Proteomic biomarkers of ALK+ lymphoma

ALK 淋巴瘤的蛋白质组生物标志物

基本信息

  • 批准号:
    7790983
  • 负责人:
  • 金额:
    $ 32.06万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-12-03 至 2013-11-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Anaplastic large-cell lymphoma (ALCL) is a distinct subtype of peripheral T-cell lymphomas harboring chromosomal translocations involving the ALK tyrosine kinase. ALCL represents about 10% of all childhood non-Hodgkin lymphoma (NHL). The t(2;5)(p23;q35) chromosomal aberration resulting in overexpression of a chimeric oncogene, nucleophosmin-anaplastic lymphoma kinase (NPM/ALK) is the most common translocation found in these tumors. The NPM/ALK protein plays a key role in ALCL lymphomagenesis and has been shown to cause lymphoid malignancy in vitro and in vivo. Although, the prognosis of localized childhood ALCL is excellent with 5 year survival ranging from 90-95%, children with advanced stage ALCL only have a 5 year survival of about 60% with late relapses are a common complication. Since 70% of children present with advanced disease, 25%-35% of all children with ALCL will relapse or become refractory to initial treatment. Biomarkers of ALCL that can be useful for diagnosis, early detection, prediction of biologic behavior and therapy are needed. Novel targeted therapies are needed for children with refractory/relapsed ALCL and for the subset of children with a poor prognosis at diagnosis. In this application, we propose to utilize a suite of quantitative mass spectrometry-based proteomics strategies supported by sophisticated bioinformatics approaches to identify proteomic biomarkers of NPM/ALK-positive lymphomas. In specific aim 1, we will perform global quantitative proteomic analysis in an unbiased manner to identify the proteomic and phosphoproteomic changes associated with the expression of NPM/ALK in human lymphoid cells. In specific aim 2, we will establish the functional relevance of selected components of the MS-derived NPM/ALK signaling pathways. Our long-term goal is to identify robust, sensitive and specific protein biomarkers for the detection of NPM/ALK-positive ALCLs. Our studies have implications for the identification of disease biomarkers for other forms of cancers characterized by ALK deregulation. PUBLIC HEALTH RELEVANCE: Health-care impact. Children with advanced stage ALCL only have a 5 year event free survival of about 60% with late relapses as a common complication. Since 70% of children present with advanced disease, 25%-35% of all children with ALCL will relapse or become refractory to initial treatment. Biomarkers of ALCL that can be useful for diagnosis, early detection, prediction of biologic behavior and therapy are needed. In addition, novel targeted therapies are needed for children with refractory/relapsed ALCL and for the subset of children with a poor prognosis at diagnosis. In this application, we propose to utilize a suite of quantitative mass spectrometry-based proteomics strategies supported by sophisticated bioinformatics approaches to identify proteomic biomarkers of NPM/ALK-positive lymphomas. Our proposed studies offer an opportunity for the discovery of robust, sensitive biomarkers of ALCL. Collectively, our studies will lead to identification of protein biomarkers of NPM/ALK lymphomas that will be important for the diagnostic assessment, treatment and monitoring of patients with ALCL.
描述(由申请人提供):间变性大细胞淋巴瘤 (ALCL) 是外周 T 细胞淋巴瘤的一种独特亚型,具有涉及 ALK 酪氨酸激酶的染色体易位。 ALCL 约占所有儿童非霍奇金淋巴瘤 (NHL) 的 10%。导致嵌合癌基因核磷蛋白-间变性淋巴瘤激酶 (NPM/ALK) 过度表达的 t(2;5)(p23;q35) 染色体畸变是这些肿瘤中最常见的易位。 NPM/ALK 蛋白在 ALCL 淋巴瘤发生中发挥关键作用,并已在体外和体内显示可导致淋巴恶性肿瘤。虽然局限性儿童 ALCL 的预后良好,5 年生存率为 90-95%,但晚期 ALCL 儿童的 5 年生存率仅为 60% 左右,晚期复发是常见的并发症。由于 70% 的儿童患有晚期疾病,因此所有 ALCL 儿童中有 25%-35% 会复发或对初始治疗变得难治。需要可用于诊断、早期检测、生物学行为预测和治疗的 ALCL 生物标志物。难治性/复发性 ALCL 儿童和诊断时预后不良的儿童需要新的靶向治疗。在此应用中,我们建议利用一套由复杂的生物信息学方法支持的基于定量质谱的蛋白质组学策略来识别 NPM/ALK 阳性淋巴瘤的蛋白质组生物标志物。在具体目标1中,我们将以公正的方式进行全局定量蛋白质组分析,以确定与人淋巴细胞中NPM/ALK表达相关的蛋白质组和磷酸化蛋白质组变化。在具体目标 2 中,我们将建立 MS 衍生的 NPM/ALK 信号通路选定组件的功能相关性。我们的长期目标是确定稳健、灵敏且特异的蛋白质生物标志物,用于检测 NPM/ALK 阳性 ALCL。我们的研究对于识别以 ALK 失调为特征的其他形式癌症的疾病生物标志物具有重要意义。 公共卫生相关性:医疗保健影响。晚期 ALCL 儿童的 5 年无事件生存率仅为 60% 左右,晚期复发是一种常见并发症。由于 70% 的儿童患有晚期疾病,因此所有 ALCL 儿童中有 25%-35% 会复发或对初始治疗变得难治。需要可用于诊断、早期检测、生物学行为预测和治疗的 ALCL 生物标志物。此外,对于难治性/复发性 ALCL 儿童以及诊断时预后不良的儿童子集,需要新的靶向治疗。在此应用中,我们建议利用一套由复杂的生物信息学方法支持的基于定量质谱的蛋白质组学策略来识别 NPM/ALK 阳性淋巴瘤的蛋白质组生物标志物。我们提出的研究为发现 ALCL 稳健、敏感的生物标志物提供了机会。总的来说,我们的研究将确定 NPM/ALK 淋巴瘤的蛋白质生物标志物,这对于 ALCL 患者的诊断评估、治疗和监测非常重要。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Megan S. Lim其他文献

