signals, which are modulated for their expression by Tax. One is the gamma chain of the interleukin-2 (IL-2) receptor which is suggested to be critical for IL-2-dependent growth of human T-cell leukemia virus type I (HTLV-I) i...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Nakamura M,Takasawa N,Ohbo K,Higashimura N,Ohtani K,Tanaka Y,Sugamura K

    更新日期:1997-04-01 00:00:00

  • Refined cytogenetic-risk categorization for overall and leukemia-free survival in primary myelofibrosis: a single center study of 433 patients.

    abstract::We have previously identified sole +9, 13q- or 20q-, as 'favorable' and sole +8 or complex karyotype as 'unfavorable' cytogenetic abnormalities in primary myelofibrosis (PMF). In this study of 433 PMF patients, we describe additional sole abnormalities with favorable (chromosome 1 translocations/duplications) or unfav...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2010.234

    authors: Caramazza D,Begna KH,Gangat N,Vaidya R,Siragusa S,Van Dyke DL,Hanson C,Pardanani A,Tefferi A

    更新日期:2011-01-01 00:00:00

  • Inhibition of human leukemia in an animal model with human antibodies directed against vascular endothelial growth factor receptor 2. Correlation between antibody affinity and biological activity.

    abstract::Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) have been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis. We recently showed that certain 'liquid' tumors such as leukemia not only produce VEGF, but also express functional VEGFR, resulting in ...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2402831

    authors: Zhu Z,Hattori K,Zhang H,Jimenez X,Ludwig DL,Dias S,Kussie P,Koo H,Kim HJ,Lu D,Liu M,Tejada R,Friedrich M,Bohlen P,Witte L,Rafii S

    更新日期:2003-03-01 00:00:00

  • Targeting nuclear β-catenin as therapy for post-myeloproliferative neoplasm secondary AML.

    abstract::Transformation of post-myeloproliferative neoplasms into secondary (s) AML exhibit poor clinical outcome. In addition to increased JAK-STAT and PI3K-AKT signaling, post-MPN sAML blast progenitor cells (BPCs) demonstrate increased nuclear β-catenin levels and TCF7L2 (TCF4) transcriptional activity. Knockdown of β-caten...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/s41375-018-0334-3

    authors: Saenz DT,Fiskus W,Manshouri T,Mill CP,Qian Y,Raina K,Rajapakshe K,Coarfa C,Soldi R,Bose P,Borthakur G,Kadia TM,Khoury JD,Masarova L,Nowak AJ,Sun B,Saenz DN,Kornblau SM,Horrigan S,Sharma S,Qiu P,Crews CM,Versto

    更新日期:2019-06-01 00:00:00

  • Pomalidomide, bortezomib and low-dose dexamethasone in lenalidomide-refractory and proteasome inhibitor-exposed myeloma.

    abstract::This phase 1 dose-escalation study evaluated pomalidomide, bortezomib (subcutaneous (SC) or intravenous (IV)) and low-dose dexamethasone (LoDEX) in lenalidomide-refractory and proteasome inhibitor-exposed relapsed or relapsed and refractory multiple myeloma (RRMM). In 21-day cycles, patients received pomalidomide (1-4...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2017.173

    authors: Richardson PG,Hofmeister CC,Raje NS,Siegel DS,Lonial S,Laubach J,Efebera YA,Vesole DH,Nooka AK,Rosenblatt J,Doss D,Zaki MH,Bensmaine A,Herring J,Li Y,Watkins L,Chen MS,Anderson KC

    更新日期:2017-12-01 00:00:00

  • Integrin distribution and cytoskeleton organization in normal and malignant monocytes.

    abstract::In this work we have mapped by double-label immunofluorescence the cellular distribution of integrins and their relationship with cytoskeletal proteins in normal and malignant monocytes. In normal monocytes, CD18 and CD11c are concentrated at specific adhesion sites, named podosomes, together with actin, vinculin, and...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Gaidano G,Bergui L,Schena M,Gaboli M,Cremona O,Marchisio PC,Caligaris-Cappio F

