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Background and Aims The biological characterization of childhood acute myeloid leukemia (c-AML) is an important outcome predictor. In Brazil, very little is known about the frequency of AML subgroups, although c-AML accounts for about 18% of leukemias. We carried out this study to investigate the contribution of type I and II gene mutations in the probability of overall survival (pOS) of c-AML in Brazil. Methods Seven hundred and three de novo pediatric AML cases (2000–2015) were assessed throughout a multicentric network study. Mutations in hotspot regions of FLT3 , NRAS , KRAS , PTPN11 , and c- KIT genes were analyzed as well as fusion genes ( RUNX1 - RUNX1T1 , MLL / KMT2A -r, CBFβ - MYH11 , and PML - RARα ) associated with AML. Patients were treated out of the clinical trial although following the BFM-AML2004 protocol. Acute promyelocytic leukemia (APL) was treated differently. AML with Down syndrome was excluded. Results There were significant differences in gene mutations among age ranges (≤2 years-old; >2–10 years old and ≥11 years old) and the nonrandom association between type I/II mutations. Lower white blood cell count (≤50 × 10 9 /L) was associated with RUNX1 - RUNX1T1 , whereas higher WBC with CBFβ-MYH11 ( p p = 0.03). pOS differences were observed between Brazilian regions. The South-Southeast regions had a better 5-year pOS, whereas the Midwest region presented the poorest pOS (23.7 ± 4.9%). PTPN11 mutations conferred an adverse prognosis as an independent prognostic factor. Conclusions Identification of genetic subgroups contributes to the molecular epidemiology and biology of AML worldwide, reflecting the profile of pediatric AML cases in Brazil.

The understanding of leukemogenesis in early-age acute leukemia (EAL) has improved remarkably. Initiating somatic mutations detected in dried neonatal blood spots (DNBS) and in cord blood samples of affected children with leukemia have been proven to be acquired prenatally. However, to date, few epidemiological studies have been carried out exploring EAL that include infants and children 13–24 months of age at the diagnosis. Maternal exposure to transplacental DNA-damaging substances during pregnancy has been suggested to be a risk factor for EAL. Most cases of infants with acute lymphoblastic (i-ALL) or myeloid leukemia (i-AML) have KMT2A gene rearrangements ( KMT2A-r ), which disturb its essential role as an epigenetic regulator of hematopoiesis. Due to the short latency period for EAL and the fact that KMT2A-r resembles those found in secondary AML, exposure to topoisomerase II inhibitors has been associated with transplacental risk as proxi for causality. EAL studies have been conducted in Brazil for over two decades, combining observational epidemiology, leukemia biology, and clinical data. EAL was investigated considering (i) age strata (infants vs. 13–24 months-old); (ii) somatic mutations associated with i-ALL and i-AML; (iii) ethnic-geographic variations; (iv) contribution of maternal genotypes; and (v) time latency of exposures and mutations in DNBS. Interactions of acquired and constitutive gene mutations are challenging tools to test risk factor associations for EAL. In this review we summarize the EAL scenario (including B-cell precursor-ALL, T-ALL, and AML) results combining environmental and genetic susceptibility risk factors and we raise questions that should be considered for further action.

The Saldanha hydrothermal field is hosted atop a mafic–ultramafic seamount, located at a non-transform offset on the Mid-Atlantic Ridge. Previous observations revealed a field where transparent low-temperature fluids discharge through centimeter-sized vents without the formation of chimney structures. We present geochemical and stable isotope (O and C) analyses from sediment samples collected at this field, both at and far from the vent area. Most sediments, including some directly adjacent to orifice vents, are pelagic oozes with only a weak hydrothermal overprinting. Hydrothermal precipitates are characterized by Fe–Mn oxyhydroxides and a minor amount of Cu–Zn sulphide minerals. However, one of the cores (SCD7) collected at the vent area shows a much stronger hydrothermal signature. This core is composed of a matrix of serpentine + talc ± chlorite with high porosity, where calcite + chalcopyrite + sphalerite/wurtzite ± pyrite–pyrrhotite were precipitated. In this core, metal enrichments, REE patterns, and the oxygen and carbon isotope composition of calcites indicate that mineralization must have occurred in the subsurface by high-temperature fluids, with minor mixing with seawater and with a significant magmatic contribution. Thus, while most samples confirm previous findings indicating that Saldanha hydrothermal fluid discharge is mainly diffuse and of low temperature, data from core SCD7 suggest that areas of high-temperature hydrothermal activity also occur, where temperatures of the fluids could reach > 260 °C and maximum temperatures of 330 °C. We suggest that fluids can flow through faults at the top of the mount and discharge in a more focused way through vent orifices, producing intense hydrothermal alteration of the sediments. At these locations complex hydrothermal processes occur, including reactions of the hydrothermal fluids with mafic and ultramafic rocks and magma degassing, as suggested by the carbon isotope composition of hydrothermal calcites. The high temperature of the fluid inferred from the geochemistry of the hydrothermal minerals requires a significant heat input to the system, suggesting an additional magmatic heat source to the already proposed exothermic serpentinization reactions.

