PubTransformer

A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Morphoproteomics Identifies SIRT1 and EZH2 Pathways as Commonalities in B-cell Acute Lymphoblastic Leukemia: Pathogenetic Implications and Opportunities for Therapeutic Intervention.

Abstract B-cell acute lymphoblastic leukemia (ALL) represents a malignant process in which bone marrow-derived lymphoblasts retain their undifferentiated state. Genetic testing has revealed either no identifiable cytogenetic and genomic abnormalities in such patients or a wide range of aberrations that may or may not contribute to the block in differentiation and the associated proliferation of the malignant lymphoblasts in cases of B-cell ALL. In this study, we applied morphoproteomics to a representative spectrum of cases of newly diagnosed B-cell ALL in order to identify pathways that are known to be associated with the maintenance of the undifferentiated state while promoting proliferation. Our results showed nuclear expression in a majority of the lymphoblasts from bone marrow clot preparations of each of the study cases for both silent mating type information regulation 2 homolog 1 (SIRT1), an NAD+ histone deacetylase and enhancer of Zeste homolog 2 (EZH2), a histone methyltransferase. These represent pathogenetic pathways capable of blocking differentiation and promoting proliferation of the B-cell ALL lymphoblasts. Data mining of the National Library of Medicine's MEDLINE Database and Ingenuity Pathway analysis revealed agents of relatively low toxicity-melatonin, metformin, curcumin and sulforaphane-that are capable of inhibiting directly or pharmacogenomically one or both of the SIRT1 and EZH2 pathways and should, in a combinatorial fashion, remove the block in differentiation and decrease the proliferation of the B-cell ALL lymphoblasts.
PMID
Related Publications

Genomic pathway analysis reveals that EZH2 and HDAC4 represent mutually exclusive epigenetic pathways across human cancers.

Enhancer of zeste homolog 2 is overexpressed and contributes to epigenetic inactivation of p21 and phosphatase and tensin homolog in B-cell acute lymphoblastic leukemia.

NUT Midline Carcinoma: Morphoproteomic Characterization with Genomic and Therapeutic Correlates.

Morphoproteomics identifies constitutive activation of the mTORC2/Akt and NF-κB pathways and expressions of IGF-1R, Sirt1, COX-2, and FASN in peripheral T-cell lymphomas: pathogenetic implications and therapeutic options.

Morphoproteomics Identifies the EZH2 and SIRT1 Pathways as Potential Blocks to Differentiation in Yolk Sac Tumor of the Ovary and Provides Therapeutic Options: a Case Study.

Authors

Mayor MeshTerms
Keywords

B-cell ALL

EZH2

SIRT1

morphoproteomics

Journal Title annals of clinical and laboratory science
Publication Year Start




PMID- 28249909
OWN - NLM
STAT- In-Process
DA  - 20170302
LR  - 20170302
IS  - 1550-8080 (Electronic)
IS  - 0091-7370 (Linking)
VI  - 47
IP  - 1
DP  - 2017 Jan
TI  - Morphoproteomics Identifies SIRT1 and EZH2 Pathways as Commonalities in B-cell
      Acute Lymphoblastic Leukemia: Pathogenetic Implications and Opportunities for
      Therapeutic Intervention.
PG  - 3-9
AB  - B-cell acute lymphoblastic leukemia (ALL) represents a malignant process in which
      bone marrow-derived lymphoblasts retain their undifferentiated state. Genetic
      testing has revealed either no identifiable cytogenetic and genomic abnormalities
      in such patients or a wide range of aberrations that may or may not contribute to
      the block in differentiation and the associated proliferation of the malignant
      lymphoblasts in cases of B-cell ALL. In this study, we applied morphoproteomics
      to a representative spectrum of cases of newly diagnosed B-cell ALL in order to
      identify pathways that are known to be associated with the maintenance of the
      undifferentiated state while promoting proliferation. Our results showed nuclear 
      expression in a majority of the lymphoblasts from bone marrow clot preparations
      of each of the study cases for both silent mating type information regulation 2
      homolog 1 (SIRT1), an NAD+ histone deacetylase and enhancer of Zeste homolog 2
      (EZH2), a histone methyltransferase. These represent pathogenetic pathways
      capable of blocking differentiation and promoting proliferation of the B-cell ALL
      lymphoblasts. Data mining of the National Library of Medicine's MEDLINE Database 
      and Ingenuity Pathway analysis revealed agents of relatively low
      toxicity-melatonin, metformin, curcumin and sulforaphane-that are capable of
      inhibiting directly or pharmacogenomically one or both of the SIRT1 and EZH2
      pathways and should, in a combinatorial fashion, remove the block in
      differentiation and decrease the proliferation of the B-cell ALL lymphoblasts.
CI  - (c) 2017 by the Association of Clinical Scientists, Inc.
FAU - Brown, Robert E
AU  - Brown RE
AD  - Department of Pathology and Laboratory Medicine, UTHealth, McGovern Medical
      School, Houston, Texas, USA Robert.Brown@uth.tmc.edu.
FAU - Konopka, Kristine E
AU  - Konopka KE
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
FAU - Weerasinghe, Priya
AU  - Weerasinghe P
AD  - Department of Pathology and Laboratory Medicine, UTHealth, McGovern Medical
      School, Houston, Texas, USA.
FAU - Jaitly, Vanya
AU  - Jaitly V
AD  - Department of Pathology and Laboratory Medicine, UTHealth, McGovern Medical
      School, Houston, Texas, USA.
FAU - Dasgupta, Amitava
AU  - Dasgupta A
AD  - Department of Pathology and Laboratory Medicine, UTHealth, McGovern Medical
      School, Houston, Texas, USA.
FAU - McGuire, Mary F
AU  - McGuire MF
AD  - Biomedical Analytics, Houston, Texas, USA.
FAU - Nguyen, Nghia D
AU  - Nguyen ND
AD  - Department of Pathology and Laboratory Medicine, UTHealth, McGovern Medical
      School, Houston, Texas, USA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Ann Clin Lab Sci
JT  - Annals of clinical and laboratory science
JID - 0410247
OTO - NOTNLM
OT  - B-cell ALL
OT  - EZH2
OT  - SIRT1
OT  - morphoproteomics
EDAT- 2017/03/03 06:00
MHDA- 2017/03/03 06:00
CRDT- 2017/03/03 06:00
AID - 47/1/3 [pii]
PST - ppublish
SO  - Ann Clin Lab Sci. 2017 Jan;47(1):3-9.

<?xml version="1.0" encoding="UTF-8"?>
<b:Sources SelectedStyle="" xmlns:b="http://schemas.openxmlformats.org/officeDocument/2006/bibliography"  xmlns="http://schemas.openxmlformats.org/officeDocument/2006/bibliography" >
</b:Sources>