Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia.


:Deregulation of signal transduction pathways (STPs) may promote leukemogenesis by conferring cell proliferation and survival advantages in acute myelogenous leukemia (AML). Several agents targeting STPs are under development; however, redundancy and cross-talk between STPs could activate multiple downstream effectors and this could negate the effect of single-target inhibition. The frequency of concurrent activation of multiple STPs in AML and the prognostic relevance of STP activation in AML are unknown. STP protein expression (PKCalpha, ERK2, pERK2, AKT, and pAKT) was measured by Western blot in samples from 188 patients with newly diagnosed, untreated AML. In univariate and multivariate analysis high levels of PKCalpha, ERK, pERK, and pAKT, but not AKT, were adverse factors for survival as was the combination variable PKCalpha-ERK2&pERK2-pAKT. Survival progressively decreased as the number of activated pathways increased. Patients were more likely to have none or all 3 pathways activated than was predicted based on the frequency of individual pathway activation, strongly suggesting that cross-activation occurred. Simultaneous activation of multiple STPs is common in AML and has a progressively worse adverse effect on prognosis. It is thus likely that only combinations of agents that target the multiply activated STPs will be beneficial for patients with AML.






Kornblau SM,Womble M,Qiu YH,Jackson CE,Chen W,Konopleva M,Estey EH,Andreeff M




Has Abstract


2006-10-01 00:00:00
















  • Frequency and severity of central nervous system lesions in hemophagocytic lymphohistiocytosis.

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    pub_type: 杂志文章


    authors: Haddad E,Sulis ML,Jabado N,Blanche S,Fischer A,Tardieu M

    更新日期:1997-02-01 00:00:00

  • Defective polymorphonuclear leukocyte metabolism and function in canine cyclic neutropenia.

    abstract::Humans and grey collie dogs with cyclic neutropenia are known to suffer from an increased rate of bacterial infection. Because of the previously described microanatomic abnormalities of lysosome formation found in the polymorphonuclear leukocytes (PMNs) of dogs with canine cyclic neutropenia, studies of these cells we...


    pub_type: 杂志文章


    authors: Chusid MJ,Bujak JS,Dale DC

    更新日期:1975-12-01 00:00:00

  • Thrombopoietin, but not erythropoietin, directly stimulates multilineage growth of primitive murine bone marrow progenitor cells in synergy with early acting cytokines: distinct interactions with the ligands for c-kit and FLT3.

    abstract::Thrombopoietin (Tpo), the ligand for c-mpl, has been shown to be the principal regulator of megakaryocytopoiesis and platelet production. The ability of Tpo to potently stimulate the growth of committed megakaryocyte (Mk) progenitor cells has been studied in detail. Murine fetal liver cells, highly enriched in primiti...


    pub_type: 杂志文章


    authors: Ramsfjell V,Borge OJ,Veiby OP,Cardier J,Murphy MJ Jr,Lyman SD,Lok S,Jacobsen SE

    更新日期:1996-12-15 00:00:00

  • Adaptive response of iron absorption to anemia, increased erythropoiesis, iron deficiency, and iron loading in beta2-microglobulin knockout mice.

    abstract::Recently, a novel gene of the major histocompatibility complex (MHC) class I family, HFE (HLA-H), has been found to be mutated in a large proportion of hereditary hemochromatosis (HH) patients. Further support for a causative role of HFE in this disease comes from the observation that beta2-microglobulin knockout (bet...


    pub_type: 杂志文章


    authors: Santos M,Clevers H,de Sousa M,Marx JJ

    更新日期:1998-04-15 00:00:00

  • Hemophagocytic lymphohistiocytosis is associated with deficiencies of cellular cytolysis but normal expression of transcripts relevant to killer-cell-induced apoptosis.

    abstract::In 65 patients with hemophagocytic lymphohistiocytosis (HLH), we found an as yet undescribed heterogeneity of defects in cellular cytotoxicity when assay conditions were modified by the incubation time, the presence of mitogen, or interleukin-2 (IL-2). The standard 4-hour natural killer (NK) test against K562 targets ...


    pub_type: 杂志文章


    authors: Schneider EM,Lorenz I,Müller-Rosenberger M,Steinbach G,Kron M,Janka-Schaub GE

    更新日期:2002-10-15 00:00:00

  • Prevalence of heterozygotes for hemochromatosis in the white population of the United States.