The Saldanha hydrothermal field is positioned on the top of a seamount located in a non-transform offset (NTO5) on the Mid-Atlantic Ridge (MAR). This hydrothermal system was first described as a low-temperature diffuse field, driven by peridotite–seawater reactions following the detection of high concentrations of CH4 and H2 in the water column, and the occurrence of serpentinite outcrops in the vent area. We have studied the geochemistry and isotopic composition of sediment and rock samples collected across the area and show that hydrothermal circulation at Saldanha is complex and spatially variable, comprising areas of low-temperature diffuse flow but also more focused higher-temperature venting zones. While most sediment samples have an isotopic composition that is similar to normal pelagic sediments, one core (SCD7) show significant hydrothermal influence, sulphide mineralization, non-radiogenic Pb and radiogenic Nd isotope ratios and positive Eu anomalies. This is best explained by mineral precipitation from high-temperature hydrothermal fluids that have circulated through mafic rocks. The host rock lithology and alteration is also highly variable and comprises both fresh basalts, serpentinites and hydrothermally altered rocks (metabasalts, metagabbros and steatites). Serpentinites have REE patterns and eNd(0) values that fall between seawater and mantle peridotite reference values, resulting from extensive interaction of seawater with the original peridotite. This process was probably favoured by the deeply penetrating and long-lived faults occurring at this NTO. Steatites have a positive Eu anomaly and non-radiogenic Pb isotopic values. These signatures, together with the sulphide mineralisation and the extensive Si input necessary for steatization of serpentinites, imply that higher-temperature hydrothermal fluids reacted with gabbroic intrusions at depth. The more hydrothermally altered sediment and rock samples appear to be associated with the Saldanha fault network that promotes a more focused fluid flow and thus enhances hydrothermal alteration within a region of low-temperature diffuse flow.

Hydrothermal sediment mineralogy and geochemistry can provide insights into seafloor mineralization processes and changes through time. We report a geochemical investigation of a short (22 cm) near-vent hydrothermal metalliferous sediment core from the Lucky Strike site (LS), on the Mid-Atlantic Ridge (MAR). The sediment was collected from the base of an active white smoker vent and comprises pure hydrothermal precipitates, mainly chalcopyrite, sphalerite, pyrite and barite, with negligible detrital and biogenic inputs. Geochemically, the core is enriched in elements derived from high-temperature hydrothermalism (Fe, Cu, Zn and Ba) and depleted in elements derived from low-temperature hydrothermalism (Mn), and metasomatism (Mg). The U/Fe content ratio is elevated, particularly in the deeper parts of the core, consistent with uptake from seawater associated with sulphide alteration. Rare earth elements (REE) concentrations are low and chondrite-normalized patterns are characteristic of high-temperature vent fluids with an enrichment in light REE and a pronounced positive Eu anomaly. A stronger positive Eu anomaly associated with higher La n /Sm n at the core top is controlled by barite precipitation. The hydrothermal influence on the REE decreases downcore with some evidence for a stronger seawater influence at depth. Nd isotopes also exhibit an increased detrital/seawater influence downcore. Pb isotope ratios are uniform and plot on the Northern Hemisphere Reference Line in a small domain defined by LS basalts and exhibit no detrital or seawater influence. Lucky Strike sediments are derived from high-temperature mineralization and are overprinted by a weak seawater–sediment interaction when compared with other Atlantic hydrothermal sites such as TAG. The larger seawater input and/or a larger detrital contribution in deeper layers can be explained by variable hydrothermal activity during sediment formation, suggesting different pulses in activity of the LS hydrothermal system.