Frequencies of HLA Alleles in Patients with Acute Lymphoblastic and Myeloid Leukemia

Main Article Content

Rasime Derya Güleç
Fatma Demet Arslan

Abstract

Objective: Our objective was to investigate the potential correlation between human leukocyte antigens (HLA) - specifically, HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 genes - and patients diagnosed with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).


Material and Methods: We conducted an analysis of HLA allele frequencies among 393 patients with ALL, 431 patients with AML, and a control group comprising 564 healthy donors. Additionally, we explored the variation in HLA allele distribution between pediatric and adult patients diagnosed with ALL.


Results: In comparison to the donor group, a heightened frequency of HLA-A*32 antigen was observed in AML patients (p=0.015, OR: 1.682). Conversely, the frequencies of HLA-B*55 (p=0.027, OR: 0.545) in ALL patients, HLA-B*14 (p=0.023, OR: 0.397), and HLA-B*55 (p=0.04, OR: 0.604) in AML patients were notably diminished. Notably, there were no discernible differences in HLA Class II allele frequency and analysis between the patient and control groups. Moreover, a significant distinction in the frequencies of HLA-A*25 (p=0.019, OR: 8.426) and DRB1*04 (p=0.049, OR: 1.491) was identified between pediatric patients (n=165) and adult patients (n=228) with ALL.


Conclusion: The findings indicate that HLA-A*32 might serve as a genetic predisposing factor for AML, and HLA-A*25 and DRB1*04 could be potential genetic risk factors for pediatric ALL patients. Conversely, HLA-B*55 appears to be a potential protective factor against both forms of acute leukemia.

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How to Cite
Güleç, R. D., & Arslan, F. D. (2023). Frequencies of HLA Alleles in Patients with Acute Lymphoblastic and Myeloid Leukemia. Medical Science and Discovery, 10(8), 539–545. https://doi.org/10.36472/msd.v10i8.994
Section
Research Article
Received 2023-07-17
Accepted 2023-08-16
Published 2023-08-17

References

Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–2405.

Gilliland DG, Tallman MS. Focus on acute leukemias. Cancer cell. 2002; 1(5), 417-420.

Kennedy AE, Ozbek U, Dorak MT. What has GWAS done for HLA and disease associations? Int J Immunogenet. 2017;44(5):195–211.

Salvadori L de C, Santana FC de S, Marcos EVC. Frequency of alleles and haplotypes of the human leukocyte antigen system in Bauru, São Paulo, Brazil. Rev Bras Hematol Hemoter. 2014;36(2):108–14.

Fernandes TAR, Fukai R, Souza CA, Lorand-Metze I, Magna LA, Kraemer MHS. Molecular identification of the HLA-DRB1-DQB1 for diagnosis and follow-up of acute leukemias. Blood Cells, Mol Dis. 2010;44(2):69–73.

Gao S, Cheng L, Lu L, Jing S, Cheng X, Zhang Y, et al. Analysis of HLA haplotype frequency and linkage disequilibrium in patients with acute lymphoblastic leukemia from Northern Chinese Han. Zhonghua yi xue yi Chuan xue za zhi= Zhonghua Yixue Yichuanxue Zazhi= Chinese J Med Genet. 2009;26(1):82–6.

Hojjat-Farsangi M, Jeddi-Tehrani M, Amirzargar AA, Razavi SM, Sharifian RA, Rabbani H, et al. Human leukocyte antigen class II allele association to disease progression in Iranian patients with chronic lymphocytic leukemia. Hum Immunol. 2008;69(10):666–74.

Malcolm Taylor G. Genetic susceptibility to childhood common acute lymphoblastic leukaemia is associated with polymorphic peptide-binding pocket profiles in HLA-DPB1*0201. Hum Mol Genet. 2002;11(14):1585–97. https://doi.org/10.1093/hmg/11.14.1585

Dorak MT, Oguz FS, Yalman N, Diler AS, Kalayoglu S, Anak S, et al. A male-specific increase in the HLA-DRB4 (DR53) frequency in high-risk and relapsed childhood ALL. Leuk Res. 2002;26(7):651–6.

Dorak MT, Lawson T, Machulla HKG, Darke C, Mills KI, Burnett AK. Unravelling an HLA-DR Association in Childhood Acute Lymphoblastic Leukemia. Blood. 1999;94(2):694–700.

Yari F, Sobhani M, Sabaghi F, Zaman-Vaziri M, Bagheri N, Talebian A. Frequencies of HLA-DRB1 in Iranian Normal Population and in Patients with Acute Lymphoblastic Leukemia. Arch Med Res. 2008;39(2):205–8.

Patiroglu T, Akar HH. Relationships of human leukocyte antigen-A,-B,-DRB1 alleles, and haplotypes in 129 ethnic Turkish patients with acute myeloblastic leukemia. Lab Med. 2015;46(3):195–9.

Klitz W, Gragert L, Trachtenberg E. Spectrum of HLA associations: the case of medically refractory pediatric acute lymphoblastic leukemia. Immunogenetics. 2012;64:409–19.

Kazemi MH, Momeni-Varposhti Z, Roshandel E, Sankanian G, Rouzbahani NH, Ghorban K, et al. Association of HLA alleles with hematologic malignancies. Gene Reports. 2021;25:101346.

Kabbaj M, Oudghiri M, Naya A, Naamane H, El Turk J, Bennani S, et al. HLA-A, -B, -DRB1 alleles and haplotypes frequencies in Moroccan patients with leukemia. Ann Biol Clin. 2010;68(3):291–6.