    更新日期:1990-10-01 00:00:00

  • Mesenchymal stem cells in suppression or progression of hematologic malignancy: current status and challenges.

    abstract::Mesenchymal stem cells (MSCs) are known for being multi-potent. However, they also possess anticancer properties, which has prompted efforts to adapt MSCs for anticancer therapies. However, MSCs have also been widely implicated in pathways that contribute to tumor growth. Numerous studies have been conducted to adapt ...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/s41375-018-0373-9

    authors: Lee MW,Ryu S,Kim DS,Lee JW,Sung KW,Koo HH,Yoo KH

    更新日期:2019-03-01 00:00:00

  • Results of the randomized phase IIB ADMIRE trial of FCR with or without mitoxantrone in previously untreated CLL.

    abstract::ADMIRE was a multicenter, randomized-controlled, open, phase IIB superiority trial in previously untreated chronic lymphocytic leukemia. Conventional front-line therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). Initial evidence from non-randomized phase II trials suggested that the addition...

    journal_title:Leukemia

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1038/leu.2017.65

    authors: Munir T,Howard DR,McParland L,Pocock C,Rawstron AC,Hockaday A,Varghese A,Hamblin M,Bloor A,Pettitt A,Fegan C,Blundell J,Gribben JG,Phillips D,Hillmen P

    更新日期:2017-10-01 00:00:00

  • Dasatinib vs. imatinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) who have not achieved an optimal response to 3 months of imatinib therapy: the DASCERN randomized study.

    abstract::Early molecular response is associated with improved probability of deep molecular response and superior survival in patients with CML-CP. However, ~1 in 3 patients on first-line imatinib do not achieve this threshold. The phase 2b DASCERN trial (NCT01593254) assessed the outcome of early switch to dasatinib in patien...

    journal_title:Leukemia

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1038/s41375-020-0805-1

    authors: Cortes JE,Jiang Q,Wang J,Weng J,Zhu H,Liu X,Hochhaus A,Kim DW,Radich J,Savona M,Martin-Regueira P,Sy O,Gurnani R,Saglio G

    更新日期:2020-08-01 00:00:00

  • Chromatin structure and transcriptional regulation of the stem cell leukaemia (SCL) gene in mast cells.

    abstract::The stem cell leukaemia (SCL) gene is a member of the basic helix-loop-helix family of transcription factors and is essential for the development of all haematopoietic lineages. SCL is expressed in pluripotent haematopoietic stem cells and also following commitment to the erythroid, mast and megakaryocytic lineages. T...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2401420

    authors: Fordham JL,Göttgens B,McLaughlin F,Green AR

    更新日期:1999-05-01 00:00:00

  • Alternative rearrangements of immunoglobulin light chain genes in human leukemia.

    abstract::Immunoglobulin heavy and light chain genes undergo rearrangement before they can be expressed by B-cells. A sequence of successive rearrangements has been proposed, suggesting that these events are initiated on heavy chain genes and are followed by sequential attempts of light chain gene rearrangements involving kappa...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Tang JQ,Béné MC,Faure GC

    更新日期:1991-08-01 00:00:00

  • Resistance to cytosine arabinoside in acute leukemia: the significance of mutations in CTP synthetase.

    abstract::The molecular events which confer cellular resistance to cytotoxic drugs such as cytosine arabinoside (ara-C) are poorly understood. Nevertheless, in a proportion of patients with acute leukemia, such events will be responsible for the failure of therapy. Mutations which cause ara-C resistance in a chinese hamster ova...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Whelan J,Smith T,Phear G,Rohatiner A,Lister A,Meuth M

    更新日期:1994-02-01 00:00:00

  • Galectin-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways.

