Definition of a possible genetic basis for susceptibility to acute myelogenous leukemia associated with the presence of a polymorphic Ia epitope.

Seremetis, Stephanie; Cuttner, Janet; Winchester, Robert

doi:10.1172/jci112115

Cited by 25 publications

(14 citation statements)

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“…Interestingly, a gender effect which was opposite to that observed in childhood acute lymphoblastic leukaemia was noted. Overall, this study extended earlier observations that susceptibility to AML (Seremetis et al, 1985), ALL (Dorak et al, 1995), CML (Dorak et al, 1994~) and CLL (Dyer et al, 1986) is associated with HLA-DR53. Furthermore, a significant protective effect of DR52 was also established.…”

Section: Discussionsupporting

confidence: 90%

“…The initial serological studies uncovered some associations but did not establish a strong and consistent influence of HLA antigens on the development of neoplasms (Tiwari and Terasaki, 1985). The haemopoietic malignancies have been the most extensively studied ones (Seremetis et al, 1985;Bortin et al, 1987;Caruso et al, 1987;Richter et al, 1973;Nunez-Roldan et al, 1982; Kilpatrick et al, 1984;Dyer et al, 1986;Cuttner et al, 1994). In leukaemia and lymphoma also, no consistent HLA association has been shown by serology.…”

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confidence: 99%

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Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia

et al. 1996

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The major histocompatibility complex is one of the interactive factors in the multifactorial model of carcinogenesis. Its main influence in experimental models is on the age at onset of malignancies. We have previously shown a similar effect of homozygosity for HLA-DR53 in CML. In the present study, we investigated 79 patients with CLL and 329 local controls from Germany. In addition to full serotyping, all patients and I I 6 of controls were also typed by HU-DR6 PCR analysis. The homozygosity rates for DR53 in patients under and over the median age (60 years) were 18.6% and 2.9%, respectively ( p = 0.03). In experimental models, the major histocompatibility complex (MHC) has an interactive influence on the development of spontaneous, virally or chemically-induced malignancies (Lilly et al., 1964; Boyse et al., 1972;Faraldo et al., 1979;Oomen et al., 1988;Vasmel et al., 1988). Particular alleles of this polymorphic system influence the incidence and phenotype, as well as the age at onset of malignancies (Vasmel et al., 1988;Miyazawa et al., 1992). The interaction of the MHC is not exerted on transformation of a neoplastic clone but occurs during the pre-leukaemic stage (Chesebro, 1981;Lonai et al., 1982). Thus, it does not contain essential susceptibility genes but influences the rate of progression to overt malignancy. More than one MHC gene is involved in the complex, multifactorial development of malignancies (Oomen et al., 1988;Zijlstra and Melief, 1986). Eight of theThe findings in animal models stimulated similar studies investigating the role of the human MHC (HLA complex) in malignancies. The initial serological studies uncovered some associations but did not establish a strong and consistent influence of HLA antigens on the development of neoplasms (Tiwari and Terasaki, 1985). The haemopoietic malignancies have been the most extensively studied ones (Seremetis et al., 1985;Bortin et al., 1987;Caruso et al., 1987;Richter et al., 1973;Nunez-Roldan et al., 1982; Kilpatrick et al., 1984;Dyer et al., 1986;Cuttner et al., 1994). In leukaemia and lymphoma also, no consistent HLA association has been shown by serology.With the advent of molecular typing methods, this issue has been revisited. Recent studies have shown stronger allelic associations, although genotypes, age and gender effect have usually been overlooked (Apple et al., 1994;Klitz et al., 1994). The first DNA-based study investigating the role of the HLA complex in the development of leukaemia showed a strong influence of several independent genotypes on the age at onset of chronic myeloid leukaemia (CML), the strongest one being homozygosity for the supertypic specificity HLA-DR53 (Dorak et al., 1994a). A second molecular study confirmed the role of this homozygous genotype in increased susceptibility to childhood acute lymphoblastic leukaemia (ALL) and also showed a gender effect (Dorak et al., 1995).In the present study, the same association and its influence on the age at onset of chronic lymphoid leukaemia (CLL) were investigated by DNA analy...

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia

et al. 1996

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“…The SNP near the HLA-DRA gene, rs2395185, is a marker for the HLA-DRB4 (DR53) lineage [23]. The HLA-DRB4 lineage or its marker SNP have been previously shown as a risk marker in lung cancer [27], asthma [29], rheumatoid arthritis [28], type I diabetes [44], adult acute myeloblastic leukemia [45], chronic myeloid leukemia [46], chronic lymphoid leukemia [47][48][49] and in childhood ALL (males only) [24,50,51], and as a protective marker for non-Hodgkin lymphoma [26], and ulcerative colitis [30][31][32]52]. The DRB4/DR53 lineage has been shown previously to have a risk association with childhood ALL, with male specificity, within a European sample via HLA typing [24].…”

Section: Discussionmentioning

confidence: 99%

Genetic markers in a multi-ethnic sample for childhood acute lymphoblastic leukemia risk

Kennedy¹,

Kamdar²,

Lupo³

et al. 2014

Leukemia & Lymphoma

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Genome-wide association studies have identified multiple risk loci for childhood acute lymphoblastic leukemia (ALL), but mostly in European/White populations despite Hispanics having a greater risk. We re-examined SNPs of known associations with childhood ALL and known HLA region lymphoma risk markers in a multi-ethnic population. Significant associations were found in two ARID5B variants (rs7089424 and rs10821936). We replicated a strong risk association in non-Hispanic White males with rs2395185, a protective marker for lymphoma.Another HLA region marker, rs2647012, showed a risk association among Hispanics only, while a strong protective association was found with rs1048456, a follicular lymphoma risk marker.Our study validated this new case-control sample by confirming genetic markers associated with childhood ALL, and yielded new associations with lymphoma markers. Despite positive results, our study did not provide any clues to why Hispanics have a higher susceptibility to childhood leukemia, suggesting that environmental factors may have a strong contribution.

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“…The SNP near the HLA-DRA gene, rs2395185, is a marker for the HLA-DRB4 (DR53) lineage [38]. The HLA-DRB4 lineage or its marker SNP have been previously shown as a risk marker in lung cancer [39], asthma [40], rheumatoid arthritis [49], type I diabetes [48], adult acute myeloblastic leukemia [61], chronic myeloid leukemia [62], chronic lymphoid leukemia [63][64][65] and in childhood ALL (males only) [46,66,67], and as a protective marker for non-Hodgkin lymphoma [41], and ulcerative colitis [42][43][44]47]. The DRB4/DR53 lineage has been shown previously to have a risk association with childhood ALL, with male specificity, within a European sample via HLA typing [46].…”

Section: Discussionmentioning

confidence: 99%

“…Cell studies have shown that B-lymphoid cell lines that are homozygous for the C282Y variant demonstrate greater iron uptake and increased cell sensitivity to oxidative stress [59]. The increase in oxidative stress due to the high iron levels may increase radiation sensitivity, which has been shown to increase cancer susceptibility [60,61]. Lymphocytes can be radiation sensitized by iron, and…”

Section: Chitambar Et Al Have Suggested That Increased Intracellularmentioning

confidence: 99%

Genetic Markers, Birth Characteristics, and Childhood Leukemia Risk

Kennedy¹

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Definition of a possible genetic basis for susceptibility to acute myelogenous leukemia associated with the presence of a polymorphic Ia epitope.

Cited by 25 publications

References 41 publications

Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia

Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia

Genetic markers in a multi-ethnic sample for childhood acute lymphoblastic leukemia risk

Genetic Markers, Birth Characteristics, and Childhood Leukemia Risk

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