Conserved IKAROS-regulated genes associated with B-progenitor acute lymphoblastic leukemia outcome

Genetic alterations disrupting the transcription factor IKZF1 (encoding IKAROS) are associated with poor outcome in B lineage acute lymphoblastic leukemia (B-ALL) and occur in >70% of the high-risk BCR-ABL1+ (Ph+) and Ph-like disease subtypes. To examine IKAROS function in this context, we have developed novel mouse models allowing reversible RNAi-based control of Ikaros expression in established B-ALL in vivo. Notably, leukemias driven by combined BCR-ABL1 expression and Ikaros suppression rapidly regress when endogenous Ikaros is restored, causing sustained disease remission or ablation. Comparison of transcriptional profiles accompanying dynamic Ikaros perturbation in murine B-ALL in vivo with two independent human B-ALL cohorts identified nine evolutionarily conserved IKAROS-repressed genes. Notably, high expression of six of these genes is associated with inferior event-free survival in both patient cohorts. Among them are EMP1, which was recently implicated in B-ALL proliferation and prednisolone resistance, and the novel target CTNND1, encoding P120-catenin. We demonstrate that elevated Ctnnd1 expression contributes to maintenance of murine B-ALL cells with compromised Ikaros function. These results suggest that IKZF1 alterations in B-ALL leads to induction of multiple genes associated with proliferation and treatment resistance, identifying potential new therapeutic targets for high-risk disease

Early Jurassic palaeoenvironments in the Surat Basin, Australia - marine incursion into eastern Gondwana

Interpretations of palaeodepositional environments are important for reconstructing Earth history. Only a few maps showing the Jurassic depositional environments in eastern Australia currently exist. Consequently, a detailed understanding of the setting of Australia in Gondwana is lacking. Core, wireline logs, two‐dimensional and three‐dimensional seismic from the Precipice Sandstone and Evergreen Formation in the Surat Basin have been used to construct maps showing the evolution of depositional environments through the Early Jurassic. The results indicate the succession consists of three third‐order sequences (Sequence 1 to Sequence 3) that were controlled by eustatic sea level. The lowstand systems tract in Sequence 1 comprises braidplain deposits, confined to a fairway that parallels the basin centre. The strata were initially deposited in two sub‐basins, with rivers flowing in different orientations in each sub‐basin. The transgressive systems tract of Sequence 1 to lowstand systems tract of Sequence 3 is dominated by fluvio–deltaic systems infilling a single merged basin centre. Finally, the transgressive and highstand systems tracts of Sequence 3 show nearshore environments depositing sediment into a shallow marine basin. In the youngest part of this interval, ironstone shoals are the most conspicuous facies, the thickness and number of which increase towards the north and east. This study interprets a corridor to the open ocean through the Clarence–Moreton Basin, or the Carpentaria and Papuan basins, evidence of which has been eroded. These results challenge a commonly held view that eastern Australia was not influenced by eustasy, and propose a more dynamic palaeogeographic setting comprising a mixture of fluvial, deltaic and shallow marine sedimentary environments. This work can be used to unravel the stratigraphic relationships between Mesozoic eastern Australian basins, or in other basins globally as an analogue for understanding the complex interplay of paralic depositional systems in data poor areas

Letter to H.B. Stenzel from J.M. Dickins on 1961-01-18

Jackson School of Geoscience

Letter to H.B. Stenzel from J.M. Dickins on 1959-05-25

Jackson School of Geoscience

First Carboniferous and ?Permian marine macrofaunas from Antarctica and their tectonic implications

The first Carboniferous and ?Permian marine macrofaunas from the Antarctic continent are described from three sites near Mount King, Alexander Island, Antarctic Peninsula. They include bivalves, brachiopods, bryozoans, crinoids, gastropods, a possible monoplacophoran, nautiloids and a possible serpulid or microconchid. Overall the faunas of two localities are Carboniferous in age and compare well with the Levipustula levis Zone of Argentina and eastern Australia, and are of Namurian (Serpukhovian–Bashkirian) age, based mainly on the brachiopod and bryozoan faunas. Less positive brachiopod evidence from a third locality indicates the presence of a linoproductid fauna of possible Carboniferous or Permian (Gzhelian–Artinskian) age, having affinities with the Argentinian Cancrinella fauna. The lithological and structural characteristics of the Mount King beds are comparable to the accretionary complex of the LeMay Group (hitherto of only proven Jurassic–Cretaceous age) of Alexander Island, in which they are provisionally placed. However, the beds may also correlate with the Trinity Peninsula Group (Carboniferous–Triassic) of the northern Antarctic Peninsula. The features of the Mount King beds are consistent with the presence of an accretionery complex related to an island arc in the Late Palaeozoic, but are not necessarily conclusive proof of the presence of such a terrane at that time in what is now Alexander Island