Detection of CBFbeta/MYH11 fusion transcripts in patients with inv(16) acute myeloid leukemia after allogeneic bone marrow or peripheral blood progenitor cell transplantation.
We evaluated the occurrence of the CBFbeta/MYH11 fusion transcripts by PCR analysis in 10 patients with inv(16)(p13;q22) acute myeloid leukemia (AML) who underwent allogeneic bone marrow transplantation (BMT) (n = 5), peripheral blood progenitor cell transplantation (PBPCT) (n = 3), or autologous transplantation (n = 2). In addition to the analysis of minimal residual disease (MRD), the chimerism status of patients after allogeneic transplant was studied by PCR. The CBFbeta/MYH11 fusion transcript was not detectable in six of seven patients who remained in remission after allogeneic BMT or PBPCT. Two of these patients in remission were monitored for 50 months and 64 months post-BMT. One patient in remission was PCR-positive for CBFbeta 3 months post-BMT in a single BM sample, but not in a simultaneously examined blood sample, suggesting that analyses from BM samples are more sensitive than those from blood samples. Sequential PCR assays performed 6 and 12 months post-BMT obtained from the same patient were negative. Another patient with a positive PCR assay 3 months post-allogeneic PBPCT, remained PCR positive for the CBFbeta/MYH11 fusion transcript when tested 6 months post-PBPCT. A chimerism analysis by PCR revealed a mixed chimerism status in this patient. He relapsed 7 months post-transplant. Before transplant, in all nine patients who were in complete remission of AML (eight patients in 1CR, one patient in 2CR), the CBFbeta/MYH11 transcript was detectable. In one patient in relapse, the fusion transcript was not only detectable in blood and bone marrow, but also in a cerebrospinal fluid sample prior to transplant. Two patients who received autologous BMT were monitored for CBFbeta/MYH11 transcripts 3 months after BMT. The CBFbeta/MYH11 was detected in these patients. Both patients subsequently relapsed 3 months and 23 months post-autologous BMT. The results study show that analysis of the CBFbeta/MYH11 fusion transcript by PCR seems to be a suitable method for monitoring minimal residual disease in AML patients with inv (16).
Elmaagacli
A H
AH
Department of Bone Marrow Transplantation, University Hospital of Essen, Germany.
Beelen
D W
DW
Kroll
M
M
Trzensky
S
S
Stein
C
C
Schaefer
U W
UW
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D016026:Bone Marrow Transplantation; D002678:Chimera / Q000235:genetics; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000628:therapy*; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000706:statistics & numerical data; D012680:Sensitivity and Specificity; D013997:Time Factors; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
C095514:CBFbeta-MYH11 fusion protein; D017931:DNA Primers; D015514:Oncogene Proteins, Fusion