Increased frequency of mannose-binding lectin insufficiency among children with acute lymphoblastic leukemia

Blood ◽  
2002 ◽  
Vol 100 (10) ◽  
pp. 3757-3760 ◽  
Author(s):  
Kjeld Schmiegelow ◽  
Peter Garred ◽  
Birgitte Lausen ◽  
Bente Andreassen ◽  
Bodil Laub Petersen ◽  
...  
Keyword(s):  
Early Childhood ◽  
Acute Lymphoblastic Leukemia ◽  
Odds Ratio ◽  
Lymphoblastic Leukemia ◽  
Mannose Binding Lectin ◽  
Childhood All ◽  
Group Iii ◽  
Group I ◽  
Mannose Binding ◽  
Binding Lectin

Epidemiological data indicate that acute lymphoblastic leukemia (ALL) could be induced by interactions between the immune system and early childhood infections. Mannose-binding lectin (MBL) plays a critical role in the immune response in early childhood before specific immune protection develops. We investigated whether there may be an association between childhood ALL and low-producing MBLgenotypes. Serum MBL levels depend on normal (A)or defective (O) alleles, and on normal (Y) or reduced (X) promoter activities. For this study, 137 noninfants with ALL and 250 controls were classified into 3 MBL genotype groups according to their influence on the serum level of functional MBL: group I, YA/YA andYA/XA (higher levels); group II, XA/XA andYA/O (intermediate levels); and group III, MBLinsufficiency with XA/O or O/O(MBL-deficient) genotypes. Compared with controls, cases more often had low-level genotypes (I/II/III: 63 [46%]/44 [32%]/30 [22%] vs 145 [58%]/65 [26%]/40 [16%];P = .02) and MBL deficiency (8.8% vs 2.8%;P = .009). Thus, the ALL odds ratio forMBL-deficient versus nondeficient individuals was 3.3 (95% CI, 1.3-8.7), whereas the ALL odds ratio for group I versus group II/III genotypes was 0.62 (95% CI, 0.41-0.94). MBL group III patients were significantly younger at diagnosis than patients in group I/II (median, 3.9 vs 5.2 years; P = .04). The study shows that the presence of low-level MBL genotypes is associated with an increased risk of childhood ALL, particularly with early age at onset.

Mannose binding lectin and ficolin-2 polymorphisms are associated with increased risk for bacterial infections in children with B acute lymphoblastic leukemia

2014 ◽  
Vol 61 (6) ◽  
pp. 1017-1022 ◽  
Author(s):  
Zoe Dorothea Pana ◽  
Fekri Samarah ◽  
Rigini Papi ◽  
Charalampos Antachopoulos ◽  
Theodotis Papageorgiou ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Bacterial Infections ◽  
Lymphoblastic Leukemia ◽  
Mannose Binding Lectin ◽  
Increased Risk ◽  
Mannose Binding ◽  
Binding Lectin

scholarly journals Environmental Risk Factors for Childhood Acute Lymphoblastic Leukemia: An Umbrella Review

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 382
Author(s):  
Felix M. Onyije ◽  
Ann Olsson ◽  
Dan Baaken ◽  
Friederike Erdmann ◽  
Martin Stanulla ◽  
...  
Keyword(s):  
Risk Factors ◽  
Early Childhood ◽  
Acute Lymphoblastic Leukemia ◽  
Environmental Risk ◽  
Lymphoblastic Leukemia ◽  
Environmental Risk Factors ◽  
Umbrella Review ◽  
Level Of Evidence ◽  
Childhood All ◽  
High Consumption

Leukemia is the most common type of cancer among children and adolescents worldwide. The aim of this umbrella review was (1) to provide a synthesis of the environmental risk factors for the onset of childhood acute lymphoblastic leukemia (ALL) by exposure window, (2) evaluate their strength of evidence and magnitude of risk, and as an example (3) estimate the prevalence in the German population, which determines the relevance at the population level. Relevant systematic reviews and pooled analyses were identified and retrieved through PubMed, Web of Science databases and lists of references. Only two risk factors (low doses of ionizing radiation in early childhood and general pesticide exposure during maternal preconception/pregnancy) were convincingly associated with childhood ALL. Other risk factors including extremely low frequency electromagnetic field (ELF-MF), living in proximity to nuclear facilities, petroleum, benzene, solvent, and domestic paint exposure during early childhood, all showed some level of evidence of association. Maternal consumption of coffee (high consumption/>2 cups/day) and cola (high consumption) during pregnancy, paternal smoking during the pregnancy of the index child, maternal intake of fertility treatment, high birth weight (≥4000 g) and caesarean delivery were also found to have some level of evidence of association. Maternal folic acid and vitamins intake, breastfeeding (≥6 months) and day-care attendance, were inversely associated with childhood ALL with some evidence. The results of this umbrella review should be interpreted with caution; as the evidence stems almost exclusively from case-control studies, where selection and recall bias are potential concerns, and whether the empirically observed association reflect causal relationships remains an open question. Hence, improved exposure assessment methods including accurate and reliable measurement, probing questions and better interview techniques are required to establish causative risk factors of childhood leukemia, which is needed for the ultimate goal of primary prevention.

