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МАТЕРИАЛЫ КОНФЕРЕНЦИИ
достоверны. В общей группе пациентов при сероне-гативном РА установлено статистически достоверное снижение частоты HLA-DRB1*13 (р<0,05). Этот показатель снижен и при серопозитивном артрите (11,1%) по сравнению с контролем (24,4%), но различия статистически недостоверны. Кроме того, достоверно (р<0,05) снижена частота группы аллелей ША^В1*11 в общей когорте больных (14,6%) и при серонегативном РА, по сравнению с контролем
(28,5%).
Таким образом, установлено, что для жителей Ростовской области иммуногенетическим фактором, ассоциированным с развитием РА, HLA-DRB1*04, протективными факторами в отношении развития этого заболевания являются группы аллелей НЬА-DRB1*11 и ША^В1*13.
Hovhannisyan A., Madelian V., Avagyan S., Nazaretyan M., Mayilyan K., Yepiskoposyan L., Hyussyan A., Sirunyan A., Arakelyan R., Manukyan Z., Jordan F.
GENETIC LIABILITY OF HLA-C*04:01 ALLELE FOR SEVERITY OF COVID-19 IN
ARMENIAN POPULATION
Institute of Molecular Biology, National Academy of Sciences, Yerevan, Armenian Armenian Bone Marrow Donor Registry, Yerevan, Armenia
The novel coronavirus (SARS-CoV-2) infection has recently emerged and become a global health concern causing COVID-19 pandemic.
While some COVID-19 patients suffer rather mild or even no symptoms, others may develop severe respiratory complications. Understanding how variation in HLA is related to the COVID-19 clinical manifestation could help clinicians to identify patients who are likely to progress to severe disease outcomes. However, yet little is known about the potential link between HLA alleles and COVID-19 clinical course.
We aimed to identify associations between common HLA alleles and COVID-19 severity in the Armenian population. A total of 299 COVID-19 patients were classified into three groups according to the disease severity.
Typing for class I and II classical HLA genes was performed using Next-Generation Sequencing (NGS).
For contextualization of the HLA-allele contribution to COVID-19 severity, the data of 5,328 individuals from
the general Armenian population were used.
Patients were further classified into three groups according to the disease symptoms. In the severe disease subgroup of patients (n=122) were those who required critical care such as ICU or ventilator.
The mild disease group (n=102) included patients who were hospitalized but not required ventilators or ICU care, or those recuperating at home.
The asymptomatic group (n=75) consisted of subjects with no symptoms, but who have tested positive for the virus.
We found that the allelic-load of HLA-C*04:01 was associated with a significant increase in severity of COVID-19 clinical manifestations and advanced age of the patients.
Nevertheless, the link between genotype and age was secondary to the former, a much stronger association. Thus, our findings underscore a plausible role of HLA molecules in the clinical manifestation of the COVID-19 infection.
Blau Olga, Blau Igor-Wolfgang
IMPACT OF MOLECULAR GENETIC STUDIES IN ALLOGENEIC STEM CELL TRANSPLANTATION IN AML PATIENTS
Charité University Berlin, Clinic for Hematology, Oncology and Tumorimmunology, Berlin Germany
Acute myeloid leukemia (AML) is a heterogeneous disease with very different disease biology and response to conventional treatments. Achieving complete remission (CR) with complete hematological recovery gives better long-term results than morphological remission with or without incomplete recovery of peripheral blood parameters. Among patients who achieve only morphological remission, a measurable (or "minimal") level for residual disease (MRD) provides important prognostic information. Numerous studies have shown that achieving a negative MRD is a reliable predictor of better long-term outcomes in AML patients.
Interestingly, the recently revised European Leukemia Net recommendations for AML management have introduced the category CR without MRD.
AML is the most common indication for alloSCT. Improvements in disease risk stratification using genetic and MRD technologies allow for the correct identification of high-risk patients who require alloSCT The increased donor availability combined with modern conditioning regimens, has significantly increase access of alloSCT for high-risk AML patients.
Despite the accumulated experience over the last four decades, relapse continues to represent the
BECTHHK rEMATOfiOrUH, TOM XVII, № 3, 2021
commonest cause of transplant failure. Therefore, the development of strategies with the potential to reduce disease recurrence represents a serious need. A number of retrospective analyses showed that MRD level prior alloSCT is an important prognostic risk factor of relapse. Therapy before alloSCT can affect both the MRD status before transplantation and the relapse risk after allograft. Thus, treatment aimed at reducing the burden of MRD before alloSCT may improve transplant outcome.
Along with the achievement of CR with MRD negativity, genetic markers of AML have significant predictive effect on clinical outcome and usually guide treatment strategies. In over 90% of AML patients, different molecular aberrations may be identified by next-generation sequencing (NGS) This technology use into clinical practice for the initial mutational screening at the time of AML diagnosis. Moreover, the use of NGS for MRD detection is attractive because its flexibility allow almost every mutated gene to be used as a MRD marker.
However, it must be assumed that some mutations can occur in hematopoietic cells as a part of clonal
hematopoiesis (CH). CH is found in a population of cells derived from somatically mutated hematopoietic stem cells. This process often accompanies aging, and then it is called age-related CH (ARCH). On the other hand, CH can also be a precursor of hematological neoplasms. In that cases it is called CH with indeterminate potential (CHIP).
The presence of CHIP with a fraction of mutant alleles of at least 2% in individuals without any signs of of neoplasms is associated with an increase of hematopoietic malignancies up to a maximum of 1% per year. The most frequently mutated gene in CH is DNMT3A, which, as shown in previously studies, could not predict relapse of disease as a marker of MRD.
In conclusion, molecular genetic studies is widely applicable to AML patients, is highly predictive of relapse and survival, and can help clarify the indications for alloASCT and post-transplantation management in AML patients.
