Contributions
Abstract: S1584
Type: Oral Presentation
Presentation during EHA23: On Sunday, June 17, 2018 from 09:00 - 09:15
Location: Room A8
Background
Chronic Idiopathic Neutropenia (CIN) is a mild bone marrow (BM) failure syndrome characterized by presence of myelosuppressive oligoclonal/monoclonal T-cell populations and usually benign course. The possible association of CIN with the Single Nucleotide Polymorphism (SNP) GATA -67T>C (rs2814778) of the Duffy Antigen Receptor for Chemokines (DARC), also known as Atypical Chemokine Receptor 1 (ACKR1) gene, associated with the benign Ethnic Neutropenia, has never been studied so far. This polymorphism is associated with the red blood cell Duffy Null phenotype; it is rare among individuals of European descent but common in Africans, African Americans and Yemenite Jews, populations characterized by the benign Ethnic Neutropenia. The mechanism of neutropenia implicates the Duffy-mediated regulation of chemokine gradients resulting in neutrophil influx from blood into the tissues.
Aims
The aim of the study was to evaluate the genotype and allele frequency of the rs2814778 SNP in patients with CIN living in the island of Crete, Greece.
Methods
We studied 50 patients (45 females, 5 males) fulfilling the previously defined diagnostic criteria of CIN. Specifically, the patients had absolute neutrophil counts (ANC) below 1800 x 106/L (mean 1206 ± 477) at least for 3 months, no evidence of any underlying disease associated with neutropenia, no history of exposure to irradiation, use of chemical compounds or intake of drugs to which neutropenia might be ascribed, normal BM karyotype and negative antineutrophil antibodies. Two patients were of Balkan and one of English origin whereas the others originated from Crete. DNA was extracted from peripheral blood samples (Qiagen) and the genotyping for the rs2814778 SNP of the DARC gene was performed using the TaqMan SNP Genotyping Assay C__15769614_10 (Thermo Fisher Scientific).
Results
Four patients (one of Balkan and three of Cretan origin), representing a percentage of 8% of the CIN patients examined, were found to be homozygous for the C allele of rs2814778 (also designated as FY*BES/FY*BES); five patients (all of Cretan origin) i.e. a percentage of 10% were heterozygous (T/C or FY*B/FY*BES) for the DARC SNP under study. Red blood cell phenotyping was performed in one of the homozygous patients and was Duffy Null, as anticipated. No statistically significant differences were found between T/T CIN patients and the carriers of C allele (C/C or T/C) regarding gender, ANC, haemoglobin, lymphocytes and platelet counts. We also investigated the above groups for potential differences in parameters previously reported to characterize CIN. Specifically, we evaluated the serum immunoglobulin levels and the frequency of oligoclonal/monoclonal T-cell populations using flow-cytometric analysis but no significant differences were identified.
Conclusion
This is the first study demonstrating that the C/C (FY*BES/FY*BES) homozygosity of the rs2814778 SNP, implicated in Ethnic Neutropenia, is not rare among European patients with CIN. Therefore, the genotyping for rs2814778 SNP of DARC gene should be incorporated in the initial investigation of any patient with chronic unexplained neutropenia. We are currently investigating the correlation between the rs2814778 genotype and the red blood cell phenotype to simplify this initial screening and we are also organizing a large case-control study in Cretan population aiming to identify the genotype and allelic frequencies of the rs2814778 SNP and its potential association with the diagnosis of CIN.
Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Keyword(s): neutropenia, Single nucleotide polymorphism
Abstract: S1584
Type: Oral Presentation
Presentation during EHA23: On Sunday, June 17, 2018 from 09:00 - 09:15
Location: Room A8
Background
Chronic Idiopathic Neutropenia (CIN) is a mild bone marrow (BM) failure syndrome characterized by presence of myelosuppressive oligoclonal/monoclonal T-cell populations and usually benign course. The possible association of CIN with the Single Nucleotide Polymorphism (SNP) GATA -67T>C (rs2814778) of the Duffy Antigen Receptor for Chemokines (DARC), also known as Atypical Chemokine Receptor 1 (ACKR1) gene, associated with the benign Ethnic Neutropenia, has never been studied so far. This polymorphism is associated with the red blood cell Duffy Null phenotype; it is rare among individuals of European descent but common in Africans, African Americans and Yemenite Jews, populations characterized by the benign Ethnic Neutropenia. The mechanism of neutropenia implicates the Duffy-mediated regulation of chemokine gradients resulting in neutrophil influx from blood into the tissues.
Aims
The aim of the study was to evaluate the genotype and allele frequency of the rs2814778 SNP in patients with CIN living in the island of Crete, Greece.
Methods
We studied 50 patients (45 females, 5 males) fulfilling the previously defined diagnostic criteria of CIN. Specifically, the patients had absolute neutrophil counts (ANC) below 1800 x 106/L (mean 1206 ± 477) at least for 3 months, no evidence of any underlying disease associated with neutropenia, no history of exposure to irradiation, use of chemical compounds or intake of drugs to which neutropenia might be ascribed, normal BM karyotype and negative antineutrophil antibodies. Two patients were of Balkan and one of English origin whereas the others originated from Crete. DNA was extracted from peripheral blood samples (Qiagen) and the genotyping for the rs2814778 SNP of the DARC gene was performed using the TaqMan SNP Genotyping Assay C__15769614_10 (Thermo Fisher Scientific).
Results
Four patients (one of Balkan and three of Cretan origin), representing a percentage of 8% of the CIN patients examined, were found to be homozygous for the C allele of rs2814778 (also designated as FY*BES/FY*BES); five patients (all of Cretan origin) i.e. a percentage of 10% were heterozygous (T/C or FY*B/FY*BES) for the DARC SNP under study. Red blood cell phenotyping was performed in one of the homozygous patients and was Duffy Null, as anticipated. No statistically significant differences were found between T/T CIN patients and the carriers of C allele (C/C or T/C) regarding gender, ANC, haemoglobin, lymphocytes and platelet counts. We also investigated the above groups for potential differences in parameters previously reported to characterize CIN. Specifically, we evaluated the serum immunoglobulin levels and the frequency of oligoclonal/monoclonal T-cell populations using flow-cytometric analysis but no significant differences were identified.
Conclusion
This is the first study demonstrating that the C/C (FY*BES/FY*BES) homozygosity of the rs2814778 SNP, implicated in Ethnic Neutropenia, is not rare among European patients with CIN. Therefore, the genotyping for rs2814778 SNP of DARC gene should be incorporated in the initial investigation of any patient with chronic unexplained neutropenia. We are currently investigating the correlation between the rs2814778 genotype and the red blood cell phenotype to simplify this initial screening and we are also organizing a large case-control study in Cretan population aiming to identify the genotype and allelic frequencies of the rs2814778 SNP and its potential association with the diagnosis of CIN.
Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Keyword(s): neutropenia, Single nucleotide polymorphism