#25
THE CASE OF A HOMOZYGOUS HETEROZYGOTE.
Laima Gaidulis MS , Ji-Yao Sun MD and David Senitzer PhD . 1 HLA Laboratory, City of Hope National Medical Center, Duarte, CA, USA .
Reports have demonstrated loss of heterozygosity(LOH) at chromosome 6p in solid tumors. Loss of an HLA haplotype was detected in a leukemic blood sample with 64 % circulating blasts and 74K/ul leukocytes by molecular typing. LR typing of A, B, Cw, DRB1 and DQB1 by rSSOP identified only A*23, B*07,Cw*07, DRB1*15, and DQB1*06. Homozygosity at all 6 loci seemed unusual but sequence-based typing(SBT) also showed a homozygous genotype: A*2301, B*0702, Cw*0702, DRB1*1501, DQB1*0602, and DPB1*0401.Serological results, on a sample drawn one month earlier, showed two alleles at A, B and DRB1 .Our molecular results needed verification. A new specimen,obtained one month after induction chemotherapy typed as A*0301,2301;B*0702,4001; Cw*0304,0702; DRB1*1301,1501;DQB1*0602,0603 and DPB1* 0301,0401 by both rSSOP and SBT.We hypothesized that the patient
s haplotype loss resulted from a partial deletion of Chromosome 6 during the blast crisis.Both parents were typed.The fathers genotype was established as A*1101,2301;B*0702,4001;Cw*0304,0702;DRB1*1302,1501;DQB1*0602;0604 andDPB1*0401/Bl;The mothers as A*0201,0301;B*0702,4001;Cw*0304,0702;DRB1*0901,1301;DQB1*0303,0603.The patient appears to have retained the paternal haplotype; unfortunately, the B and Cw loci were non-informative. STR analysis with 16 unrelated chromosome markers (Identifiler kit, ABI) did not indicate any LOH. Fish analysis with 2 probes to the HLA B region on 6p also did not detect any deletions involving the 6p21.3-6p22.3 chromosome region. Other mechanisms, not detected by these analyses, may be responsible for the loss of the maternal haplotype. This case illustrates the difficulty in typing patients in blast crisis.