#9
HLA TYPE CHANGE IN A PATIENT WITH ACUTE LYMPHOBLASTIC LEUKAEMIA (ALL).
David Briggs PhD 1, Shirley Jobson PhD 1, Mike Griffiths BSc 2, Pat Taylor BSc 1 and Sarah Lawson MB, ChB 3. 1 H&I, National Blood Service, Birmingham, W Midlands, United Kingdom ; 2 Regional Genetics Laboratory, Birmingham Womens Hospital, Birmingham, W Midlands, United Kingdom and 3 Department of Haematology, Birmingham Childrens Hospital, Birmingham, W Midlands, United Kingdom .
Confirmatory HLA typing of HSCT donors and recipients before transplantation is an identitiy check; we do not normally expect a person
s HLA type to change. Our methodology has one potential flaw in that we only test a part, one tissue, of the patient; as that tissue can be subject to genomic instability we could detect a wrong HLA type.
A patient with ALL and mother were HLA typed by SSP-PCR (patient also sequenced) on DNA extracted from blood taken at the end of August 04. A sample of bone marrow had been taken one week before this for karyotyping: 10 cells were examined from unstimulated cells. Blood samples were taken in October 04 for confirmatory HLA typing.
In August the patients HLA type was homozygous for all loci, inherited from his mother. In October, after treatment and in haematological remission the patients HLA type was found to be heterozygous.
An explantion for this was found in the genetic lesion at presentation. At that time the marrow cells showed a near haploid karyotype of 28 chromosomes: one copy of each autosome was lost (including chr6) with the exception of chr 8, 10, 18, and 21. FISH analysis indicated about 90% of the marrow cells were blasts of this type and iIt appears that these cells contained only the maternal HLA haplotype. After treatment it would seem that normal cells predominated in the blood allowing detection of both HLA haplotypes. Hypoploidy is a rare feature of ALL but it might be wise to check the karyotpe of apparently HLA homozygous patients and/or retype using DNA from non-blood cells.