Chromosomal aneuploidy in leukemic blast crisis: A potential source of error in interpretation of bone marrow engraftment analysis by VNTR amplification

Background: Polymerase chain reaction (PCR) amplification of polymorphic mi crosatellite or minisatellite DNA markers has proven to be a fast, sensitiv e, and specific technique in post-transplantation monitoring of bone marrow engraftment, as well as early detection of residual disease and relapse. D eletion or amplification of chromosomal segments carrying marker loci, as c an occur in leukemia and other hematologic malignancies, may result in loss or increased dosage of marker alleles. Examination of these marker alleles by PCR therefore may give aberrant results, which might lead to misinterpr etation of bone marrow transplantation (BMT) engraftment studies. Methods and Results: We report a case of chronic myelogenous leukemia treat ed by BMT PCR amplification of the minisatellite at the apoB locus on chrom osome 2 was used to monitor the donor bone marrow engraftment. The patient experienced relapse in blast crisis with a near-haploid karyotype with loss of recipient-specific apoB allele causing an aberrant PCR result for bone marrow engraftment that mimicked full donor engraftment. Conclusions: Loss or gain of polymorphic DNA markers because of chromosomal losses or gains in some hematologic malignancies may affect the interpreta tion of bone marrow engraftment studies by PCR. When choosing polymorphic m arkers for such studies, it is important to avoid those that will be affect ed by expected chromosomal alteration, if possible. In addition, any abbera nt post-transplantation typing should prompt further investigation to rule out the possibility of chromosomal aberration. Review of all pertinent labo ratory studies is important to avoid misinterpretation of results from a si ngle test for engraftment analysis.