<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03267485</url>
  </required_header>
  <id_info>
    <org_study_id>TET1 gene in acute leukemia</org_study_id>
    <nct_id>NCT03267485</nct_id>
  </id_info>
  <brief_title>Expression of TET1 Gene in Acute Leukaemia</brief_title>
  <official_title>Expression of TET1 Gene in Acute Leukaemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the present study is to detect the expression of TET 1 gene in patients with acute&#xD;
      leukemia and its correlation with clinical and pathological criteria of the patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      &quot;Acute leukemia&quot; is defined by the World Health organization standards, in which greater than&#xD;
      20% of the cells in the bone marrow are blasts (Kabuto et al., 2006). Cure is a realistic&#xD;
      goal and is achieved in more than 80% of affected children, although only 20-40% of adults&#xD;
      are cured(Rose-Inman and Kuehl, 2014).&#xD;
&#xD;
      There are two major forms of acute leukaemias-acute lymphoblastic leukaemia (ALL) and acute&#xD;
      myeloid leukaemia (AML) Acute lymphoblastic leukemia (ALL) is an acute form of&#xD;
      leukemiacharacterized by the overproduction and accumulation of cancerous, immature white&#xD;
      blood cells, known as lymphoblasts(Rose-Inman and Kuehl, 2014).&#xD;
&#xD;
      Internationally, ALL is more common in Caucasians than in Africans; it is more common in&#xD;
      Hispanics and in Latin America(Greer, 2014; Urayama and Manabe, 2014).About 6,000 cases are&#xD;
      reported in the United States every year(Inaba et al., 2013).&#xD;
&#xD;
      Acute Myeloid leukemia (AML)Acute Myeloid Leukemia is a cancer of leukemic stem cells (LSCs)&#xD;
      with a rapid progression. It is characterized by overproduction of immature myeloid cells in&#xD;
      bone marrow which crowds out normal hematopoietic stem cells (HSC) (Indian J Hematol Blood&#xD;
      Transfus. 2017).&#xD;
&#xD;
      DNA methylation is a covalent modification that is critical for the regulation of gene&#xD;
      expression in a wide variety of biological contexts (Jaenisch and Bird, 2003; Bergman and&#xD;
      Cedar, 2013). Methylation of DNA on cytosines is an important mechanism for silencing gene&#xD;
      expression, and cytosine demethylation is required for gene activation (Ito et al., 2011; He&#xD;
      et al., 2011). DNA methylation plays important roles in a variety of cellular processes,&#xD;
      including genomic imprinting , X-chromosome inactivation and regulation of gene expression&#xD;
      (Bird 2002).&#xD;
&#xD;
      The ten-eleven translocation (Tet) family of methylcytosine dioxygenases, which includes&#xD;
      Tet1, Tet2, and Tet3 enzymes, has been recently implicated in DNA demethylation it converts&#xD;
      5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) as well as to 5-formylcytosine and&#xD;
      5-carboxylcytosine (Tahiliani et al., 2009; Ito et al., 2010; Guo et al., 2011a). 5hmC has&#xD;
      been proposed to act as an intermediate in demethylation and the base-excision repair&#xD;
      machinery (Guo et al., 2011a).&#xD;
&#xD;
      Tet proteins contain several conserved domains (Tahiliani et al. 2009), including a CXXC&#xD;
      domain that has high affinity for clustered unmethylated CpG dinucleotides and a catalytic&#xD;
      domain that is typical of Fe(II)- and 2-oxoglutarate (2OG)-dependent dioxygenases (Loenarz&#xD;
      and Schofield 2011) ), mutation of iron-binding sites of Tet proteins abolishes their&#xD;
      enzymatic activities (Tahiliani et al. 2009; Ito et al. 2010). In addition,&#xD;
      2-hydroxyglutarate (2-HG), a competitive inhibitor of 2OG-dependent dioxygenases, suppresses&#xD;
      the catalytic activity of Tet proteins (W Xu et al. 2011).Both fully methylated and&#xD;
      hemimethylated DNA in a CG or non-CG context can serve as substrates for TET1 (Tahiliani et&#xD;
      al. 2009; Ficz et al. 2011; Pastor et al. 2011). In tumor cells, the normal pattern of DNA&#xD;
      methylation is often altered, resulting in global hypomethylation of the genome in&#xD;
