title: Short tandem repeat and human leukocyte antigen mutations or losses confound engraftment and typing analysis in hematopoietic stem cell transplants.
abstract: Clonal chromosomal abnormalities are often found in the tumor cells of patients with malignancies. These abnormalities can cause downregulation of human leukocyte antigen (HLA) and instability of short tandem repeat (STR) DNA sequences, confounding HLA typing and/or engraftment analysis in hematopoietic stem cell transplants (HSCT). We describe here the abnormalities observed during testing of 600 HSCT patients. HLA molecular typing was performed by reference strand conformational analyses and/or sequence-based typing. STR testing was performed with 10 to 16 STR primer sets, following 1 to 4 informative loci in each patient. Eight patients exhibited either loss of heterozygosity (4 STR, 3 HLA) or STR length mutation (n = 1), and 5 of the 8 exhibited correlative cytogenetic abnormalities. Diagnoses were acute myelogenous leukemia (AML; n = 7) or myelofibrosis (MFIB: n = 1), yielding an 11% incidence of these chromosomal abnormalities among the subset of 72 AML/MFIB HSCT patients. These results highlight some of the problems encountered and the possibility for interpretive errors that can arise when analyzing molecular typing and engraftment data, particularly among AML/MFIB patients.
authors.affiliation: Clinical Research Division, Department of Laboratory Medicine, University of Washington, Seattle, WA 98109, USA. spereira@seattlecca.org
authors.forename: Shalini
authors.initials: S
authors.lastname: Pereira
authors.forename: Tamara
authors.initials: T
authors.lastname: Vayntrub
authors.forename: Debra D
authors.initials: DD
authors.lastname: Hiraki
authors.forename: Athena M
authors.initials: AM
authors.lastname: Cherry
authors.forename: Sally
authors.initials: S
authors.lastname: Arai
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Dvorak
authors.forename: F Carl
authors.initials: FC
authors.lastname: Grumet
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations / Q000706:statistics & numerical data; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D023001:Transplantation Tolerance / Q000235:genetics
chemical_list: D006680:HLA Antigens