    abstract::In previous studies, the prevalence of HLA-linked hemochromatosis, thought to be the most common genetic illness in whites, has been estimated by identifying homozygotes in the population. Because not all homozygotes express the disease phenotypically, the accuracy of these estimates is uncertain. We analyzed the dist...


    pub_type: 杂志文章


    authors: McLaren CE,Gordeuk VR,Looker AC,Hasselblad V,Edwards CQ,Griffen LM,Kushner JP,Brittenham GM

    更新日期:1995-09-01 00:00:00

  • Interleukin-7 is produced by afferent lymphatic vessels and supports lymphatic drainage.

    abstract::The cytokine interleukin (IL)-7 exerts essential roles in lymph node (LN) organogenesis and lymphocyte development and homeostasis. Recent studies have identified lymphatic endothelial cells (LECs) as a major source of IL-7 in LNs. Here, we report that LECs not only produce IL-7, but also express the IL-7 receptor cha...


    pub_type: 杂志文章


    authors: Iolyeva M,Aebischer D,Proulx ST,Willrodt AH,Ecoiffier T,Häner S,Bouchaud G,Krieg C,Onder L,Ludewig B,Santambrogio L,Boyman O,Chen L,Finke D,Halin C

    更新日期:2013-09-26 00:00:00

  • Vascular endothelial growth factor-A induces plaque expansion in ApoE knock-out mice by promoting de novo leukocyte recruitment.

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    pub_type: 杂志文章


    authors: Lucerna M,Zernecke A,de Nooijer R,de Jager SC,Bot I,van der Lans C,Kholova I,Liehn EA,van Berkel TJ,Yla-Herttuala S,Weber C,Biessen EA

    更新日期:2007-01-01 00:00:00

  • Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study.

    abstract::Between 1990 and 1996, we conducted a randomized trial in adults with newly diagnosed acute myeloid leukemia (AML) in order to compare relapse-free interval (RFI) after double induction (arm B), timed-sequential induction (arm C), or control "3 + 7" induction (arm A). Patients achieving complete remission (CR) after i...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Castaigne S,Chevret S,Archimbaud E,Fenaux P,Bordessoule D,Tilly H,de Revel T,Simon M,Dupriez B,Renoux M,Janvier M,Micléa JM,Thomas X,Bastard C,Preudhomme C,Bauters F,Degos L,Dombret H

    更新日期:2004-10-15 00:00:00

  • The nonexpression of CD36 on reticulocytes and mature red blood cells does not modify the clinical course of patients with sickle cell anemia.

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    pub_type: 杂志文章


    authors: Lee K,Gane P,Roudot-Thoraval F,Godeau B,Bachir D,Bernaudin F,Cartron JP,Galactéros F,Bierling P

    更新日期:2001-08-15 00:00:00

  • The hematopoietic stem cell niche in homeostasis and disease.

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    pub_type: 杂志文章,评审


    authors: Calvi LM,Link DC

    更新日期:2015-11-26 00:00:00

  • A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders.

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    pub_type: 杂志文章


    authors: Simeoni I,Stephens JC,Hu F,Deevi SV,Megy K,Bariana TK,Lentaigne C,Schulman S,Sivapalaratnam S,Vries MJ,Westbury SK,Greene D,Papadia S,Alessi MC,Attwood AP,Ballmaier M,Baynam G,Bermejo E,Bertoli M,Bray PF,Bury L,

    更新日期:2016-06-09 00:00:00

  • Bispecific and split CAR T cells targeting CD13 and TIM3 eradicate acute myeloid leukemia.

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    pub_type: 杂志文章


    authors: He X,Feng Z,Ma J,Ling S,Cao Y,Gurung B,Wu Y,Katona BW,O'Dwyer KP,Siegel DL,June CH,Hua X

    更新日期:2020-03-05 00:00:00

  • Accumulation of HIF-1alpha under the influence of nitric oxide.

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    pub_type: 杂志文章


    authors: Sandau KB,Fandrey J,Brüne B

    更新日期:2001-02-15 00:00:00

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    authors: Rettinger E,Willasch AM,Kreyenberg H,Borkhardt A,Holter W,Kremens B,Strahm B,Woessmann W,Mauz-Koerholz C,Gruhn B,Burdach S,Albert MH,Schlegel PG,Klingebiel T,Bader P

    更新日期:2011-11-17 00:00:00

  • Initial bone marrow reticulin fibrosis in polycythemia vera exerts an impact on clinical outcome.