      conjunction with hypermethylation at CpG islands within the promoters of critical genes such&#xD;
      as tumor suppressors (Esteller, 2008).&#xD;
&#xD;
      The TET1 gene, was initially identified in acute myeloid leukemia (AML) as a fusion partner&#xD;
      of the histone H3 Lys 4 (H3K4) methyltransferase MLL (mixed-lineage leukemia) (Ono et al.&#xD;
      2002; Lorsbach et al. 2003). TET1 is significantly upregulated and plays an oncogenic role in&#xD;
      MLL-rearranged leukemia, rendering TET1 as a potential target for treating this form of&#xD;
      hematopoietic malignancy ( Huang et al., 2013). Tet1 is abundantly expressed in hematopoietic&#xD;
      stem/progenitor cells (HSC/HPCs) and differentiated lineages such as B cells and myeloid&#xD;
      cells (Huang et al., 2013; Li et al., 2011 ; Moran-Crusio et al., 2011)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">November 1, 2017</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">November 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>expression of TET1 gene in acute leukemia</measure>
    <time_frame>baseline</time_frame>
    <description>role of TET1 gene expression in leukemogenesis</description>
  </primary_outcome>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Acute Leukemia</condition>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>real time PCR</intervention_name>
    <description>Real Time PCR is based on the detection of the fluorescence produced by a reporter molecule which increases, as the reaction proceeds. These fluorescent reporter molecules include dyes that bind to the double-stranded DNA or sequence specific probes . Moreover, there is no need for the post PCR processing which saves the resources and the time. .</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        acute leukemia patients at diagnosis or relapse .&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - sample from acute leukemia patients at diagnosis or relapse . healthy subjects as control&#xD;
        .&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients having any other haematological malignancies.&#xD;
&#xD;
          -  Patient with acute leukemia in remission&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_contact>
    <last_name>Monica Botros</last_name>
    <phone>+201069195672</phone>
    <email>monecabotros@yahoo.com</email>
  </overall_contact>
  <reference>
    <citation>Jain A, Varma S, Garg R, Malhotra P. Unilateral Gynaecomastia in a Young Man with Chronic Myeloid Leukemia. Indian J Hematol Blood Transfus. 2017 Sep;33(3):448-450. doi: 10.1007/s12288-016-0762-z. Epub 2016 Dec 19.</citation>
    <PMID>28824259</PMID>
  </reference>
  <reference>
    <citation>Lee BS, Jan YD, Huang GS, Huang CH, Chou HY, Wang JS, Tseng WY. Effect of dentin bonding agent diffusing through dentin slices on the reactive oxygen species production and apoptosis of pulpal cells. J Formos Med Assoc. 2015 Apr;114(4):339-46. doi: 10.1016/j.jfma.2012.12.009. Epub 2013 Feb 13.</citation>
    <PMID>25839767</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>August 29, 2017</last_update_submitted>
  <last_update_submitted_qc>August 29, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Monica Botros Mosaad</investigator_full_name>
    <investigator_title>Resident doctor of clinical pathology department South Egypt Cancer Institute</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Acute Disease</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03267485
org study id: TET1 gene in acute leukemia
nct id: NCT03267485
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The aim of the present study is to detect the expression of TET 1 gene in patients with acute
      leukemia and its correlation with clinical and pathological criteria of the patients.
"Acute leukemia" is defined by the World Health organization standards, in which greater than
      20% of the cells in the bone marrow are blasts (Kabuto et al., 2006). Cure is a realistic
      goal and is achieved in more than 80% of affected children, although only 20-40% of adults
      are cured(Rose-Inman and Kuehl, 2014).

