title: 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.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Internal Medicine-Hematooncology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Michael
authors.initials: M
authors.lastname: Doubek
authors.forename: Ivo
authors.initials: I
authors.lastname: Palasek
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Pospisil
authors.forename: Marek
authors.initials: M
authors.lastname: Borsky
authors.forename: Martin
authors.initials: M
authors.lastname: Klabusay
authors.forename: Yvona
authors.initials: Y
authors.lastname: Brychtova
authors.forename: Tomas
authors.initials: T
authors.lastname: Jurcek
authors.forename: Ivana
authors.initials: I
authors.lastname: Jeziskova
authors.forename: Marta
authors.initials: M
authors.lastname: Krejci
authors.forename: Dana
authors.initials: D
authors.lastname: Dvorakova
authors.forename: Jiri
authors.initials: J
authors.lastname: Mayer
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D016022:Case-Control Studies; D050676:Core Binding Factor Alpha 2 Subunit / Q000032:analysis; D050658:Core Binding Factor beta Subunit / Q000032:analysis; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis*; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000628:therapy; D012008:Recurrence; D014178:Translocation, Genetic; D025721:WT1 Proteins / Q000032:analysis*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C493692:CBFB protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D050658:Core Binding Factor beta Subunit; D009363:Neoplasm Proteins; C493728:RUNX1 protein, human; D025721:WT1 Proteins; D051788:Myeloid-Lymphoid Leukemia Protein