Volume 16, Issue 2 (June 2024 2024)                   Iranian Journal of Blood and Cancer 2024, 16(2): 24-33 | Back to browse issues page


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Hassan N, Idris S Z, Chang K M, Osman R, Mohd Ibrahim H, Dhaliwal J S et al . High Variability in HLA-DRB1*03, a Predisposing Allele in Acute Lymphoblastic Leukemia. Iranian Journal of Blood and Cancer 2024; 16 (2) :24-33
URL: http://ijbc.ir/article-1-1534-en.html
1- UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia
2- Department of Pathology, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
3- Department of Hematology, Hospital Ampang, Clinical Hematology Laboratory, Jalan Mewah Utara, Pandan Mewah, Ampang, Selangor 68000, Malaysia
4- Hematology Unit, Hospital Kuala Lumpur, Jalan Pahang, 50586 Wilayah, Persekutuan Kuala Lumpur, Malaysia
5- Pediatric Department, Hospital Kuala Lumpur, 50586 Wilayah, Persekutuan Kuala Lumpur, Malaysia
6- Allergy and Immunology Research Centre, Institute for Medical Research, 50588 Jalan Pahang, Kuala Lumpur
7- Department of Pathology, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia , maha@upm.edu.my
Abstract:   (888 Views)
Acute lymphoblastic leukemia (ALL) remains a significant health concern, particularly in children, with genetic predisposition playing a crucial role in its etiology. Among the predisposing HLA Class II alleles, —DRB1*03 has emerged as a notable candidate associated with increased susceptibility to ALL. This study aims to investigate the extent of variability within the HLA-DRB1 alleles as genetic biomarkers and its implications in ALL pathogenesis. Through methods of polymerase chain reaction—sequence-specific oligonucleotides (PCR-SSO) and sequence-based typing (SBT) analysis, our data revealed HLA-DRB1*16 as another genetic risk and HLA-DRB1*07 and HLA-DRB1*12 alleles as protective alleles in ALL patients. Further sequencing demonstrates a remarkable diversity in the HLA-DRB1*03 allele in ALL patients but none among the HLA-DRB1*16 alleles compared to normal samples. Our findings confirmed the association of HLA-DRB1 alleles with ALL and shed light on SNPs or mutations in the risk alleles. Genetic variability in HLA-DRB1 alleles is a significant factor to consider in improving outcomes in immunotherapy.
Full-Text [PDF 1259 kb]   (444 Downloads)    
: Original Article | Subject: Pediatric Hematology & Oncology
Received: 2024/03/29 | Accepted: 2024/05/24 | Published: 2024/06/30

References
1. Karp DR, Teletski CL, Scholl P, Geha R, Long EO. The α1 domain of the HLA-DR molecule is essential for high-affinity binding of the toxic shock syndrome toxin-1. Nature 1990 346:6283 [Internet]. 1990 [cited 2023 Sep 13];346(6283):474-6. Available from: https://www.nature.com/articles/346474a0 [DOI:10.1038/346474a0]
2. Reche PA, Reinherz EL. Sequence variability analysis of human class I and class II MHC molecules: Functional and structural correlates of amino acid polymorphisms. J Mol Biol [Internet]. 2003 Aug 15 [cited 2023 Sep 13];331(3):623-41. Available from: https://pubmed.ncbi.nlm.nih.gov/12899833/ [DOI:10.1016/S0022-2836(03)00750-2]
3. Campbell RD, Trowsdale J. Map of the human MHC. Immunol Today [Internet]. 1993 [cited 2023 Sep 13];14(7):349-52. Available from: https://pubmed.ncbi.nlm.nih.gov/8363724/ [DOI:10.1016/0167-5699(93)90234-C]
