Human leukocyte antigen-DRB1 polymorphism in childhood acute lymphoblastic leukemia

Abstract

Abstract. 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. IntroductionAcute 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 associati...

Do Gamma Rays of Cancer Radiotherapy Effect on the Sequence of Collagenase Gene?

“…Our findings are inconsistent with Elansary et al (2015), who reported that high significant increase allelic distribution in HLA-DRB1*11 and moderate decrease in HLADRB1*07 in AML patients in relative to controls which show no significant difference in our study (19). Bosen et al (2013), observed that the frequencies of the HLADRB1*15 alleles in patients with AML were significantly higher in AML patients compared with healthy controls, Du et a ( 2013 ), observed significant increase in allelic distribution of HLA-DRB1*07 in AML patients and suggests that it is susceptible to the disease in contrast to Ehernberg al (2014) observations.…”

“…These results not consistent with Chaing et al (2012) that demonstrated that allelic distribution of the HLA-DRB1*13 is significantly high among AML and overall acute leukemia patients group in relation to controls (7, 10, 17 and18). Few studies had been performed on HLA-G expression in different types of leukemia patients, however, data are limited and conclusions remain controversial and discordant (19).Regarding anti-HLA-G antibodies analysis, no significant association was found between patients and control groups. Also our results are inconsistent with the results of other authors who have not found membrane bound or cytoplasmic HLA-G expression (7).A group of previous studies addressed that no cell surface HLA-G was expressed in various types of hematopoietic diseases, such as AML, ALL, CLL and CML.…”

Human Leukocyte Antigen Alleles (HLA-A, HLA-B, and HLA-DRB1) are associated with Acute Lymphoblastic Leukemia (ALL) : A Case-Control Study in a Sample of Iranian Population

“…Investigations conducted in Eastern China have shown the significant role of the HLA-DRB114 locus in ALL, although no significant disparities were observed in the HLA-A and HLA-B loci between affected individuals and control groups [7]. Further studies have identified the HLA-DRB104 allele as increasing susceptibility to childhood ALL among females, additionally affecting the age at which the disease manifests [1].…”

“…

Acute lymphoblastic leukemia (ALL), the most prevalent cancer among children, sees about 75% of leukemia cases globally [1,2]. Despite high survival rates exceeding 85% for those without relapse, those experiencing relapse face severe prognoses.

…”

The association between HLA and non-Hodgkin lymphoma subtypes, among a transplant-indicated population

“…The human leukocyte antigens (HLAs) are a class of genes encoded in the major histocompatibility complex (MHC) on chromosome 6 that are critical for human immune response. Among the most polymorphic human genes, HLA alleles and haplotypes are increasingly implicated in the etiologies and outcomes of immune conditions and hematopoietic malignancies, including Hodgkin lymphoma [1,2], non-Hodgkin lymphomas (NHLs) [3][4][5][6][7][8][9][10][11], and leukemias [12][13][14][15][16]. Recent genome-wide association studies (GWASs) of NHL have now confirmed the role for HLA in four major NHL subtypes diffuse large B-cell lymphoma (DLBCL) [17,18], follicular lymphoma (FL) etiology [19][20][21], chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) [22][23][24], and marginal zone lymphomas (MZLs) [25].…”