Advertisement

Topics

Genome-wide Single Nucleotide Polymorphism (SNP) Array-based Approach to Predict Chemoresponse and Survival in Patients With Acute Lymphoblastic Leukemia

2014-08-27 03:15:30 | BioPortfolio

Summary

Acute lymphoblastic leukemia (ALL) is not a single disease, but a composite of heterogeneous subgroup. Accordingly, more sophisticated classification in ALL is essential to achieve further improvement of treatment outcomes. However, only a few genetic markers are revealed to have significant prognostic implications in ALL patients. The current study is designed to stratify the ALL patients according to their prognosis and to predict their outcomes by a pharmacogenetic approach. A predictive model will be generated from 130 genotypes in adult ALL patients diagnosed at the Samsung Medical Center (SMC), Sungkyunkwan University School of Medicine, Seoul,Korea between 1994 and 2008. The validation of the predictive model will be performed using an independent external cohort of ALL patients.

1. Definition of the cohort: two hundred ALL patients from the SMC as a test set, another 100 patients from the SMC as a first validation set, and another 150 independent external patients as second external validation set. DNAs will be extracted and stored from patients' samples collected at the time of diagnosis.

2. In the test set, genotypes will be determined using a MALDI-TOF based platform (Sequenom, San Diego, CA, USA) for 130 SNPs of the candidate genes involved in DNA repair pathway, drug metabolism/transport pathway and folate metabolism pathway.

3. Bioinformatic analyses will be performed to identify around 13 genotypes (10%) having strongest predictive significance out of these 130 SNPs in terms of their treatment outcomes, drug toxicity and prognosis in the test set.

4. These 13 genotypes will be validated in the first cohort of 100 ALL patients using a multivariate Cox's proportional hazard model.

5. The predictive model will be built up based on Cox's proportional hazard model derived from 13 candidate genotypes and clinical risk factors.

6. The predictive model based on pharmacogenetic information will be validated again in the second, independent external cohort of 150 ALL patients.

Definite prognostic value was not established for genetic or molecular markers in acute lymphoblastic leukemia (ALL) except BCR/ABL fusion gene. The current study attempts to build up a predictive model based on single nucleotide polymorphisms (SNPs) with pharmacogenetic approach using 130 genotypes in the multiple candidate pathways such as DNA repair pathway, drug metabolism / transport pathway and folate metabolism pathway. The predictive model based on SNPs will be generated and validated with respect to treatment outcomes, drug toxicity and prognosis in adult ALL patients.

The present study will demonstrate that: 1) Pharmacogenetic information derived from SNPs involved in the DNA repair pathway, drug metabolism/transport pathway and folate metabolism pathway, is helpful to predict the treatment outcomes, drug toxicity and prognosis in ALL patients; 2) Predictive model derived from pharmacogenetic information will be effective and reasonable approach to stratify ALL patients according to their clinical outcomes; 3) The SNP-based predictive model could be reasonably applied to the treatment of ALL patients, thus becoming a basis for further improvement of treatment outcome; 4) Finally, this project will enhance and facilitate the pharmacogenetic research in the hematology area, thus make the team to lead the pharmacogenetic research in the world.

Study Design

Observational Model: Case-Only, Time Perspective: Retrospective

Conditions

Acute Lymphoblastic Leukemia

Location

Samsung Medical Center
Seoul
Korea, Republic of
135-710

Status

Recruiting

Source

Samsung Medical Center

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:15:30-0400

Clinical Trials [1954 Associated Clinical Trials listed on BioPortfolio]

Diagnostic Study of Patients With Acute Lymphoblastic Leukemia or Acute Promyelocytic Leukemia

RATIONALE: Determination of genetic markers for acute lymphoblastic leukemia and acute promyelocytic leukemia may help identify patients with this disease and help predict the outcome of t...

The Expression of CD 95, CD20, CD34 and CD44 in Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia , also known as acute lymphocytic leukemia, characterized by the overproduction and accumulation of cancerous, immature white blood cells, known as lymphoblast...

Phase II Study of Clofarabine in Pediatric Acute Lymphoblastic Leukemia (ALL)

Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed acute lymphoblastic leukemia (ALL) who...

Palbociclib and Dexamethasone in Treating Participants With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

This phase I trial studies the side effects and best dose of palbociclib when given together with dexamethasone in treating participants with B-cell acute lymphoblastic leukemia that has c...

Genomic Changes in Childhood Acute Lymphoblastic Leukemia

To study the genomics with cell cycle and lymphocyte differentiation in disease, remission and relapse of childhood acute lymphoblastic leukemia. Then correlate these data with age, white ...

PubMed Articles [6644 Associated PubMed Articles listed on BioPortfolio]

Concurrent Acute Myelofibrosis and Acute Lymphoblastic Leukemia in Childhood: Case Report and Review of the Literature.

Myelofibrosis is associated with a wide variety of neoplastic and non-neoplastic bone marrow diseases, predominately myeloproliferative neoplasms and acute myeloid leukemia. The following case documen...

Treating Adult Acute Lymphoblastic Leukemia in Brazil-Increased Early Mortality Using a German Multicenter Acute Lymphoblastic Leukemia-based regimen.

Acute lymphoblastic leukemia (ALL) in adults is an invariably aggressive and rare disease. Its treatment is based on the use of multidrug regimens, which have been improved since the 1970s. Few publis...

CD9 expression indicates a poor outcome in acute lymphoblastic leukemia.

We undertook a single-center retrospective study to determine the relationship between CD9 and acute lymphoblastic leukemia (ALL).

Toxicity of Vincristine Combined With Posaconazole in Children With Acute Lymphoblastic Leukemia.

Vincristine (VCR) is one of the main drugs of acute lymphoblastic leukemia (ALL) treatment. Azole antifungal medications are used for treatment or prophylaxis of invasive fungal infections in acute le...

Acquired Hypofibrinogenemia Before Asparaginase Exposure During Induction Therapy for Pediatric Acute Lymphoblastic Leukemia: A Report of 2 Cases and Review of the Literature.

Coagulopathy in pediatric leukemia patients is typically associated with acute promyelocytic leukemia or after asparaginase use in acute lymphoblastic leukemia. Rarely seen in acute lymphoblastic leuk...

Medical and Biotech [MESH] Definitions

A tyrosine kinase inhibitor and ANTINEOPLASTIC AGENT that inhibits the BCR-ABL kinase created by chromosome rearrangements in CHRONIC MYELOID LEUKEMIA and ACUTE LYMPHOBLASTIC LEUKEMIA, as well as PDG-derived tyrosine kinases that are overexpressed in gastrointestinal stromal tumors.

A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)

Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.

A leukemia/lymphoma found predominately in children and adolescents and characterized by a high number of lymphoblasts and solid tumor lesions. Frequent sites involve LYMPH NODES, skin, and bones. It most commonly presents as leukemia.

A rare acute myeloid leukemia characterized by abnormal EOSINOPHILS in the bone marrow.

More From BioPortfolio on "Genome-wide Single Nucleotide Polymorphism (SNP) Array-based Approach to Predict Chemoresponse and Survival in Patients With Acute Lymphoblastic Leukemia"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Pharmacy
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...


Searches Linking to this Trial