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Molecular characterization of very early relapsed childhood ALL

ABSTRACT: Purpose: In childhood acute lymphoblastic leukemia (ALL), approximately 25% of patients suffer from relapse. In recurrent disease, despite intensified therapy, overall cure rates of 40% remain unsatisfactory and survival rates are particularly poor in certain subgroups. The probability of long-term survival after relapse is predicted from well-established prognostic factors, i. e. time and site of relapse, immunophenotype and minimal residual disease. However, the underlying biological determinants of these prognostic factors remain poorly understood. Results: We show here that patients with very early relapse of ALL are characterized by a distinctive gene expression pattern. We identified a set of 83 genes differentially expressed in very early relapsed ALL compared to late relapsed disease. The vast majority of genes was up-regulated and many were late cell cycle genes with a function in mitosis. In addition, samples from patients with very early relapse showed a significant increase in the percentage of S and G/2M phase cells and this correlated well with the expression level of cell cycle genes. Conclusions: Very early relapse of ALL is characterized by an increased proliferative capacity of leukemic blasts and up-regulated mitotic genes. The latter suggests that novel drugs, targeting late cell cycle proteins, might be beneficial for these patients that typically face a dismal prognosis. Keywords: disease state analysis

ORGANISM(S): Homo sapiens

PROVIDER: GSE4698 | GEO | 2006/09/27

SECONDARY ACCESSION(S): PRJNA96749

REPOSITORIES: GEO

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Transcription profiling of human ALL samples from very early relapsed childhood patients

Project description:Purpose: In childhood acute lymphoblastic leukemia (ALL), approximately 25% of patients suffer from relapse. In recurrent disease, despite intensified therapy, overall cure rates of 40% remain unsatisfactory and survival rates are particularly poor in certain subgroups. The probability of long-term survival after relapse is predicted from well-established prognostic factors, i. e. time and site of relapse, immunophenotype and minimal residual disease. However, the underlying biological determinants of these prognostic factors remain poorly understood. Results: We show here that patients with very early relapse of ALL are characterized by a distinctive gene expression pattern. We identified a set of 83 genes differentially expressed in very early relapsed ALL compared to late relapsed disease. The vast majority of genes was up-regulated and many were late cell cycle genes with a function in mitosis. In addition, samples from patients with very early relapse showed a significant increase in the percentage of S and G/2M phase cells and this correlated well with the expression level of cell cycle genes. Conclusions: Very early relapse of ALL is characterized by an increased proliferative capacity of leukemic blasts and up-regulated mitotic genes. The latter suggests that novel drugs, targeting late cell cycle proteins, might be beneficial for these patients that typically face a dismal prognosis. Experiment Overall Design: We performed gene expression profiling on 60 prospectively collected samples of children with first relapse of acute lymphoblastic leukemia enrolled on the relapse trial ALL-REZ BFM 2002 of the Berlin-Frankfurt-Muenster study group.

2008-06-13 | E-GEOD-4698 | biostudies-arrayexpress

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| phs001049 | dbGaP

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