4. Beck S, Geraghty D, Inoko H, Rowen L, Aguado B, Bahram S, et al. Complete sequence and gene map of a human major histocompatibility complex. Nature 1999 401:6756 [Internet]. 1999 Oct 28 [cited 2024 Mar 13];401(6756):921-3. Available from: https://www.nature.com/articles/44853 [DOI:10.1038/44853]
5. Ejsmond MJ, Radwan J. Red Queen Processes Drive Positive Selection on Major Histocompatibility Complex (MHC) Genes. PLoS Comput Biol [Internet]. 2015 Nov 1 [cited 2024 Mar 13];11(11). Available from: /pmc/articles/PMC4658181/ [DOI:10.1371/journal.pcbi.1004627]
6. Barker DJ, Maccari G, Georgiou X, Cooper MA, Flicek P, Robinson J, et al. The IPD-IMGT/HLA Database. Nucleic Acids Res [Internet]. 2023 Jan 6 [cited 2023 Sep 13];51(D1):D1053-60. Available from: https://pubmed.ncbi.nlm.nih.gov/36350643/ [DOI:10.1093/nar/gkac1011]
7. Ritari J, Koskela S, Hyvärinen K, FinnGen, Partanen J. HLA-disease association and pleiotropy landscape in over 235,000 Finns. Hum Immunol [Internet]. 2022 May 1 [cited 2023 Sep 13];83(5):391-8. Available from: https://pubmed.ncbi.nlm.nih.gov/35221124/ [DOI:10.1016/j.humimm.2022.02.003]
8. Blackwell JM, Jamieson SE, Burgner D. HLA and infectious diseases. Clin Microbiol Rev [Internet]. 2009 Apr [cited 2023 Sep 13];22(2):370-85. Available from: https://pubmed.ncbi.nlm.nih.gov/19366919/ [DOI:10.1128/CMR.00048-08]
9. Miyadera H, Tokunaga K. Associations of human leukocyte antigens with autoimmune diseases: challenges in identifying the mechanism. J Hum Genet [Internet]. 2015 Nov 1 [cited 2023 Sep 13];60(11):697-702. Available from: https://pubmed.ncbi.nlm.nih.gov/26290149/ [DOI:10.1038/jhg.2015.100]
10. Mogensen TH. Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses. Clin Microbiol Rev [Internet]. 2009 Apr [cited 2024 Mar 13];22(2):240. Available from: /pmc/articles/PMC2668232/ [DOI:10.1128/CMR.00046-08]
11. Wang QL, Wang TM, Deng CM, Zhang WL, He YQ, Xue WQ, et al. Association of HLA diversity with the risk of 25 cancers in the UK Biobank. EBioMedicine [Internet]. 2023 Jun 1 [cited 2024 Mar 13];92. Available from: http://www.thelancet.com/article/S2352396423001536/fulltext [DOI:10.1016/j.ebiom.2023.104588]
12. Beatty GL, Gladney WL. Immune escape mechanisms as a guide for cancer immunotherapy. Clin Cancer Res [Internet]. 2015 Feb 2 [cited 2024 Mar 13];21(4):687. Available from: /pmc/articles/PMC4334715/ [DOI:10.1158/1078-0432.CCR-14-1860]
13. Aktar N, Yueting C, Abbas M, Zafar H, Paiva-Santos AC, Zhang Q, et al. Understanding of Immune Escape Mechanisms and Advances in Cancer Immunotherapy. J Oncol. 2022;2022. [DOI:10.1155/2022/8901326]
14. James LM, Georgopoulos AP. Immunogenetics of posttraumatic stress disorder (PTSD) in women veterans. Brain Behav Immun Health [Internet]. 2022 Dec 1 [cited 2024 Mar 13];26. Available from: /pmc/articles/PMC9723517/ [DOI:10.1016/j.bbih.2022.100567]
15. Ruiz-Cabello F, Garrido F. HLA and cancer: from research to clinical impact. Immunol Today [Internet]. 1998 Dec 1 [cited 2024 Mar 13];19(12):539-42. Available from: https://pubmed.ncbi.nlm.nih.gov/9864942/ [DOI:10.1016/S0167-5699(98)01349-8]
16. Hicklin DJ, Marincola FM, Ferrone S. HLA class I antigen downregulation in human cancers: T-cell immunotherapy revives an old story. Mol Med Today [Internet]. 1999 Apr 1 [cited 2024 Mar 13];5(4):178-86. Available from: https://pubmed.ncbi.nlm.nih.gov/10203751/ [DOI:10.1016/S1357-4310(99)01451-3]