Deficiency of Mannose-Binding Lectin Is a Risk Factor for Invasive Pulmonary Aspergillosis in Patients with Multiple Myeloma: An Analysis of 482 Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 667-667 ◽  
Author(s):  
Elias J. Anaissie ◽  
Wei-zhi Zhao ◽  
Yue-Jin Wen ◽  
Monica Grazziutti ◽  
Wen Ling ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Risk Factor ◽  
Cancer Patients ◽  
Odds Ratio ◽  
Invasive Pulmonary Aspergillosis ◽  
Mannose Binding Lectin ◽  
Pulmonary Aspergillosis ◽  
Mannose Binding ◽  
Binding Lectin ◽  
Mbl Deficiency

Abstract Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in neutropenic cancer patients. Mannose-binding lectin (MBL) is a circulating pattern-recognition molecule that recognizes microbial carbohydrate motifs, leading to complement activation, opsonization, phagocytosis, and cell lysis and is considered an important component of innate immunity. Deficiency of MBL is common due to genetic polymorphisms and has been identified as a risk factor for severe infections among myeloma patients undergoing autologous stem cell transplantation (ASCT). MBL deficiency has also been reported as a predisposing factor for chronic necrotizing pulmonary aspergillosis, a locally invasive infection typically seen in patients with chronic lung disease. The association between MBL deficiency in cancer patients and susceptibility to IPA has never been evaluated. This study investigated whether MBL deficiency, as measured by serum MBL levels, is associated with the development of IPA in patients with multiple myeloma undergoing multiple cycles of antineoplastic chemotherapy including tandem ASCT and post-transplant consolidation chemotherapy. Baseline serum MBL level was measured using ELISA. The frequency of IPA was assessed retrospectively in 482 adult myeloma patients (2007–2008), 50 of whom developed IPA. Association between MBL levels and IPA was analyzed using logistic regression analysis (table 1). Patients with normal serum MBL levels (≥ 1000 ng/mL) had significantly fewer episodes of IPA [(21 in 303 patients; 6.9%); Odds ratio, 0.385; 95% CI (0.212–0.699); P = 0.0017] than patients with low (100–999 ng/mL; 18 episodes in 125 patients (14.4%)) and very low (<100 ng/mL) MBL levels (11 episodes in 54 patients; 20.4%) (Table 1). We conclude that MBL deficiency is associated with more frequent episodes of IPA among patients with myeloma undergoing intensive antineoplastic therapy including ASCT and should be added to the list of risk factors for chemotherapy-related IPA. Baseline MBL level may serve as a predictor for the risk of IPA among such patients. This novel finding may have important therapeutic implications because recombinant Human MBL replacement therapy is now available and could therefore be applied prophylactically to decrease the risk of IPA in MBL-deficient patients receiving chemotherapy. Table 1. Association between serum MBL level and risk of invasive pulmonary aspergillosis (482 pts) Aspergillosis MBL (ng/mL) No (n=432) Yes (n=50) Rate Odds ratio (95%C.I.) P-value <100 43 (10%) 11 (22%) 11/54 (20% ) Reference Reference 100–1000 107 (25%) 18 (36%) 18/125 (14%) 0.658 (0.287–1.507) 0.3218 1000 282 (65%) 21 (42%) 21/303 (7%) 0.291 (0.131–0.646) 0.0024 MBL <1000 150 (35%) 29 (58%) 29/179 (16%) Reference

scholarly journals Insights into the prenatal origin of childhood acute lymphoblastic leukemia

2020 ◽  
Vol 39 (1) ◽  
pp. 161-171 ◽  
Author(s):  
Daniel Hein ◽  
Arndt Borkhardt ◽  
Ute Fischer
Keyword(s):  
Early Childhood ◽  
Acute Lymphoblastic Leukemia ◽  
Gene Fusion ◽  
Lymphoblastic Leukemia ◽  
Chromosomal Translocations ◽  
Gene Fusions ◽  
Leukemic Transformation ◽  
Childhood All ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Cells Of Origin

AbstractPediatric acute lymphoblastic leukemia (ALL) is defined by recurrent chromosomal aberrations including hyperdiploidy and chromosomal translocations. Many of these aberrations originate in utero and the cells transform in early childhood through acquired secondary mutations. In this review, we will discuss the most common prenatal lesions that can lead to childhood ALL, with a special emphasis on the most common translocation in childhood ALL, t(12;21), which results in the ETV6-RUNX1 gene fusion. The ETV6-RUNX1 fusion arises prenatally and at a 500-fold higher frequency than the corresponding ALL. Even though the findings regarding the frequency of ETV6-RUNX1 were originally challenged, newer studies have confirmed the higher frequency. The prenatal origin has also been proven for other gene fusions, including KMT2A, the translocations t(1;19) and t(9;22) leading to TCF3-PBX1 and BCR-ABL1, respectively, as well as high hyperdiploidy. For most of these aberrations, there is evidence for more frequent occurrence than the corresponding leukemia incidences. We will briefly discuss what is known about the cells of origin, the mechanisms of leukemic transformation through lack of immunosurveillance, and why only a part of the carriers develops ALL.

