CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2020; 41(06): 850-858
DOI: 10.4103/ijmpo.ijmpo_195_20
Original Article

Human leukocyte antigen associations with acute leukemia: An indian perspective

Hina Solanki
Chimera Transplant Research Foundation, Masjid Moth, South Extension, New Delhi; Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
Vikash C. Mishra
Chimera Transplant Research Foundation, Masjid Moth, South Extension, New Delhi; Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
Aseem K. Tiwari
Department of Transfusion Medicine, Medanta The Medicity, Gurgaon, Haryana, India
Nipun Kakkar
Department of Pediatric Oncology, Baylor College of Medicine, Houston, Texas, India
Naveen Vashisht
Chimera Transplant Research Foundation, Masjid Moth, South Extension, New Delhi, India
Vimarsh Raina
Chimera Transplant Research Foundation, Masjid Moth, South Extension, New Delhi, India
Girish Sharma
Centre for Medical Biotechnology, Amity Institute of Biotechnology; Amity Center for Cancer Epidemiology and Cancer Research, Amity University, Noida, Uttar Pradesh, India
› Author Affiliations
Financial support and sponsorship Nil.


Objective: Acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) are neoplastic blood disorders in which the cancerous white blood cells accumulate, resulting in a significant morbidity and mortality. Human leukocyte antigen (HLA) association is observed as one of the factors in the development of leukemia. The objective of the present study was to analyze the allele frequency of HLA Class I (HLA-A, HLA-B, and HLA-C) and Class II (HLA-DRB1 and HLA-DQB1) in Indian acute leukemia patients and to compare them with the frequencies in healthy, unrelated Indian individuals. Materials and Methods: We included 500 Indian leukemic patients (AML = 324 and ALL = 176) and 1000 unrelated, healthy, Indian individuals as controls. The HLA typing was performed using polymerase chain reaction with sequence-specific oligonucleotide probes. Results: On univariate analysis, allele frequencies of HLA-AFN*0111 and HLA-DRB1FN*0111 were lower in patients with ALL (P = 0.0181 and P = 0.0025, respectively). Whereas of HLA-AFN*0111, HLA-DRB1FN*0111, and HLA-BFN*0151, these frequencies were relatively lower in patients with acute leukemia (AML + ALL) (P = 0.0382, P = 0.0093 and P = 0.0384, respectively) and HLA-CFNx0101 (P = 0.0304) in AML when compared with control individuals. In contrast, the HLA-BFN*0139 and HLA-CFN*0107 allele frequency was higher in acute leukemia (P = 0.00372 and P = 0.0463, respectively) and in AML (P = 0.0010 and P = 0.0178, respectively) than that in controls. On multivariate analysis, BFNx0139 showed positive associations with acute leukemia (P = 0.006) and AML (P = 0.002). HLA-AFN*0111 and-DRB1FN*0111 showed a negative association with acute leukemia (P = 0.009 and P < 0.0001, respectively) and ALL (P = 0.013 and P < 0.0001, respectively). Conclusions: The HLA-BFN*0139 has a positive association with AML and acute leukemia, whereas HLA-AFN*0111 and HLA-DRB1FN*0111 alleles have negative association with ALL and HLA-BFN*0151 along with these two alleles with acute leukemia. No positive association was observed with ALL. HLA-CFN*0101 frequency was lower in AML patients than that in controls.

Publication History

Received: 26 April 2020

Accepted: 02 October 2020

Article published online:
14 May 2021

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  • References

  • 1 Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57-70
  • 2 Pui CH, Relling MV, Downing JR. Acute lymphoblastic leukemia. N Engl J Med 2004; 350: 1535-48
  • 3 Terasaki pI. editor History of HLA: Ten Recollections. Los Angeles: UCLA Tissue Typing Laboratory Press; 1990
  • 4 Corzo D, Salazar M, Granja CB, Yunis EJ. Advances in HLA genetics. Exp Clin Immunogenet 1995; 12: 156-70
  • 5 Baur MP, Danilovs J. Population Genetic Analysis of HLA-A, B, C, DR and other Genetic Markers. In: Terisaki PI. editors Histocompatibility Testing. Los Angeles (CA): UCLA Tissue Typing Laboratory; 1980. p. 955-93
  • 6 Ward FE, Amos DB. Human leukocyte antigens and disease. In: Litwin SD. editors Human Immunogenetics M-Q Basic Principles and Clinical Relevance. New York: Marcel Dekker, Inc; 1980. p. 359-78
  • 7 Lechler R, Warrens A. HLA in Health and Disease. London: Academic Press Limited; March 2000
  • 8 Lilly F, Boyse EA, Old LJ. Genetic basis of susceptibility to viral leukemogenesis. Lancet 1964; 2: 1207-9
  • 9 Dausset J. The major histocompatibility complex in man. Science 1981; 213: 1469-74
  • 10 Walford RL, Finkelstein S, Neerhout R, Konrad P, Shanbrom E. Acute childhood leukemia in relation to the HLA human transplantation genes. Nature 1970; 5231: 461-2
  • 11 Seremetis S, Cuttner J, Winchester R. Definition of a possible genetic basis for susceptibility to acute myelogenous leukemia associated with the presence of a polymorphic Ia epitope. J Clin Invest 1985; 76: 1391-7
  • 12 Bortin MM, D'Amaro J, Bach FH, Rimm AA, van Rood JJ. HLA associations with leukemia. Blood 1987; 70: 227-32
  • 13 Muller CA, Ilasmann R, Grosse WildeeFT. Significant association of acute lymphoblastic leukaemia with HLA-Cw7. Genet Epidemiol 1988; 5: 453-61
  • 14 Yoon J. Acute myeloid leukemia is a disease associated with HLA-C3. Acta Haematol 2015; 133: 164-7
  • 15 Available from: [Last accessed on 2020 Mar 30].
  • 16 Svejgaard A, Ryder LP. HLA and disease associations: Detecting the strongest association. Tissue Antigens 1994; 43: 18-27
  • 17 Fernandes TA, Fukai R, Souza CA, Lorand-Metze I, Magna LA, Kraemer MH. Molecular identification of the HLA-DRB1-DQB1 for diagnosis and follow-up of acute leukemias. Blood Cells Mol Dis 2010; 44: 69-73
  • 18 Villalobos C, Rivera S, Weir-Medina J, Hassanhi M, Montiel M, González R. Association of HLA class I and leukemia in mestizo patients of the state of Zulia, Venezuela. Invest Clin 2003; 44: 283-9
  • 19 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: 1835-44
  • 20 Layrisse Z, Guedez Y, Dominguez E, Herrera F, Soto M, Balbas O. et al. Extended HLA haplotypes among the Bari Amerindians of the Perija Range. Relationship to other tribes based on four-loci haplotype frequencies. Hum Immunol 1995; 44: 228-35
  • 21 Klitz W, Gragert L, Trachtenberg E. Spectrum of HLA associations: The case of medically refractory pediatric acute lymphoblastic leukemia. Immunogenetics 2012; 64: 409-19
  • 22 Fernández-Torres J, Flores-Jiménez D, Arroyo-Pérez A, Granados J, López-Reyes A. HLA-BFNx0140 allele plays a role in the development of acute leukemia in Mexican population: A case-control study. Biomed Res Int 2013; 2013: 705862
  • 23 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 2011; 25: 1036-9
  • 24 Rothhammer F, Silva C, allegari-Jacques SM, Llop E, Salzano FM. Gradients of HLA diversity in South American Indians. Ann Hum Biol 1997; 24: 197-208