17. Bukur J, Jasinski S, Seliger B. The role of classical and non-classical HLA class I antigens in human tumors. Semin Cancer Biol. 2012;22:350-8. [DOI:10.1016/j.semcancer.2012.03.003]
18. Shukla SA, Rooney MS, Rajasagi M, Tiao G, Dixon PM, Lawrence MS, et al. Comprehensive analysis of cancer-associated somatic mutations in class I HLA genes. Nature Biotechnology 2015 33:11 [Internet]. 2015 Sep 15 [cited 2024 Mar 13];33(11):1152-8. Available from: https://www.nature.com/articles/nbt.3344 [DOI:10.1038/nbt.3344]
19. Jan M, Leventhal MJ, Morgan EA, Wengrod JC, Nag A, Drinan SD, et al. Recurrent genetic HLA loss in AML relapsed after matched unrelated allogeneic hematopoietic cell transplantation. Blood Adv [Internet]. 2019 Jul 23 [cited 2024 Mar 13];3(14):2199-204. Available from: https://pubmed.ncbi.nlm.nih.gov/31324640/ [DOI:10.1182/bloodadvances.2019000445]
20. Mishra VC, Raina V, Sharma G. HLA association with leukemia: A review of the literature. Gene Rep. 2020 Dec 1;21:100939. [DOI:10.1016/j.genrep.2020.100939]
21. Dorak MT, Lawson T, Machulla HKG, Darke C, Mills KI, Burnett AK. Unravelling an HLA-DR Association in Childhood Acute Lymphoblastic Leukemia. Blood. 1999 Jul 15;94(2):694-700. [DOI:10.1182/blood.V94.2.694.414k07_694_700]
22. 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. [DOI:10.1016/S0145-2126(01)00189-8]
23. Malcolm Taylor G, Dearden S, Ravetto P, Ayres M, Watson P, Hussain A, et al. Genetic susceptibility to childhood common acute lymphoblastic leukaemia is associated with polymorphic peptide-binding pocket profiles in HLA-DPB1 * 0201. Hum Mol Genet [Internet]. 2002 Jul 1 [cited 2024 Mar 13];11(14):1585-97. Available from: https://dx.doi.org/10.1093/hmg/11.14.1585 [DOI:10.1093/hmg/11.14.1585]
24. Orouji E, Afshari JT, Badiee Z, Shirdel A, Alipour A. Association between HLA-DQB1 gene and patients with acute lymphoblastic leukemia (ALL). Int J Hematol [Internet]. 2012 May [cited 2024 Mar 13];95(5):551-5. Available from: https://pubmed.ncbi.nlm.nih.gov/22434102/ [DOI:10.1007/s12185-012-1051-8]
25. Yari F, Sobhani M, Sabaghi F, Zaman-Vaziri M, Bagheri N, Talebian A. Frequencies of HLA-DRB1 in Iranian normal population and patients with acute lymphoblastic leukemia. Arch Med Res [Internet]. 2008 Feb [cited 2024 Mar 13];39(2):205-8. Available from: https://pubmed.ncbi.nlm.nih.gov/18164964/ [DOI:10.1016/j.arcmed.2007.09.009]
26. 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 Feb 15;44(2):69-73. [DOI:10.1016/j.bcmd.2009.10.006]
27. de Carvalho DL, Barbosa CD, de Carvalho AL, Beck ST. Association of HLA antigens and BCR-ABL transcripts in leukemia patients with the Philadelphia chromosome. Rev Bras Hematol Hemoter [Internet]. 2012 [cited 2024 Mar 13];34(4):280. Available from: /pmc/articles/PMC3460407/ [DOI:10.5581/1516-8484.20120072]
28. Zhou M, Qiu H, Chen T, Xiao R, Yang J, Cen L, et al. Human leukocyte antigen (HLA)-DRB1*14 is associated with a high incidence of acute lymphocytic leukemia. Onkologie [Internet]. 2012 May [cited 2024 Mar 13];35(5):268-71. Available from: https://pubmed.ncbi.nlm.nih.gov/22868506/ [DOI:10.1159/000338480]
29. Dhaliwal JS, Shahnaz M, Too CL, Azrena A, Maiselamah L, Lee YY, et al. HLA-A,-B and-DR Allele and Haplo-type Frequencies in Malays. Asian Pac J Allergy Immunol. 2007;25:47-51.
30. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res [Internet]. 1988 Feb 11 [cited 2024 Mar 13];16(3):1215. Available from: https://pubmed.ncbi.nlm.nih.gov/3344216/ [DOI:10.1093/nar/16.3.1215]
31. Kotsch K, Wehling J, Blasczyk R, Blasczyk R. Sequencing of HLA class II genes based on the conserved diversity of the non-coding regions: sequencing based typing of HLA-DRB genes. Tissue Antigens [Internet]. 1999 [cited 2024 Mar 13];53:486-97. Available from: https://onlinelibrary.wiley.com/doi/10.1034/j.1399-0039.1999.530505.x [DOI:10.1034/j.1399-0039.1999.530505.x]
32. Naranbhai V, Viard M, Dean M, Groha S, Braun DA, Labaki C, et al. HLA-A*03 and response to immune checkpoint blockade in cancer: an epidemiological biomarker study. Lancet Oncol [Internet]. 2022 Jan 1 [cited 2024 Mar 18];23(1):172-84. Available from: https://mdanderson.elsevierpure.com/en/publications/hla-a03-and-response-to-immune-checkpoint-blockade-in-cancer-an-e [DOI:10.1016/S1470-2045(21)00582-9]
33. Klitz W, Gragert L, Trachtenberg E. Spectrum of HLA associations: the case of medically refractory pediatric acute lymphoblastic leukemia. Immunogenetics [Internet]. 2012 Jun [cited 2024 Mar 18];64(6):409. Available from: /pmc/articles/PMC3349849/ [DOI:10.1007/s00251-012-0605-5]
34. Park H, Hyun J, Park SS, Park MH, Song EY. False Homozygosity Results in HLA Genotyping due to Loss of Chromosome 6 in a Patient with Acute Lymphoblastic Leukemia. Korean J Lab Med [Internet]. 2011 Oct 31 [cited 2024 Mar 19];31(4):302. Available from: /pmc/articles/PMC3190013/ [DOI:10.3343/kjlm.2011.31.4.302]
35. Shah N, Decker WK, Lapushin R, Xing D, Robinson SN, Yang H, et al. HLA homozygosity and haplotype bias among patients with chronic lymphocytic leukemia: implications for disease control by physiological immune surveillance. Leukemia [Internet]. 2011 Jun [cited 2024 Mar 19];25(6):1036-9. Available from: https://pubmed.ncbi.nlm.nih.gov/21350559/ [DOI:10.1038/leu.2011.30]
36. Mumphrey MB, Hosseini N, Parolia A, Geng J, Zou W, Raghavan M, et al. Distinct mutational processes shape selection of MHC class I and class II mutations across primary and metastatic tumors. Cell Rep [Internet]. 2023 Aug 29 [cited 2024 Mar 28];42(8). Available from: https://pubmed.ncbi.nlm.nih.gov/37597185/ [DOI:10.1016/j.celrep.2023.112965]

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