Detection and treatment of molecular relapse in acute myeloid leukemia with RUNX1 (AML1), CBFB, or MLL gene translocations: frequent quantitative monitoring of molecular markers in different compartments and correlation with WT1 gene expression
| Autor: | Martin Klabusay, Ivo Palásek, Marta Krejčí, Marek Borsky, Ivana Jeziskova, Dana Dvorakova, Jiri Mayer, Michael Doubek, Zdenek Pospisil, Yvona Brychtová, Tomáš Jurček |
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| Rok vydání: | 2008 |
| Předmět: |
Acute promyelocytic leukemia
Adult Male Cancer Research Myeloid Neoplasm Residual Gemtuzumab ozogamicin Core Binding Factor beta Subunit Translocation Genetic Fusion gene 03 medical and health sciences Young Adult 0302 clinical medicine Recurrence hemic and lymphatic diseases Genetics medicine Biomarkers Tumor Humans WT1 Proteins Molecular Biology Aged business.industry Myeloid leukemia Cell Biology Hematology Middle Aged medicine.disease Minimal residual disease 3. Good health Neoplasm Proteins Leukemia Leukemia Myeloid Acute medicine.anatomical_structure 030220 oncology & carcinogenesis Case-Control Studies Core Binding Factor Alpha 2 Subunit Cancer research Myeloid-Lymphoid Leukemia Protein Female business 030215 immunology medicine.drug |
| Zdroj: | Experimental hematology. 37(6) |
| ISSN: | 1873-2399 |
| Popis: | Objective Our objective was to determine the value of frequent minimal residual disease (MRD) monitoring in acute myeloid leukemia (AML) as a robust marker of impending relapse, and whether treatment benefits patients during the MRD-positive phase of their disease. Materials and Methods Frequent MRD monitoring was performed in all AML treatment phases using real-time quantitative polymerase chain reaction for fusion transcripts ( CBFB/MYH11; RUNX1/RUNX1T1 fusion transcripts of MLL gene) and for the Wilms' tumor ( WT1 ) gene. A total of 2,664 samples, taken from 79 AML patients and 6 healthy volunteers, were examined. Presence of fusion gene was detected in 25 of 79 examined patients. Results Vast correlation was discovered for fusion transcripts as well as for the WT1 gene between levels in bone marrow (BM), peripheral blood, CD34 + BM cells, and CD34 – BM cells. WT1 expression, however, was usually positive for cases showing fusion transcripts negativity and in healthy volunteers. Moreover, no universal value of the WT1 expression could unequivocally discriminate between remission and relapse. Therefore, detection of molecular relapses relied on fusion transcripts only and was characterized by strong expression in CD34 + cells. Considering relapsed patients, duration from molecular to hematological relapse was 8 to 79 days (median: 25.5 days). Twelve patients were treated (chemotherapy, gemtuzumab ozogamicin, or immunomodulation after allogeneic transplantation) for 21 molecular relapses and 14 responses to treatment were observed. Conclusions Frequent quantitative monitoring of fusion transcripts is useful for reliably predicting hematological relapse in AML patients. Treatment for molecular relapse of AML can be successful. |
| Databáze: | OpenAIRE |
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