Drug-Response Signature Predicts Outcome in Adult Acute Myeloid Leukemia and Associates Poor Response with Molecular Characteristics of Hematopoietic Stem Cells
العنوان: | Drug-Response Signature Predicts Outcome in Adult Acute Myeloid Leukemia and Associates Poor Response with Molecular Characteristics of Hematopoietic Stem Cells |
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المؤلفون: | Luzie U. Wingen, Michael Heuser, Hartmut Döhner, Gunnar Cario, Marcel Tauscher, Doris Steinemann, Lars Bullinger, Nils von Neuhoff, Arnold Ganser, Brigitte Schlegelberger |
المصدر: | Blood. 104:2024-2024 |
بيانات النشر: | American Society of Hematology, 2004. |
سنة النشر: | 2004 |
مصطلحات موضوعية: | Oncology, medicine.medical_specialty, Immunology, CD34, Induction chemotherapy, Myeloid leukemia, Adult Acute Myeloid Leukemia, Cell Biology, Hematology, Drug resistance, Biology, Biochemistry, Haematopoiesis, Internal medicine, medicine, Stem cell, Progenitor cell |
الوصف: | Resistance to induction chemotherapy is of independent prognostic value in acute myeloid leukemia (AML). DNA microarrays were used to determine the gene-expression profile of AML blasts in 38 patients with good or poor response to induction chemotherapy. We selected an 11-sample training set, applying prediction analysis of microarrays (PAM) to devise a drug-response predictor which was tested on the remaining 27 samples and an independent set of samples recently published (Bullinger et al. 2004). Our drug-response predictor with 46 clones divided the 27 samples into two prognostic subgroups, the poor response group having a significantly shorter overall survival (P= .021). A subset of these 46 clones was sufficient to divide the published 62-sample test-set with intermediate risk cytogenetics into prognostically relevant subgroups (P= .028), adding prognostic information to that of known risk factors in multivariate analysis (hazard ratio, 2.8; 95 percent confidence interval, 1.4 to 5.8; P= .005). Thirteen of 39 drug resistance-enriched genes are known to be upregulated in hematopoietic stem/progenitor cells, and the expression pattern in normal CD34+ cells is highly correlated to the drug-resistance signature. This suggests that drug resistant AMLs show molecular features of hematopoietic stem/progenitor cells and can be identified by a characteristic gene-expression profile. |
تدمد: | 1528-0020 0006-4971 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::e26ce86b1e28198c9aa4f2830bb6b9feTest https://doi.org/10.1182/blood.v104.11.2024.2024Test |
رقم الانضمام: | edsair.doi...........e26ce86b1e28198c9aa4f2830bb6b9fe |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15280020 00064971 |
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