Pilot Study Using Induction Chemo-Immunotherapy Followed By Consolidation with Reduced Toxicity Conditioning and Allogeneic Stem Cell Transplant in Advanced Stage Mature Non-Anaplastic T- or NK-Cell Lymphoma/Leukemia in Children, Adolescent, and Young Adults
  • DOI:
    10.1182/blood-2022-160045
  • 发表时间:
    2022-11-15
  • 期刊:
  • 影响因子:
  • 作者:
    Ana C. Xavier;Lauren Harrison;Rodney R. Miles;Stephan Voss;Megan S. Lim;Mitchell S. Cairo
  • 通讯作者:
    Mitchell S. Cairo
Longitudinal, Real-World Data Reveal Treatment Effectiveness in Idiopathic Multicentric Castleman Disease and Support Current Treatment Guidelines
  • DOI:
    10.1182/blood-2022-170360
  • 发表时间:
    2022-11-15
  • 期刊:
  • 影响因子:
  • 作者:
    Sheila K Pierson;Mateo Sarmiento Bustamante;Joshua D Brandstadter;Daisy Alapat;Adam Bagg;Mary Jo Lechowicz;Gordan Srkalovic;Megan S. Lim;Frits van Rhee;David C Fajgenbaum
  • 通讯作者:
    David C Fajgenbaum
Clinical Laboratory Mutation Analysis Performed on Tumor Biopsies from Patients with Relapsed/Refractory Aggressive B Cell Lymphoma Treated with Palliative-Intent Therapy
  • DOI:
    10.1182/blood-2022-165086
  • 发表时间:
    2022-11-15
  • 期刊:
  • 影响因子:
  • 作者:
    Danielle F Soberman;Jennifer J.D. Morrissette;Stephen J. Schuster;Sunita Dwivedy Nasta;James N. Gerson;Stefan K. Barta;Jakub Svoboda;Elise A. Chong;Megan S. Lim;Daniel J. Landsburg
  • 通讯作者:
    Daniel J. Landsburg
The Diagnostic Utility of TRBC1 Immunohistochemistry in Mature T-Cell Lymphomas
TRBC1免疫组织化学在成熟T细胞淋巴瘤中的诊断效用
  • DOI:
    10.1016/j.modpat.2025.100725
  • 发表时间:
    2025-06-01
  • 期刊:
  • 影响因子:
    5.500
  • 作者:
    Ting Zhou;Rohan Sardana;Ozgur Can Eren;Melissa Pulitzer;Achim Jungbluth;Ahmet Dogan;Megan S. Lim
  • 通讯作者:
    Megan S. Lim
The <em>NPM1</em>-<em>TYK2</em> Chimeric Fusion Promotes Activation of STAT Family Signaling, Skewing Towards Tfh Functional Subset Differentiation and Mature T-Cell Lymphomagenesis
  • DOI:
    10.1182/blood-2022-169494
  • 发表时间:
    2022-11-15
  • 期刊:
  • 影响因子:
  • 作者:
    Huang-Chang Liang;Richa Kapoor;Ozlem Onder;Kevin Dennis;Megan S. Lim;Kojo S.J. Elenitoba-Johnson
  • 通讯作者:
    Kojo S.J. Elenitoba-Johnson

