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.
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.
Doubek
Michael
M
Department of Internal Medicine-Hematooncology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Palasek
Ivo
I
Pospisil
Zdenek
Z
Borsky
Marek
M
Klabusay
Martin
M
Brychtova
Yvona
Y
Jurcek
Tomas
T
Jeziskova
Ivana
I
Krejci
Marta
M
Dvorakova
Dana
D
Mayer
Jiri
J
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
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