ABSTRACT
AIMS: Asparaginase (ASP) hypersensitivity is a well-known challenge in the treatment of lymphoblastic malignancies. In terms of cost considerations, the cheap native Escherichia coli ASP, the most immunogenic form of this medication, is used in the first line in middle-income countries. Previously, the role of the HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02 haplotype had been established to associate with E. coli ASP hypersensitivity. We investigated a possible cost-effective genetic testing method to identify patients harbouring the risk HLA haplotype in order to pave the way for safer ASP treatment. METHODS: In 241 patients with previously determined HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02 haplotype and known ASP hypersensitivity status, 4 candidate HLA-tagging single-nucleotide polymorphisms (SNP)s were measured, and the performance of the different sets of these tag SNPs was evaluated. RESULTS: We identified a combination of 2 SNPs - rs28383172 and rs7775228 - as a tag for HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02 haplotype with sensitivity and specificity values >95%. In line with previous findings, we found complete concordance between HLA-DRB1*07:01 and rs28383172. With bioinformatics methods, the results were also confirmed in the 1000 Genomes dataset in different ethnic groups. CONCLUSION: Rs28383172 and rs7775228 are suitable for identifying HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02 carriers. Compared to the rest of the population, patients with hypersensitivity-prone genotype would benefit more from the administration of less immunogenic PEGylated ASP before the hypersensitivity evolves, incurring minimal extra cost.
Subject(s)
Asparaginase , Drug Hypersensitivity , HLA-DRB1 Chains , Humans , Alleles , Asparaginase/adverse effects , Drug Hypersensitivity/genetics , Escherichia coli , Gene Frequency , Genetic Predisposition to Disease , Haplotypes , HLA-DQ alpha-Chains/genetics , HLA-DQ beta-Chains/genetics , HLA-DRB1 Chains/genetics , Polymorphism, Single NucleotideABSTRACT
Extracellular vesicles are produced in all organisms. The most intensively investigated categories of extracellular vesicles include apoptotic bodies, microvesicles and exosomes. Among a very wide range of areas, their role has been confirmed in intercellular communication, immune response and angiogenesis (in both physiological and pathological conditions). Their alterations suggest the potential use of them as biomarkers. In this paper the authors give an insight into the research of extracellular vesicles in general, and then focus on published findings in hematological malignancies. Quantitative and qualitative changes of microvesicles and exosomes may have value in diagnostics, prognostics and minimal residual disease monitoring of hematological malignancies. The function of extracellular vesicles in downregulation of natural killer cells' activity has been demonstrated in acute myeloid leukemia. In chronic lymphocytic leukemia, microvesicles seem to play a role in drug resistance. Orv. Hetil., 2016, 157(35), 1379-1384.