Megan S. Lim的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Megan S. Lim', 18)}}的其他基金

Genomic biomarkers for cutaneous T-cell Lymphoma
皮肤 T 细胞淋巴瘤的基因组生物标志物
  • 批准号:
    10550139
  • 财政年份:
    2022
  • 资助金额:
    $ 32.06万
  • 项目类别:
Genomic biomarkers for cutaneous T-cell Lymphoma
皮肤 T 细胞淋巴瘤的基因组生物标志物
  • 批准号:
    10703843
  • 财政年份:
    2022
  • 资助金额:
    $ 32.06万
  • 项目类别:
Circulating biomarkers of ALK+ anaplastic large cell lymphoma
ALK 间变性大细胞淋巴瘤的循环生物标志物
  • 批准号:
    10703855
  • 财政年份:
    2022
  • 资助金额:
    $ 32.06万
  • 项目类别:
Circulating biomarkers of ALK+ anaplastic large cell lymphoma
ALK 间变性大细胞淋巴瘤的循环生物标志物
  • 批准号:
    10680558
  • 财政年份:
    2022
  • 资助金额:
    $ 32.06万
  • 项目类别:
Circulating biomarkers of ALK+ anaplastic large cell lymphoma
ALK 间变性大细胞淋巴瘤的循环生物标志物
  • 批准号:
    10298658
  • 财政年份:
    2021
  • 资助金额:
    $ 32.06万
  • 项目类别:
Circulating biomarkers of ALK+ anaplastic large cell lymphoma
ALK 间变性大细胞淋巴瘤的循环生物标志物
  • 批准号:
    10470371
  • 财政年份:
    2021
  • 资助金额:
    $ 32.06万
  • 项目类别:
Genomic biomarkers for cutaneous T-cell Lymphoma
皮肤 T 细胞淋巴瘤的基因组生物标志物
  • 批准号:
    10321292
  • 财政年份:
    2020
  • 资助金额:
    $ 32.06万
  • 项目类别:
Genomic biomarkers for cutaneous T-cell Lymphoma
皮肤 T 细胞淋巴瘤的基因组生物标志物
  • 批准号:
    9884667
  • 财政年份:
    2020
  • 资助金额:
    $ 32.06万
  • 项目类别:
Proteomic biomarkers of ALK+ lymphoma
ALK 淋巴瘤的蛋白质组生物标志物
  • 批准号:
    8385569
  • 财政年份:
    2009
  • 资助金额:
    $ 32.06万
  • 项目类别:
Proteomic biomarkers of ALK+ lymphoma
ALK 淋巴瘤的蛋白质组生物标志物
  • 批准号:
    8196784
  • 财政年份:
    2009
  • 资助金额:
    $ 32.06万
  • 项目类别:

相似海外基金

Digital cognitive-behavior therapy for anxiety and depressive disorders: Building an impactful research project from international partnerships and knowledge exchange in primary care
针对焦虑和抑郁症的数字认知行为疗法:通过初级保健领域的国际合作和知识交流建立一个有影响力的研究项目
  • 批准号:
    480808
  • 财政年份:
    2023
  • 资助金额:
    $ 32.06万
  • 项目类别:
    Miscellaneous Programs
Function of cost bias and effect of cognitive behavior therapy on social anxiety in children and adolescents
成本偏差的作用及认知行为治疗对儿童青少年社交焦虑的影响
  • 批准号:
    23K02970
  • 财政年份:
    2023
  • 资助金额:
    $ 32.06万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Combined Dialectical Behavior Therapy and Digital Cognitive Behavioral Therapy for Insomnia for Adolescents at High Risk for Suicide: A Pilot RCT
辩证行为疗法和数字认知行为疗法相结合治疗自杀高危青少年的失眠:一项试点随机对照试验
  • 批准号:
    10643478
  • 财政年份:
    2023
  • 资助金额:
    $ 32.06万
  • 项目类别:
A Randomized Clinical Trial Comparing Transdiagnostic Behavior Therapy to Disorder-Specific Psychotherapy in the Recovery of Veterans with Social Anxiety Disorder and Comorbid PTSD Symptomatology
一项随机临床试验,比较跨诊断行为疗法与特定障碍心理疗法在患有社交焦虑症和共病 PTSD 症状的退伍军人康复中的作用
  • 批准号:
    10746930
  • 财政年份:
    2023
  • 资助金额:
    $ 32.06万
  • 项目类别:
Reducing suicide risk among aging caregivers of persons with AD/ADRD: Adapting, implementing, and evaluating Dialectical Behavior Therapy skills training interventions.
降低 AD/ADRD 患者老年护理人员的自杀风险:调整、实施和评估辩证行为治疗技能培训干预措施。
  • 批准号:
    10730708
  • 财政年份:
    2023
  • 资助金额:
    $ 32.06万
  • 项目类别:
A Randomized control trial of behavior therapy of tics in Japan. Exploring the behavior model of tics.
日本抽动行为治疗的随机对照试验。
  • 批准号:
    22K13840
  • 财政年份:
    2022
  • 资助金额:
    $ 32.06万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
The Role of Behavior Therapy Combined with Buprenorphine for the Treatment of Opioid Use Disorder
行为疗法联合丁丙诺啡治疗阿片类药物使用障碍的作用
  • 批准号:
    10440820
  • 财政年份:
    2022
  • 资助金额:
    $ 32.06万
  • 项目类别:
Efficacy of digital cognitive behavior therapy for insomnia for the prevention of perinatal depression
数字认知行为疗法治疗失眠预防围产期抑郁症的疗效
  • 批准号:
    10429841
  • 财政年份:
    2022
  • 资助金额:
    $ 32.06万
  • 项目类别:
Efficacy of digital cognitive behavior therapy for insomnia for the prevention of perinatal depression
数字认知行为疗法治疗失眠预防围产期抑郁症的疗效
  • 批准号:
    10656415
  • 财政年份:
    2022
  • 资助金额:
    $ 32.06万
  • 项目类别:
Efficacy of digital cognitive behavior therapy for insomnia for the prevention of perinatal depression - supplement
数字认知行为疗法治疗失眠预防围产期抑郁症的疗效 - 补充
  • 批准号:
    10794868
  • 财政年份:
    2022
  • 资助金额:
    $ 32.06万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了