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  1. Article ; Online: Protein profiling by reverse phase protein array (RPPA) in classical hairy cell leukemia (HCL) and HCL-variant.

    Hoff, Fieke W / Griffen, Ti'ara L / Qiu, Yihua / Kornblau, Steven M

    EJHaem

    2022  Volume 3, Issue 4, Page(s) 1321–1325

    Abstract: Classical hairy cell leukemia (HCL-c) and HCL variant (HCL-v) are recognized as separate entities with HCL-v having significantly shorter overall survival. Proteomic studies, shown to be prognostic in various forms of leukemia, have not been performed in ...

    Abstract Classical hairy cell leukemia (HCL-c) and HCL variant (HCL-v) are recognized as separate entities with HCL-v having significantly shorter overall survival. Proteomic studies, shown to be prognostic in various forms of leukemia, have not been performed in HCL. We performed reverse phase protein array-based protein profiling with 384 antibodies in HCL-c (
    Language English
    Publishing date 2022-09-02
    Publishing country United States
    Document type Journal Article
    ISSN 2688-6146
    ISSN (online) 2688-6146
    DOI 10.1002/jha2.558
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Reverse phase protein arrays in acute leukemia: investigative and methodological challenges.

    Hoff, Fieke W / Horton, Terzah M / Kornblau, Steven M

    Expert review of proteomics

    2021  Volume 18, Issue 12, Page(s) 1087–1097

    Abstract: Introduction: Acute leukemia results from a series of mutational events that alter cell growth and proliferation. Mutations result in protein changes that orchestrate growth alterations characteristic of leukemia. Proteomics is a methodology appropriate ...

    Abstract Introduction: Acute leukemia results from a series of mutational events that alter cell growth and proliferation. Mutations result in protein changes that orchestrate growth alterations characteristic of leukemia. Proteomics is a methodology appropriate for study of protein changes found in leukemia. The high-throughput reverse phase protein array (RPPA) technology is particularly well-suited for the assessment of protein changes in samples derived from clinical trials.
    Areas covered: This review discusses the technical, methodological, and analytical issues related to the successful development of acute leukemia RPPAs.
    Expert commentary: To obtain representative protein sample lysates, samples should be prepared from freshly collected blood or bone marrow material. Variables such as sample shipment, transit time, and holding temperature only have minimal effects on protein expression. CellSave preservation tubes are preferred for cells collected after exposure to chemotherapy, and incorporation of standardized guidelines for antibody validation is recommended. A more systematic biological approach to analyze protein expression is desired, searching for recurrent patterns of protein expression that allow classification of patients into risk groups, or groups of patients that may be treated similarly. Comparing RPPA protein analysis between cell lines and primary samples shows that cell lines are not representative of patient proteomic patterns.
    MeSH term(s) Humans ; Leukemia, Myeloid, Acute/drug therapy ; Protein Array Analysis ; Protein Processing, Post-Translational ; Proteins ; Proteomics
    Chemical Substances Proteins
    Language English
    Publishing date 2021-12-29
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2299100-1
    ISSN 1744-8387 ; 1478-9450
    ISSN (online) 1744-8387
    ISSN 1478-9450
    DOI 10.1080/14789450.2021.2020655
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  3. Article ; Online: Prognostication of DNA Damage Response Protein Expression Patterns in Chronic Lymphocytic Leukemia.

    Griffen, Ti'ara L / Hoff, Fieke W / Qiu, Yihua / Burger, Jan / Wierda, William / Kornblau, Steven M

    International journal of molecular sciences

    2023  Volume 24, Issue 6

    Abstract: Proteomic DNA Damage Repair (DDR) expression patterns in Chronic Lymphocytic Leukemia were characterized by quantifying and clustering 24 total and phosphorylated DDR proteins. Overall, three protein expression patterns (C1-C3) were identified and were ... ...

    Abstract Proteomic DNA Damage Repair (DDR) expression patterns in Chronic Lymphocytic Leukemia were characterized by quantifying and clustering 24 total and phosphorylated DDR proteins. Overall, three protein expression patterns (C1-C3) were identified and were associated as an independent predictor of distinct patient overall survival outcomes. Patients within clusters C1 and C2 had poorer survival outcomes and responses to fludarabine, cyclophosphamide, and rituxan chemotherapy compared to patients within cluster C3. However, DDR protein expression patterns were not prognostic in more modern therapies with BCL2 inhibitors or a BTK/PI3K inhibitor. Individually, nine of the DDR proteins were prognostic for predicting overall survival and/or time to first treatment. When looking for other proteins that may be associated with or influenced by DDR expression patterns, our differential expression analysis found that cell cycle and adhesion proteins were lower in clusters compared to normal CD19 controls. In addition, cluster C3 had a lower expression of MAPK proteins compared to the poor prognostic patient clusters thus implying a potential regulatory connection between adhesion, cell cycle, MAPK, and DDR signaling in CLL. Thus, assessing the proteomic expression of DNA damage proteins in CLL provided novel insights for deciphering influences on patient outcomes and expanded our understanding of the potential complexities and effects of DDR cell signaling.
    MeSH term(s) Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/metabolism ; Phosphatidylinositol 3-Kinases/genetics ; Proteomics ; DNA Damage ; Discoidin Domain Receptors/genetics
    Chemical Substances Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Discoidin Domain Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2023-03-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24065481
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  4. Article ; Online: DNA Damage Response-Related Proteins Are Prognostic for Outcome in Both Adult and Pediatric Acute Myelogenous Leukemia Patients: Samples from Adults and from Children Enrolled in a Children's Oncology Group Study.

