The association between severe aplastic anemia (AA) and DR2 antigen seems to be well established. However, since discrimination between two DR2-associated splits, namely DR15 and DR16, rarely was performed, it remains unclear whether one or both of these subvariants are responsible for AA susceptibility. In this study, we have analyzed the HLA-DR allelic distribution in a group of 37 AA patients of slavic origin from North-Western Russia. The experimental design included PCR-based amplification of DRB-specific sequences, followed by reverse dot-blot hybridization of the biotinylated PCR-product with the set of sequence-specific oligonucleotide probes. HLA-DRB alleles were identified by non-radioactive enzymatic reaction, then standard serological specificities of HLA-DR antigen were estimated according to the WHO nomenclature. Whereas DR15 subtype occurred more often in the patients (23.0% vs. 13.3%, p< 0.05), DR16 split did not show the same tendency. The results, show the overall predominance of HLA-DR2 specificity (DR15+DR16) did not reach statistical significance (24.4% vs.17.5%, p<0.2). Thus, we conclude that repeatedly reported DR2 frequency increase in AA patients is mainly attributed to the prevalence of DR15 subtype.
There are few data on different biological significance of b2a2 and b3a2 transcripts. The main one is thrombocytosis in b3a2 CML patients (R.A.Perego e.a.,2000), probably associated with coexpression of m-bcr-abl (T.Liu e.a.,2006). Noteworthy that the level of transcripts in primary CML patients did not differ(Rodrigues J. e.a.,2005). That was the reason for evaluating Glivec efficacy in CP CML patients with bcr-abl trabscripts- b2a2 and b3a2.
Patients and Methods. 97 Ph+, CP CML patients were studied. They received Glivec either as front line therapy or after resistance to preceeding therapy. Analysis of b3a2 and b2a2 transcripts was performed in 27 of them. Cytogenetics was performed routine technology with G-banding. Statitics: Kaplan-Meier survival analysis and Cox regression model were used.
Results. The median time to CCyR in whole cohort of patients was 320 days. Of 27 bcr-abl studied patients, 9 had b2a2 and 18 b3a3 transcripts. They did not differ in age, duration of the disease and Sokal Score. Median time to CCyR in b2a2 patients was 172 days and 362 in b3a2 patients(p=.0001). Time to CCyR was shorter in b2a2 patients(p=.003) and insignificantly longer in b3a2 patients when compared to the whole cohort of studied patients. Cox analysis revealed that type of transcripts is independant prognostic factor, including platelet level and spleen size. Difference was more pronounced in patients with front line Glivec therapy.
Conclusion. b2a2 transcript is independent prognostic marker for early achievement of CCyR on Glivec therapy.
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