Human leukocyte antigen-DRB 1 polymorphism in childhood acute lymphoblastic leukemia

Similar to autoimmune diseases, there are clear associations between resistance or susceptibility to cancer and the classic human leukocyte antigen (HLA) profile of an individual. HLA-associated susceptibility to childhood acute lymphoblastic leukemia (ALL) may provide clues to leukemogenesis in general and to the role of other risk factors. The present study aimed to determine the association between the HLA-DRB1 genotype and susceptibility to ALL in children and to assess the prognostic value of HLA‐DRB1 alleles in these patients. This study included 50 ALL patients who were consecutively admitted to the Pediatric Oncology Unit of Zagazig University Hospital and 50 gender-matched healthy volunteers as a control group. The patients were subjected to full clinical history, thorough clinical examination and routine laboratory investigations. Molecular HLA‐DRB1 typing for patients and controls using the reverse sequence-specific oligonucleotide probe technique was performed. HLA‐DRB1*04 allele frequency was significantly higher in female patients compared to that in female controls (P=0.03) and in patients aged <10 years compared to those aged ≥10 years at the time of diagnosis (P=0.01). HLA‐DRB1*11 allele frequency was significantly higher in high-risk compared to standard-risk patients (P=0.01) and in refractory patients compared to those who achieved remission (P=0.02). In conclusion, the HLA‐DRB1*04 allele appears to be a female-specific susceptibility factor for the acquisition of childhood ALL and it may affect the age of onset of ALL. In addition, the HLA‐DRB1*11 allele may be of prognostic significance in childhood ALL. However, further larger studies are required to support the conclusions drawn from this study. Introduction Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children, representing one quarter of all pediatric cancers worldwide (1). Over 40 years since the first associations between particular human leukocyte antigen (HLA) profiles and disease susceptibility were described, the identification of large numbers of HLA-associated diseases parallels our improved understanding of the genetic complexity of the HLA system and its extensive polymorphism. These associations involve malignant as well as autoimmune diseases, including the well-known association between HLA-B27 and ankylosing spondylitis. Over time, several hundred diseases have been reported to occur more frequently in individuals with particular HLA genotypes (2). These diseases include a broad spectrum of immune‐mediated diseases involving all major organ systems, certain malignancies, infectious diseases and, more recently, adverse reactions to particular drugs (2). One of the factors that may determine whether a child develops ALL is how it responds to the candidate infection. Since immune responses to infection are under the partial control of HLA genes, an association between an HLA allele and ALL may provide support for an infectious etiology (3). The biological significance of the association between HLA types and acute leukemia is emphasized by the fact that HLA may be involved in disease susceptibility or resistance. It is important to investigate the HLA-associated susceptibility to childhood ALL, as this may provide clues to leukemogenesis in general and to the role of other risk factors (4). The present study aimed to determine the association between the HLA-DRB1 genotype and the susceptibility to ALL in children and to evaluate the prognostic value of HLA-DRB1 alleles in these patients. Patients and methods Patients. This study was performed on 50 ALL patients who were consecutively admitted to the Pediatric Oncology Unit of Zagazig University Hospital and 50 gender-matched healthy volunteers as a control group. The patients were subjected to: i) full clinical history and thorough clinical examination; and ii) routine laboratory Human leukocyte antigen-DRB1 polymorphism in childhood acute lymphoblastic leukemia MERVAT M. EL ANSARY1, LAMIAA A. MOHAMMED2, TAMER H. HASSAN3, AHMED BARAKA2 and ALSHYMAA A. AHMED2 1Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo 11562; Departments of 2Clinical Pathology and 3Pediatrics, Faculty of Medicine, Zagazig University, Zagazig 44111, Egypt Received October 9, 2014; Accepted November 6, 2014 DOI: 10.3892/mco.2014. 466 Correspondence to: Dr Tamer H. Hassan, Department of Pediatrics, Zagazig University, Zagazig University Street, Zagazig 44111, Egypt E-mail: dr.tamerhassan@yahoo.com