    abstract::Galectins constitute a family of lectins that specifically exhibit the affinity for beta-galactosides and modulate various biological events. Galectin-9 is a tandem-repeat type galectin with two carbohydrate recognition domains and has recently been shown to have an anti-proliferative effect on cancer cells. We invest...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2010.25

    authors: Kobayashi T,Kuroda J,Ashihara E,Oomizu S,Terui Y,Taniyama A,Adachi S,Takagi T,Yamamoto M,Sasaki N,Horiike S,Hatake K,Yamauchi A,Hirashima M,Taniwaki M

    更新日期:2010-04-01 00:00:00

  • OCT1 and imatinib transport in CML: is it clinically relevant?

    abstract::Imatinib is a highly effective therapy for chronic phase-chronic myeloid leukaemia (CP-CML) patients; however, responses to frontline imatinib are variable. The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter involved in imatinib uptake into CML cells. Furthermore...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/leu.2015.170

    authors: Watkins DB,Hughes TP,White DL

    更新日期:2015-10-01 00:00:00

  • Two acute monocytic leukemia (AML-M5a) cell lines (MOLM-13 and MOLM-14) with interclonal phenotypic heterogeneity showing MLL-AF9 fusion resulting from an occult chromosome insertion, ins(11;9)(q23;p22p23).

    abstract::We describe two new human leukemia cell lines, MOLM-13 and MOLM-14, established from the peripheral blood of a patient at relapse of acute monocytic leukemia, FAB M5a, which had evolved from myelodysplastic syndrome (MDS). Both cell lines express monocyte-specific esterase (MSE) and MLL-AF9 fusion mRNA. Gene fusion is...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2400768

    authors: Matsuo Y,MacLeod RA,Uphoff CC,Drexler HG,Nishizaki C,Katayama Y,Kimura G,Fujii N,Omoto E,Harada M,Orita K

    更新日期:1997-09-01 00:00:00

  • Role of DNA methylation for expression of novel stem cell marker CDCP1 in hematopoietic cells.

    abstract::CDCP1, a novel stem cell marker, is expressed in hematopoietic cell line K562 but not in Jurkat. When CDCP1 promoter was transfected exogenously, Jurkat showed comparable promoter activity with K562, suggesting that the factor to enhance transcription was present but interfered to function in Jurkat. The reporter assa...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2404312

    authors: Kimura H,Morii E,Ikeda JI,Ezoe S,Xu JX,Nakamichi N,Tomita Y,Shibayama H,Kanakura Y,Aozasa K

    更新日期:2006-09-01 00:00:00

  • Revealing the role of TEL/AML1 for leukemic cell survival by RNAi-mediated silencing.

    abstract::Translocation (12;21), the most frequent chromosomal aberration in childhood acute lymphoblastic leukemia, creates TEL/AML1 fusion gene. Resulting hybrid protein was shown to have a role in pre-leukemia establishment. To address its role for leukemic cell survival, we applied RNA interference to silence TEL/AML1 in le...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2010.277

    authors: Zaliova M,Madzo J,Cario G,Trka J

    更新日期:2011-02-01 00:00:00

  • Regulation of IL-2 signaling.

    abstract::Several tyrosine kinases such as Jak1, Jak3, Lck and Syk are known to participate in IL-2-mediated intracellular signal transduction. Jak1, Lck and Syk are associated with the cytoplasmic domain of the beta chain, whereas Jak3 is associated with the cytoplasmic domain of the gamma chain, which is shared among receptor...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Higuchi M,Asao H,Tanaka N,Oda K,Takeshita T,Sugamura K

    更新日期:1997-04-01 00:00:00

  • A multiplex RT-PCR assay for the detection of chimeric transcripts encoded by the risk-stratifying translocations of pediatric acute lymphoblastic leukemia.

    abstract::Modern therapy for pediatric acute lymphoblastic leukemia (ALL) is based on the principle of risk stratification. One of the most important laboratory features used to accurately risk stratify patients is the presence of specific chromosomal translocation within the leukemic blasts. In this paper, we describe a multip...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2401224

    authors: Scurto P,Hsu Rocha M,Kane JR,Williams WK,Haney DM,Conn WP,Shurtleff SA,Downing JR

    更新日期:1998-12-01 00:00:00