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
| Authors | |
|---|---|
| Year of publication | 2009 |
| Type | Article in Periodical |
| Magazine / Source | Experimental Hematology |
| MU Faculty or unit | |
| Citation | |
| Field | Oncology and hematology |
| Keywords | acute myeloid leukemia - minimal residual disease - molecular relapse - treatment |
| Description | Objective. Our hypothesis was that by frequent monitoring the minimal residual disease (MRD) in different compartments (peripheral blood, PB; bone marrow, BM; CD34+BM cells; and CD34-BM cells), we would be able to find patterns which could predict a clinical relapse of acute myeloid leukemia (AML) and discover whether it is possible to treat the disease in the phase of molecular relapse. Methods. In our cohort of patients, frequent MRD monitoring was performed in all phases of AML treatment using RQ PCR for fusion transcripts (CBFB/MYH11, RUNX1/RUNX1T1, fusion transcripts of MLL gene) and for the WT1 gene. In 79 AML patients and 6 healthy volunteers, 2664 samples were examined. Results. We found a strong correlation between the fusion transcripts levels in BM and PB. The correlation between WT1 PB and BM levels was far less satisfactory. We were not able to ascertain any WT1 level as a confidential marker of molecular remission in either compartment. In relapsed patients, the time period of molecular to hematological relapse was 8–79 days. In the case of molecular relapse, the highest levels of fusion transcripts were in the CD34+BM cells. Twelve patients were treated for 21 molecular relapses; two-thirds of the patient had favorable treatment response. Conclusion. Frequent quantitative monitoring of fusion transcripts (in contrast to WT1) is useful for a reliable prediction of hematological relapse in AML patients. The treatment of molecular relapse of AML may be successful. |
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