    Hubner, Stefan E / de Camargo Magalhães, Eduardo S / Hoff, Fieke W / Brown, Brandon D / Qiu, Yihua / Horton, Terzah M / Kornblau, Steven M

    International journal of molecular sciences

    2023  Volume 24, Issue 6

    Abstract: The survival of malignant leukemic cells is dependent on DNA damage repair (DDR) signaling. Reverse Phase Protein Array (RPPA) data sets were assembled using diagnostic samples from 810 adult and 500 pediatric acute myelogenous leukemia (AML) patients ... ...

    Abstract The survival of malignant leukemic cells is dependent on DNA damage repair (DDR) signaling. Reverse Phase Protein Array (RPPA) data sets were assembled using diagnostic samples from 810 adult and 500 pediatric acute myelogenous leukemia (AML) patients and were probed with 412 and 296 strictly validated antibodies, respectively, including those detecting the expression of proteins directly involved in DDR. Unbiased hierarchical clustering identified strong recurrent DDR protein expression patterns in both adult and pediatric AML. Globally, DDR expression was associated with gene mutational statuses and was prognostic for outcomes including overall survival (OS), relapse rate, and remission duration (RD). In adult patients, seven DDR proteins were individually prognostic for either RD or OS. When DDR proteins were analyzed together with DDR-related proteins operating in diverse cellular signaling pathways, these expanded groupings were also highly prognostic for OS. Analysis of patients treated with either conventional chemotherapy or venetoclax combined with a hypomethylating agent revealed protein clusters that differentially predicted favorable from unfavorable prognoses within each therapy cohort. Collectively, this investigation provides insight into variable DDR pathway activation in AML and may help direct future individualized DDR-targeted therapies in AML patients.
    MeSH term(s) Humans ; Adult ; Child ; Prognosis ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/pathology ; DNA Repair/genetics ; DNA Damage ; Discoidin Domain Receptors/genetics
    Chemical Substances Discoidin Domain Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2023-03-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24065898
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  5. Article: Antibody Screening.

    Hoff, Fieke W / Lu, Yiling / Kornblau, Steven M

    Advances in experimental medicine and biology

    2019  Volume 1188, Page(s) 149–163

    Abstract: Antibodies are among the most frequently used tools in research and have had a profound impact on the discovery of diagnostic and therapeutic targets and the understanding of the molecular background of diseases. In particular in reverse phase protein ... ...

    Abstract Antibodies are among the most frequently used tools in research and have had a profound impact on the discovery of diagnostic and therapeutic targets and the understanding of the molecular background of diseases. In particular in reverse phase protein arrays (RPPA), where there is no separation of the proteins according to molecular weight, it is crucial that antibodies are proven to be highly specific, selective, and reproducible. However, numerous studies have shown that many antibodies frequently do not recognize the protein that they are supposed to detect, that multiple antibodies do often function in one application but not in another, and that antibodies are not stable over time or between different batches. So far, no universally accepted guidelines or standardized methods for determining the validity of antibodies have been established. This chapter discusses the urgent need for antibody validation, current strategies that are used for (RPPA) antibody validation, as well as proposes a new strategy about how to report, score, and integrate antibody validation from multiple users.
    MeSH term(s) Antibodies/analysis ; Antibodies/metabolism ; Protein Array Analysis ; Proteins/chemistry ; Proteins/metabolism
    Chemical Substances Antibodies ; Proteins
    Language English
    Publishing date 2019-12-16
    Publishing country United States
    Document type Journal Article
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-981-32-9755-5_8
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  6. Article: Decomposing the Apoptosis Pathway Into Biologically Interpretable Principal Components.

    Wang, Min / Kornblau, Steven M / Coombes, Kevin R

    Cancer informatics

    2018  Volume 17, Page(s) 1176935118771082

    Abstract: Principal component analysis (PCA) is one of the most common techniques in the analysis of biological data sets, but applying PCA raises 2 challenges. First, one must determine the number of significant principal components (PCs). Second, because each PC ...