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    pub_type: 杂志文章,多中心研究


    authors: Barbui T,Thiele J,Passamonti F,Rumi E,Boveri E,Randi ML,Bertozzi I,Marino F,Vannucchi AM,Pieri L,Rotunno G,Gisslinger H,Gisslinger B,Müllauer L,Finazzi G,Carobbio A,Gianatti A,Ruggeri M,Nichele I,D'Amore E,Rambald

    更新日期:2012-03-08 00:00:00

  • Multiple myeloma.

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    pub_type: 历史文章,杂志文章,评审


    authors: Kyle RA,Rajkumar SV

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  • NHERF-2 silences the silencers.

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    pub_type: 评论,杂志文章


    authors: Arbiser JL

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  • Impaired interleukin-3 response in Pim-1-deficient bone marrow-derived mast cells.

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    authors: Domen J,van der Lugt NM,Laird PW,Saris CJ,Clarke AR,Hooper ML,Berns A

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  • Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and Pediatric Disea

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    pub_type: 临床试验,杂志文章,多中心研究


    authors: Klingebiel T,Cornish J,Labopin M,Locatelli F,Darbyshire P,Handgretinger R,Balduzzi A,Owoc-Lempach J,Fagioli F,Or R,Peters C,Aversa F,Polge E,Dini G,Rocha V,Pediatric Diseases and Acute Leukemia Working Parties of the Europe

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  • Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI.

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    pub_type: 杂志文章


    authors: Brondijk TH,de Ruiter T,Ballering J,Wienk H,Lebbink RJ,van Ingen H,Boelens R,Farndale RW,Meyaard L,Huizinga EG

    更新日期:2010-02-18 00:00:00

  • The third-generation bisphosphonate zoledronate synergistically augments the anti-Ph+ leukemia activity of imatinib mesylate.

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    pub_type: 杂志文章


    authors: Kuroda J,Kimura S,Segawa H,Kobayashi Y,Yoshikawa T,Urasaki Y,Ueda T,Enjo F,Tokuda H,Ottmann OG,Maekawa T

    更新日期:2003-09-15 00:00:00

  • Human skin-derived mast cells can proliferate while retaining their characteristic functional and protease phenotypes.

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    pub_type: 杂志文章


    authors: Kambe N,Kambe M,Kochan JP,Schwartz LB

    更新日期:2001-04-01 00:00:00

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    pub_type: 杂志文章


    authors: Lew VL,Daw N,Perdomo D,Etzion Z,Bookchin RM,Tiffert T

    更新日期:2003-12-01 00:00:00

  • Ameliorating effects of fluorocarbon emulsion on sickle red blood cell-induced obstruction in an ex vivo vasculature.

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    pub_type: 杂志文章


    authors: Kaul DK,Liu X,Nagel RL

    更新日期:2001-11-15 00:00:00

  • Diferric transferrin regulates transferrin receptor 2 protein stability.

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    pub_type: 杂志文章


    authors: Johnson MB,Enns CA

    更新日期:2004-12-15 00:00:00

  • Interleukin-2 may induce prolonged remissions in advanced acute myelogenous leukemia.

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    pub_type: 临床试验,杂志文章


    authors: Meloni G,Foa R,Vignetti M,Guarini A,Fenu S,Tosti S,Tos AG,Mandelli F

    更新日期:1994-10-01 00:00:00

  • Positive and negative regulation of granulocyte-macrophage colony-stimulating factor promoter activity by AML1-related transcription factor, PEBP2.

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    pub_type: 杂志文章


    authors: Takahashi A,Satake M,Yamaguchi-Iwai Y,Bae SC,Lu J,Maruyama M,Zhang YW,Oka H,Arai N,Arai K

    更新日期:1995-07-15 00:00:00

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    pub_type: 杂志文章


    authors: Steinmann C,Reber P,Jungo M,Lämmle B,Heinemann G,Wermuth B,Furlan M

    更新日期:1993-10-01 00:00:00

  • Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity.

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    pub_type: 临床试验,杂志文章


    authors: Mathews V,George B,Lakshmi KM,Viswabandya A,Bajel A,Balasubramanian P,Shaji RV,Srivastava VM,Srivastava A,Chandy M

    更新日期:2006-04-01 00:00:00