scholarly journals Unravelling an HLA-DR Association in Childhood Acute Lymphoblastic Leukemia

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 694-700 ◽  
Author(s):  
M. Tevfik Dorak ◽  
Tom Lawson ◽  
Helmut K.G. Machulla ◽  
Chris Darke ◽  
Ken I. Mills ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genetic Risk ◽  
Odds Ratio ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Allelic Association ◽  
Hla Association ◽  
Childhood All ◽  
Mouse Leukemia ◽  
Hla Dr

Abstract Genetic and environmental factors play an interactive role in the development of childhood acute lymphoblastic leukemia (ALL). Since the demonstration of a major histocompatibility complex (MHC) influence on mouse leukemia in 1964, an HLA association has been considered as a possible genetic risk factor. Despite extensive efforts, however, no strong evidence comparable to the H-2k influence on mouse leukemia has been shown. The number of negative serological studies resulted in a loss of interest and consequently, no molecular HLA-DR association study has been published to date. We reconsidered the HLA-DR association in childhood ALL in 114 patients from a single center and 325 local newborn controls by polymerase chain reaction (PCR) analysis of the HLA-DRB1/3/4/5 loci. With conventional analysis, there was a moderate allelic association with the most common allele in the HLA-DR53 group, HLA-DRB1*04, in the whole group that was stronger in males (P = .0005, odds ratio = 2.9). When the other expressed HLA-DRB loci were examined, homozygosity for HLA-DRB4*01, encoding the HLA-DR53 specificity, was increased in patients (21.1%v 8.3%; odds ratio = 2.9, P = .0005). Consideration of gender showed that all of these associations were reflections of a male-specific increase in homozygosity for HLA-DRB4*01 (32.8% v 4.0%; odds ratio = 11.7, 95% confidence interval [CI] = 4.9 to 28.0; P = 3 × 10−8). This highly significant result provided the long-suspected evidence for the HLA-DR influence on the development of childhood ALL while confirming the recessive nature of the MHC influence on human leukemogenesis as in experimental models. The cross-reactivity between HLA-DR53 and H-2Ek, extensive mimicry of the immunodominant epitope of HLA-DR53 by several carcinogenic viruses, and the extra amount of DNA in the vicinity of the HLA-DRB4 gene argue for the case that HLA-DRB4*01 may be one of the genetic risk factors for childhood ALL.

scholarly journals Unravelling an HLA-DR Association in Childhood Acute Lymphoblastic Leukemia

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 694-700 ◽  
Author(s):  
M. Tevfik Dorak ◽  
Tom Lawson ◽  
Helmut K.G. Machulla ◽  
Chris Darke ◽  
Ken I. Mills ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genetic Risk ◽  
Odds Ratio ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Allelic Association ◽  
Hla Association ◽  
Childhood All ◽  
Mouse Leukemia ◽  
Hla Dr

Genetic and environmental factors play an interactive role in the development of childhood acute lymphoblastic leukemia (ALL). Since the demonstration of a major histocompatibility complex (MHC) influence on mouse leukemia in 1964, an HLA association has been considered as a possible genetic risk factor. Despite extensive efforts, however, no strong evidence comparable to the H-2k influence on mouse leukemia has been shown. The number of negative serological studies resulted in a loss of interest and consequently, no molecular HLA-DR association study has been published to date. We reconsidered the HLA-DR association in childhood ALL in 114 patients from a single center and 325 local newborn controls by polymerase chain reaction (PCR) analysis of the HLA-DRB1/3/4/5 loci. With conventional analysis, there was a moderate allelic association with the most common allele in the HLA-DR53 group, HLA-DRB1*04, in the whole group that was stronger in males (P = .0005, odds ratio = 2.9). When the other expressed HLA-DRB loci were examined, homozygosity for HLA-DRB4*01, encoding the HLA-DR53 specificity, was increased in patients (21.1%v 8.3%; odds ratio = 2.9, P = .0005). Consideration of gender showed that all of these associations were reflections of a male-specific increase in homozygosity for HLA-DRB4*01 (32.8% v 4.0%; odds ratio = 11.7, 95% confidence interval [CI] = 4.9 to 28.0; P = 3 × 10−8). This highly significant result provided the long-suspected evidence for the HLA-DR influence on the development of childhood ALL while confirming the recessive nature of the MHC influence on human leukemogenesis as in experimental models. The cross-reactivity between HLA-DR53 and H-2Ek, extensive mimicry of the immunodominant epitope of HLA-DR53 by several carcinogenic viruses, and the extra amount of DNA in the vicinity of the HLA-DRB4 gene argue for the case that HLA-DRB4*01 may be one of the genetic risk factors for childhood ALL.

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