Description: Sub-micron marine aerosol particles (PM1) were collected during the MERIAN cruise MSM 18/3 between 22 June 2011 and 21 July 2011 from the Cape Verde island Sao Vicente to Gabun crossing the tropical Atlantic Ocean and passing equatorial upwelling areas. According to air mass origin and chemical composition of the aerosol particles, three main regimes could be established. Aerosol particles in the first part of the cruise were mainly of marine origin, in the second part was marine and slightly biomass burning influenced (increasing tendency) and in the in last part of the cruise, approaching the African mainland, biomass burning influences became dominant. Generally aerosols were dominated by sulfate (caverage = 1.99 µg/m**3) and ammonium ions (caverage = 0.72 µg/m**3) that are well correlated and slightly increasing along the cruise. High concentrations of water insoluble organic carbon (WISOC) averaging 0.51 µg/m**3 were found probably attributed to the high oceanic productivity in this region. Water soluble organic carbon (WSOC) was strongly increasing along the cruise from concentrations of 0.26 µg/m**3 in the mainly marine influenced part to concentrations up to 3.3 µg/m**3 that are probably caused by biomass burning influences. Major organic constituents were oxalic acid, methansulfonic acid (MSA) and aliphatic amines. MSA concentrations were quite constant along the cruise (caverage = 43 ng/m**3). While aliphatic amines were more abundant in the first mainly marine influenced part with concentrations of about 20 ng/m**3, oxalic acid showed the opposite pattern with average concentrations of 12 ng/m**3 in the marine and 158 ng/m**3 in the biomass burning influenced part. The alpha dicarbonyl compounds glyoxal and methylglyoxal were detected in the aerosol particles in the low ng/m**3 range and followed oxalic acid closely. MSA and aliphatic amines accounted for biogenic marine (secondary) aerosol constituents whereas oxalic acid and the alpha dicarbonyl compounds were believed to result mainly from biomass burning. N-alkane concentrations increased along the cruise from 0.81 to 4.66 ng/m**3, PAHs and hopanes were abundant in the last part of the cruise (caverage of PAHs = 0.13 ng/m**3, caverage of hopanes = 0.19 ng/m**3). Levoglucosan was identified in several samples of the last part of the cruise in concentrations around 2 ng/m**3, pointing to (aged) biomass burning influences. The investigated organic compounds could explain 9.5% of WSOC in the mainly marine influenced part (dominating compounds: aliphatic amines and MSA) and 2.7% of WSOC in the biomass burning influenced part (dominating compound: oxalic acid) of the cruise.

Description: Aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL) are advanced hematopoietic neoplasms with poor prognosis. In these patients, neoplastic mast cells (MCs) are resistant against various drugs. We examined the effects of 2 demethylating agents, 5-azacytidine and decitabine on growth and survival of neoplastic MCs and the MC line HMC-1. Two HMC-1 subclones were used, HMC-1.1 lacking KIT D816V and HMC-1.2 exhibiting KIT D816V. Both agents induced apoptosis in HMC-1.1 and HMC-1.2 cells. Decitabine, but not 5-azacytidine, also produced a G 2 /M cell-cycle arrest in HMC-1 cells. Drug-induced apoptosis was accompanied by cleavage of caspase-8 and caspase-3 as well as FAS- demethylation and FAS–re-expression in neoplastic MCs. Furthermore, both demethylating agents were found to synergize with the FAS-ligand in inducing apoptosis in neoplastic MCs. Correspondingly, siRNA against FAS was found to block drug-induced expression of FAS and drug-induced apoptosis in HMC-1 cells. Neither 5-azacytidine nor decitabine induced substantial apoptosis or growth arrest in normal MCs or normal bone marrow cells. Together, 5-azacytidine and decitabine exert growth-inhibitory and proapoptotic effects in neoplastic MCs. These effects are mediated through "FAS–re-expression" and are augmented by the FAS-ligand. Whether epigenetic drugs produce antineoplastic effects in vivo in patients with ASM and MCL remains to be determined.

Description: Chronic myeloid leukemia (CML) is a stem cell (SC) neoplasm characterized by the BCR/ABL1 oncogene. Although mechanisms of BCR/ABL1-induced transformation are well-defined, little is known about effector-molecules contributing to malignant expansion and the extramedullary spread of leukemic SC (LSC) in CML. We have identified the cytokine-targeting surface enzyme dipeptidylpeptidase-IV (DPPIV/CD26) as a novel, specific and pathogenetically relevant biomarker of CD34 + /CD38 CML LSC. In functional assays, CD26 was identified as target enzyme disrupting the SDF-1-CXCR4-axis by cleaving SDF-1, a chemotaxin recruiting CXCR4 + SC. CD26 was not detected on normal SC or LSC in other hematopoietic malignancies. Correspondingly, CD26 + LSC decreased to low or undetectable levels during successful treatment with imatinib. CD26 + CML LSC engrafted NOD-SCID-IL-2R –/– (NSG) mice with BCR/ABL1 + cells, whereas CD26 SC from the same patients produced multilineage BCR/ABL1 – engraftment. Finally, targeting of CD26 by gliptins suppressed the expansion of BCR/ABL1 + cells. Together, CD26 is a new biomarker and target of CML LSC. CD26 expression may explain the abnormal extramedullary spread of CML LSC, and inhibition of CD26 may revert abnormal LSC function and support curative treatment approaches in this malignancy.