RESUMEN
Several genes involved in the pathogenesis have been identified, with the human leukocyte antigen (HLA) system playing an essential role. However, the relationship between HLA and a cluster of hematological diseases has received little attention in China. Blood samples (n = 123913) from 43568 patients and 80345 individuals without known pathology were genotyped for HLA class I and II using sequencing-based typing. We discovered that HLA-A*11:01, B*40:01, C*01:02, DQB1*03:01, and DRB1*09:01 were prevalent in China. Furthermore, three high-frequency alleles (DQB1*03:01, DQB1*06:02, and DRB1*15:01) were found to be hazardous in malignant hematologic diseases when compared to controls. In addition, for benign hematologic disorders, 7 high-frequency risk alleles (A*01:01, B*46:01, C*01:02, DQB1*03:03, DQB1*05:02, DRB1*09:01, and DRB1*14:54) and 8 high-frequency susceptible genotypes (A*11:01-A*11:01, B*46:01-B*58:01, B*46:01-B*46:01, C*01:02-C*03:04, DQB1*03:01-DQB1*05:02, DQB1*03:03-DQB1*06:01, DRB1*09:01-DRB1*15:01, and DRB1*14:54-DRB1*15:01) were observed. To summarize, our findings indicate the association between HLA alleles/genotypes and a variety of hematological disorders, which is critical for disease surveillance.
Asunto(s)
Enfermedades Hematológicas , Antígenos de Histocompatibilidad Clase I , Humanos , Frecuencia de los Genes , Alelos , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Genotipo , Antígenos de Histocompatibilidad Clase I/genética , Enfermedades Hematológicas/genética , Haplotipos , Predisposición Genética a la EnfermedadRESUMEN
OBJECTIVE: To establish a new digital polymerase chain reaction (dPCR) system for the detection of BCR-ABL fusion gene in patients with chronic myeloid leukemia (CML), and explore its analytical performance and clinical applicability in the detection of BCR-ABLp190/210/230. METHODS: A new dPCR system for detecting BCR-ABLp190/210/230 was successfully developed, and its sensitivity difference with qPCR and improvement of drug side effects in patients with CML during drug reduction or withdrawal were compared. RESULTS: Among 176 samples, qPCR and dPCR showed high consistency in the sensitivity of detecting BCR-ABL (82.39%), and the positive rate of dPCR was about 5 times higher that of qPCR (20.45% vs 3.98%). During follow-up, blood routine (25% vs 10%), kidney/liver/stomach (25% vs 20%) and cardiac function (10% vs 0) were significantly improved after drug reduction or withdrawal in patients with initial dPCR negative compared with before drug reduction or withdrawal. CONCLUSIONS: This new dPCR detection system can be applied to the detection of BCR-ABLp190/210/230. It has better consistency and higher positive detection rate than qPCR. Drug withdrawal or dose reduction guided by dPCR has a certain effect on improving drug side effects.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Leucemia Mielógena Crónica BCR-ABL Positiva , Humanos , Proteínas de Fusión bcr-abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Reacción en Cadena de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The function of natural killer (NK) cells has previously been implicated in hematopoietic-related diseases. Killer immunoglobulin-like receptors (KIR) play an important role in NK cells after hematopoietic stem cell transplantation. To explore the immunogenetic predisposition of hematological-related diseases, herein, a multi-center retrospective study in China was conducted, analyzing and comparing 2519 patients with hematopathy (mainly, acute lymphoblastic leukemia, acute myeloid leukemia, aplastic anemia, and myelodysplastic syndrome) to 18,108 individuals without known pathology. Genotyping was performed by polymerase chain reaction with specific sequence primers (PCR-SSP). As a result, we discovered four genes including KIR2DL5 (OR: 0.74, 95% CI 0.59-0.93; Pc = 0.0405), 2DS1 (OR: 0.74, 95% CI 0.59-0.93; Pc = 0.0405), 2DS3 (OR: 0.58, 95% CI 0.41-0.81; Pc = 0.0180), and 3DS1 (OR: 0.74, 95% CI 0.58-0.94; Pc = 0.0405) to be protective factors that significantly reduce the risk of aplastic anemia. Our findings offer new approaches to immunotherapy for hematological-related diseases. As these therapies mature, they are promising to be used alone or in combination with current treatments to help to make blood disorders a manageable disease.
Asunto(s)
Anemia Aplásica , Enfermedades Hematológicas , Humanos , Estudios Retrospectivos , Anemia Aplásica/genética , Pueblos del Este de Asia , Receptores KIR/genética , Genotipo , Enfermedades Hematológicas/genética , Frecuencia de los GenesRESUMEN
HLA-B*44:03:67 differs from HLA-B*44:03:02:01 by one nucleotide in exon 4.
Asunto(s)
Antígenos HLA-B , Humanos , Alelos , Pueblos del Este de Asia/genética , Antígenos HLA-B/genética , Nucleótidos , Análisis de Secuencia de ADNRESUMEN
Mastering the SNP content in the HLA region can be based on it to judiciously select unrelated donor stem cells with preferable MHC matching to lower postoperative complications. Herein, quantitative PCR-based primers and probes were designed for 10 transplants outcome-associated SNP loci with two-allelic polymorphism, and then a new detection system ("HLA-10-SNP") was established. Compared with Sanger sequencing, its accuracy has been proven to reach 100%. Additionally, fluorescent PCR typing of 10 important SNPs via this system expressed excellent repeatability (sensitivity, 20 ng). Overall, the new system achieves single-sample classification precision and easily distinguishable results, equipped with the advantages of simple, rapid, accurate, and effective, promising to acquire widespread popularization and application in clinical settings.