      There are two major forms of acute leukaemias-acute lymphoblastic leukaemia (ALL) and acute
      myeloid leukaemia (AML) Acute lymphoblastic leukemia (ALL) is an acute form of
      leukemiacharacterized by the overproduction and accumulation of cancerous, immature white
      blood cells, known as lymphoblasts(Rose-Inman and Kuehl, 2014).

      Internationally, ALL is more common in Caucasians than in Africans; it is more common in
      Hispanics and in Latin America(Greer, 2014; Urayama and Manabe, 2014).About 6,000 cases are
      reported in the United States every year(Inaba et al., 2013).

      Acute Myeloid leukemia (AML)Acute Myeloid Leukemia is a cancer of leukemic stem cells (LSCs)
      with a rapid progression. It is characterized by overproduction of immature myeloid cells in
      bone marrow which crowds out normal hematopoietic stem cells (HSC) (Indian J Hematol Blood
      Transfus. 2017).

      DNA methylation is a covalent modification that is critical for the regulation of gene
      expression in a wide variety of biological contexts (Jaenisch and Bird, 2003; Bergman and
      Cedar, 2013). Methylation of DNA on cytosines is an important mechanism for silencing gene
      expression, and cytosine demethylation is required for gene activation (Ito et al., 2011; He
      et al., 2011). DNA methylation plays important roles in a variety of cellular processes,
      including genomic imprinting , X-chromosome inactivation and regulation of gene expression
      (Bird 2002).

      The ten-eleven translocation (Tet) family of methylcytosine dioxygenases, which includes
      Tet1, Tet2, and Tet3 enzymes, has been recently implicated in DNA demethylation it converts
      5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) as well as to 5-formylcytosine and
      5-carboxylcytosine (Tahiliani et al., 2009; Ito et al., 2010; Guo et al., 2011a). 5hmC has
      been proposed to act as an intermediate in demethylation and the base-excision repair
      machinery (Guo et al., 2011a).

      Tet proteins contain several conserved domains (Tahiliani et al. 2009), including a CXXC
      domain that has high affinity for clustered unmethylated CpG dinucleotides and a catalytic
      domain that is typical of Fe(II)- and 2-oxoglutarate (2OG)-dependent dioxygenases (Loenarz
      and Schofield 2011) ), mutation of iron-binding sites of Tet proteins abolishes their
      enzymatic activities (Tahiliani et al. 2009; Ito et al. 2010). In addition,
      2-hydroxyglutarate (2-HG), a competitive inhibitor of 2OG-dependent dioxygenases, suppresses
      the catalytic activity of Tet proteins (W Xu et al. 2011).Both fully methylated and
      hemimethylated DNA in a CG or non-CG context can serve as substrates for TET1 (Tahiliani et
      al. 2009; Ficz et al. 2011; Pastor et al. 2011). In tumor cells, the normal pattern of DNA
      methylation is often altered, resulting in global hypomethylation of the genome in
      conjunction with hypermethylation at CpG islands within the promoters of critical genes such
      as tumor suppressors (Esteller, 2008).

      The TET1 gene, was initially identified in acute myeloid leukemia (AML) as a fusion partner
      of the histone H3 Lys 4 (H3K4) methyltransferase MLL (mixed-lineage leukemia) (Ono et al.
      2002; Lorsbach et al. 2003). TET1 is significantly upregulated and plays an oncogenic role in
      MLL-rearranged leukemia, rendering TET1 as a potential target for treating this form of
      hematopoietic malignancy ( Huang et al., 2013). Tet1 is abundantly expressed in hematopoietic
      stem/progenitor cells (HSC/HPCs) and differentiated lineages such as B cells and myeloid
      cells (Huang et al., 2013; Li et al., 2011 ; Moran-Crusio et al., 2011)
observational model: Cohort
time perspective: Prospective
measure: expression of TET1 gene in acute leukemia
time frame: baseline
description: role of TET1 gene expression in leukemogenesis
intervention type: Device
intervention name: real time PCR
description: Real Time PCR is based on the detection of the fluorescence produced by a reporter molecule which increases, as the reaction proceeds. These fluorescent reporter molecules include dyes that bind to the double-stranded DNA or sequence specific probes . Moreover, there is no need for the post PCR processing which saves the resources and the time. .
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
last name: Monica Botros
phone: +201069195672
email: monecabotros@yahoo.com
citation: Jain A, Varma S, Garg R, Malhotra P. Unilateral Gynaecomastia in a Young Man with Chronic Myeloid Leukemia. Indian J Hematol Blood Transfus. 2017 Sep;33(3):448-450. doi: 10.1007/s12288-016-0762-z. Epub 2016 Dec 19.
PMID: 28824259
citation: Lee BS, Jan YD, Huang GS, Huang CH, Chou HY, Wang JS, Tseng WY. Effect of dentin bonding agent diffusing through dentin slices on the reactive oxygen species production and apoptosis of pulpal cells. J Formos Med Assoc. 2015 Apr;114(4):339-46. doi: 10.1016/j.jfma.2012.12.009. Epub 2013 Feb 13.
PMID: 25839767
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Monica Botros Mosaad
investigator title: Resident doctor of clinical pathology department South Egypt Cancer Institute
mesh term: Leukemia
mesh term: Acute Disease