Arnaiz‐Villena A, Karin M, Bendikuze N, Gomez‐Casado E, Moscoso J, Silvera C, et al. HLA alleles and haplotypes in the Turkish population: relatedness to Kurds, Armenians and other Mediterraneans. Tissue Antigens. 2001;57(4):308–317.

MHC Sequencing Consortium. Complete sequence and gene map of a human major histocompatibility complex. Nature. 1999;401(6756):921–3.

Allcock RJN, Atrazhev AM, Beck S, De Jong PJ, Elliott JF, Forbes S, et al. The MHC haplotype project: A resource for HLA-linked association studies. Tissue Antigens. 2002;59(6):520–1.

Horton R, Wilming L, Rand V, Lovering RC, Bruford EA, Khodiyar VK, et al. Gene map of the extended human MHC. Nat Rev Genet. 2004;5(12):889–99.

Lenz TL, Spirin V, Jordan DM, Sunyaev SR. Excess of Deleterious Mutations around HLA Genes Reveals Evolutionary Cost of Balancing Selection. Mol Biol Evol. 2016;33(10):2555–64.

Urayama KY, Chokkalingam AP, Manabe A, Mizutani S. Current evidence for an inherited genetic basis of childhood acute lymphoblastic leukemia. Int J Hematol. 2013;97(1):3–19.

Sayad A, Akbari MT, Ostadali M, Hamidieh AA, Arsang-Jang S, Hajifathali A, et al. Comprehensive assessment of association between HLA polymorphisms and acute leukemia in Iranian population. Gene Reports. 2020;19(6):100674.

Hosking FJ, Leslie S, Dilthey A, Moutsianas L, Wang Y, Dobbins SE, et al. MHC variation and risk of childhood B-cell precursor acute lymphoblastic leukemia. Blood. 2011;117(5):1633–40.

Müller C, Hasmann R, Grosse-Wilde H, Vögeler U, Bei-Jun C, Dopfer R, et al. Significant association of acute lymphoblastic leukemia with HLA-Cw7. Genet Epidemiol. 1988;5(6):453–61.

Bortin M, D’Amaro J, Bach F, Rimm A, van Rood J. HLA associations with leukemia. Blood. 1987;70(1):227–32.

Yoon J. Acute myeloid leukemia is a disease associated with HLA-C3. Acta Haematol. 2015;133(2):164–7.

Solanki H, Tiwari AK, Raina V, Sharma G. Association study of HLA class I and class II alleles with childhood acute lymphoblastic leukemia in Indian patients. Gene Reports. 2021;23:101086.

Albert ED, Nisperos B, Thomas ED. HLA antigens and haplotypes in acute leukemia. Leuk Res. 1977;1(4):261–9.

Gai E, Gruia A, Boldeanu F, Serban M, Arghirescu S, Jinca C, et al. Relationship between HLA A*02 A*03 association and the risk of childhood acute leukeia. J Exp Mol Biol. 2010;11(2–3):1985–8.

Ozdilli K, Oguz FS, Anak S, Kekik C, Carin M, Gedikoglu G. The frequency of HLA class I and II alleles in turkish childhood acute leukaemia patients. J Int Med Res. 2010;38(5):1835–44.

Uçar F, Sönmez M, Erkut N, Balci M, Yücel B, Yilmaz M, et al. Relation of HLA-A, -B, -DRB1 Alleles and Haplotypes in Patients with Acute Leukemia: A Case Control Study. Arch Med Res. 2011;42(4):305–10.

Patıroğlu T, Akar HH. The Frequency of HLA-A, HLA-B, and HLA-DRB1 Alleles in Patients with Acute Lymphoblastic Leukemia in the Turkish Population: A Case-Control Study. Turkish J Hematol. 2016;33(4):339–45.

Oguz SR, Senturk Ciftci H, Gokce M, Ogret Y, Kivanc D, Ozdilli K, et al. HLA DRB1 alleles, IFN- γ and TGF- β Gene Variants in childhood ALL patients. Turkish J Biochem. 2022.

Orouji E, Tavakkol Afshari J, Badiee Z, Shirdel A, Alipour A. Association between HLA-DQB1 gene and patients with acute lymphoblastic leukemia (ALL). Int J Hematol. 2012;95(5):551–5.

Vonfliedner VE, Sultan Khan Z, Jeannet M. HLA-A and HLA-B antigens in acute leukemia: A2-B12 phenotypes correlate with longer survival in acute myelogenous leukemia. Acta Haematol. 1981;65(2):73–8.

Urayama KY, Chokkalingam AP, Metayer C, Ma X, Selvin S, Barcellos LF, et al. HLA-DP genetic variation, proxies for early life immune modulation and childhood acute lymphoblastic leukemia risk. Blood. 2012;120(15):3039–47.

Fernández-Torres J, Flores-Jiménez D, Arroyo-Pérez A, Granados J, López-Reyes A. HLA-B40 allele plays a role in the development of acute leukemia in mexican population: A case-control study. Biomed Res Int. 2013;2013:7–10.

Davey FR, Lachant NA, Dock NL, Hubbell C, Stockman III JA, Henry JB. HLA Antigens and Childhood Acute Lymphocytic Leukaemia. Br J Haematol. 1981;47(2):211–20.

Dearden SP, Taylor GM, Gokhale DA, Robinson MD, Thompson W, Ollier W, et al. Molecular analysis of HLA-DQB1 alleles in childhood common acute lymphoblastic leukemia. Br. J. Cancer 1996;73(5):603-609.

Taylor GM, Hussain A, Verhage V, Thompson PD, Fergusson WD, Watkins G, et al. Strong association of the HLA-DP6 supertype with childhood leukaemia is due to a single allele, DPB1*0601. Leukemia. 2009;23(5):863–9.