Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human diagnostic samples from children with NCI high risk B-precursor ALL treated on the protocol COG 1961 to investigate early response and outcome in high-risk childhood acute lymphoblastic leukemia

ABSTRACT: The cure rate for childhood ALL has improved considerably in part because therapy is routinely tailored to the predicted risk of relapse. Various clinical and laboratory variables are used in current risk-stratification schemes, but many children who fail therapy lack adverse prognostic factors at initial diagnosis. Using gene expression analysis, we have identified genes and pathways in a NCI high-risk childhood B-precursor ALL cohort at diagnosis that may play a role in early blast regression as correlated with the Day 7 marrow status. We have also identified a 47-probeset signature (representing 41 unique genes) that was predictive of long term outcome in our dataset as well as three large independent datasets of childhood ALL treated on different protocols. Experiment Overall Design: Diagnostic marrow samples from 99 children with NCI high risk B-precursor ALL treated on the protocol COG 1961 were analyzed. To study genetic profiles associated with early response to therapy, 82 of the total 99 patients were analyzed: 42 patients with a M1 marrow at day 7 of therapy were compared to 40 patients with a M3 marrow at day 7. To study the genes associated with long-term outcome, expression profiles of 59 (of the total 99) patients were analyzed: 28 patients who remained in complete continuous remission (CCR) for at least 4 years and 31 patients who suffered a bone marrow relapse within the first 3 years of initial diagnosis. Forty-two patients were common in both the early response and outcome analyses.

ORGANISM(S): Homo sapiens

SUBMITTER: Deepa Bhojwani

PROVIDER: E-GEOD-7440 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression signatures predictive of early response and outcome in high-risk childhood acute lymphoblastic leukemia: A Children's Oncology Group Study [corrected].

Bhojwani Deepa D Kang Huining H Menezes Renee X RX Yang Wenjian W Sather Harland H Moskowitz Naomi P NP Min Dong-Joon DJ Potter Jeffrey W JW Harvey Richard R Hunger Stephen P SP Seibel Nita N Raetz Elizabeth A EA Pieters Rob R Horstmann Martin A MA Relling Mary V MV den Boer Monique L ML Willman Cheryl L CL Carroll William L WL

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20080901 27

<h4>Purpose</h4>To identify children with acute lymphoblastic leukemia (ALL) at initial diagnosis who are at risk for inferior response to therapy by using molecular signatures.<h4>Patients and methods</h4>Gene expression profiles were generated from bone marrow blasts at initial diagnosis from a cohort of 99 children with National Cancer Institute-defined high-risk ALL who were treated uniformly on the Children's Oncology Group (COG) 1961 study. For prediction of early response, genes that corr ...[more]

PMID: 18802149

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Project description:Background. B-Acute lymphoblastic leukemia (B-ALL) represents a hematologic malignancy with poor clinical outcome and low survival rates in adult patients. Only 61% of Colombian adult patients with ALL achieve complete remission and a median overall survival of less than 11.3 months and event-free survival of 7.34 months. Identification of prognostic factors is crucial for proper treatment strategies and optimal results of therapy. The goal of our study was to determine if gene expression signatures correlate with response to therapy and to evaluate the utility of these as prognostic tools for survival to better predict patient risk prior to therapy. Methods and findings. This study included 43 adult patients newly diagnosed with B-cell precursor or common B-ALL. Through microarray gene expression profiles, we identified 442 genes differentially expressed between 27 leukemia patients who responded or not to induction chemotherapeutic treatment. Hierarchical analysis with the 99 most differentially expressed genes between the two groups revealed 3 sets of patients that differed in their clinical characteristics, giving these genes high prognostic clinical outcome impact. We validated the expression of 7 genes by RT-PCR in 43 patients, and in addition to finding a correlation with gene expression profiles, we established correlations with good and poor prognosis from the time of diagnosis. Conclusions. Our study suggests that the response to induction treatment and clinical outcome of patients can be predicted from the onset of the disease and that gene expression profiles can be used to stratify patient risk adequately and accurately. The present study represents the first that shows that gene expression profiling could become a clinically relevant tool for stratification in the early course of disease of Colombian adults B-ALL. Stem cells from bone marrow samples from B-acute lymphoblastic leukemia (B-ALL) patients responding or not to the inductive therapy were isolated by sorting, and the gene expression was compared between the two groups. This submission includes samples from 27 B-ALL patients and 3 healthy individuals.

Dataset Information

Transcription profiling of human diagnostic samples from children with NCI high risk B-precursor ALL treated on the protocol COG 1961 to investigate early response and outcome in high-risk childhood acute lymphoblastic leukemia

Publications

Gene expression signatures predictive of early response and outcome in high-risk childhood acute lymphoblastic leukemia: A Children's Oncology Group Study [corrected].

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