    Abstract Principal component analysis (PCA) is one of the most common techniques in the analysis of biological data sets, but applying PCA raises 2 challenges. First, one must determine the number of significant principal components (PCs). Second, because each PC is a linear combination of genes, it rarely has a biological interpretation. Existing methods to determine the number of PCs are either subjective or computationally extensive. We review several methods and describe a new R package, PCDimension, that implements additional methods, the most important being an algorithm that extends and automates a graphical Bayesian method. Using simulations, we compared the methods. Our newly automated procedure is competitive with the best methods when considering both accuracy and speed and is the most accurate when the number of objects is small compared with the number of attributes. We applied the method to a proteomics data set from patients with acute myeloid leukemia. Proteins in the apoptosis pathway could be explained using 6 PCs. By clustering the proteins in PC space, we were able to replace the PCs by 6 "biological components," 3 of which could be immediately interpreted from the current literature. We expect this approach combining PCA with clustering to be widely applicable.
    Language English
    Publishing date 2018-05-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2202739-7
    ISSN 1176-9351
    ISSN 1176-9351
    DOI 10.1177/1176935118771082
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  7. Article ; Online: Vecabrutinib inhibits B-cell receptor signal transduction in chronic lymphocytic leukemia cell types with wild-type or mutant Bruton tyrosine kinase.

    Aslan, Burcu / Hubner, Stefan Edward / Fox, Judith A / Taverna, Pietro / Wierda, William G / Kornblau, Steven M / Gandhi, Varsha

    Haematologica

    2022  Volume 107, Issue 1, Page(s) 292–297

    MeSH term(s) Agammaglobulinaemia Tyrosine Kinase ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Receptors, Antigen, B-Cell/genetics ; Receptors, Antigen, B-Cell/metabolism ; Signal Transduction
    Chemical Substances Protein Kinase Inhibitors ; Receptors, Antigen, B-Cell ; Agammaglobulinaemia Tyrosine Kinase (EC 2.7.10.2)
    Language English
    Publishing date 2022-01-01
    Publishing country Italy
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2021.279158
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  8. Article: Chromatin Profiles Are Prognostic of Clinical Response to Bortezomib-Containing Chemotherapy in Pediatric Acute Myeloid Leukemia: Results from the COG AAML1031 Trial.

    van Dijk, Anneke D / Hoff, Fieke W / Qiu, Yihua / Hubner, Stefan E / Go, Robin L / Ruvolo, Vivian R / Leonti, Amanda R / Gerbing, Robert B / Gamis, Alan S / Aplenc, Richard / Kolb, Edward A / Alonzo, Todd A / Meshinchi, Soheil / de Bont, Eveline S J M / Horton, Terzah M / Kornblau, Steven M

    Cancers

    2024  Volume 16, Issue 8

    Abstract: The addition of the proteasome inhibitor bortezomib to standard chemotherapy did not improve survival in pediatric acute myeloid leukemia (AML) when all patients were analyzed as a group in the Children's Oncology Group phase 3 trial AAML1031 ( ... ...

    Abstract The addition of the proteasome inhibitor bortezomib to standard chemotherapy did not improve survival in pediatric acute myeloid leukemia (AML) when all patients were analyzed as a group in the Children's Oncology Group phase 3 trial AAML1031 (NCT01371981). Proteasome inhibition influences the chromatin landscape and proteostasis, and we hypothesized that baseline proteomic analysis of histone- and chromatin-modifying enzymes (HMEs) would identify AML subgroups that benefitted from bortezomib addition. A proteomic profile of 483 patients treated with AAML1031 chemotherapy was generated using a reverse-phase protein array. A relatively high expression of 16 HME was associated with lower EFS and higher 3-year relapse risk after AML standard treatment compared to low expressions (52% vs. 29%,
    Language English
    Publishing date 2024-04-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers16081448
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  9. Article ; Online: Targeted therapy in acute myeloid leukemia: current status and new insights from a proteomic perspective.

    van Dijk, Anneke D / de Bont, Eveline S J M / Kornblau, Steven M

    Expert review of proteomics

    2020  Volume 17, Issue 1, Page(s) 1–10

    Abstract: ... ...

    Abstract Introduction
    MeSH term(s) Animals ; Antineoplastic Agents/therapeutic use ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/metabolism ; Mass Spectrometry/methods ; Molecular Targeted Therapy/methods ; Proteome/genetics ; Proteome/metabolism ; Proteomics/methods ; Translational Medical Research/methods
    Chemical Substances Antineoplastic Agents ; Proteome
    Language English
    Publishing date 2020-01-23
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2299100-1
    ISSN 1744-8387 ; 1478-9450
    ISSN (online) 1744-8387
    ISSN 1478-9450
    DOI 10.1080/14789450.2020.1717951
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  10. Article ; Online: p53 pathway dysfunction in AML: beyond

    Post, Sean M / Kornblau, Steven M / Quintás-Cardama, Alfonso

    Oncotarget

    2017  Volume 8, Issue 65, Page(s) 108288–108289

    Language English
    Publishing date 2017-12-12
    Publishing country United States
    Document type Editorial
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.22713
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