SCITE Assistant (AI) Fields a Genomic AML Question

 SCITE is a subscription service that is a big like PubMed on nuclear-powered AI steroids.  One function seaerches a paper's bibliography in detail.  Another function searches citations to it.   Functions like "mind maps" or "clouds" of visually related citations are available.

SCITE also includes a tailored AI service geared to citations.   It can produce a dozen or more citations in response to tailored question.  Unlike PubMed, it can provide these in an "essay" like format, with citations hotlinked in short sections of text that explain what that paper provides.   Meanwhile, in a right-hand side bar, you can see roughly 50-word extracts from that paper (assuming full text is online), then a hotlink to the full reference of the paper.   This right-hand column marches down the screen with paper by paper  detailed data, matching each citations hot-linked in the "essay" response.

This ability to show 50-word snippets of why a citation is relevant - from either abstract or often from full text - is a unique power brought to us by SCITE.

The "essay" is an AI format.  It's not perfect and may make mistakes.  Also, in the example provided, which is obscure, the most recent citation was 2018.   (Normally, it handles citation up to about 12 months ago).   But you may find this essay format is an advantageous starting place, as opposed to a 30-paper titles list you make get from PubMed.   

Here I show a screen shot from the top of a SCITE ASSISTANT response to a question about genomics of AML.   Then, I cut and paste the "essay" format of its reponse.   

click to enlarge

Note, online, the essay citations were hotlinks.

Show me recent papers that demonstrate an association between acute myeloid leukemia and chromothripsis, which means massive genome disruption.

Recent papers have demonstrated an association between acute myeloid leukemia (AML) and chromothripsis, which is a phenomenon characterized by massive genome disruption (Fontana et al., 2018). Chromothripsis is a catastrophic event that involves the disruption of one or a few chromosomes into multiple fragments, followed by random rejoining and repair (Fontana et al., 2018).

 A study by Fontana et al. (2018) investigated the incidence of chromothripsis in 395 newly diagnosed adult AML patients and its impact on survival. The study utilized SNP 6.0 or CytoscanHD Array to analyze the genomic background of AML patients (Fontana et al., 2018). The results of this study indicated that chromothripsis is a non-anecdotal finding in AML and is associated with higher age and lower white blood cell count at diagnosis. Furthermore, chromothripsis was found to be mutually exclusive with FLT3 and NPM1 mutations Fontana et al. (2018).

 In addition to chromothripsis, other genomic instability mechanisms have been implicated in AML. Cagnetta et al. (2017) demonstrated that SIRT6, a NAD+-dependent nuclear deacetylase, functions as a genome guardian by preserving DNA integrity in AML cells. The study showed that depletion of SIRT6 enzymatic activity increased the vulnerability of AML cells to DNA-damaging agents (Cagnetta et al., 2017).

 Furthermore, Sukhai et al. (2012) identified lysosomal disruption as a potential therapeutic strategy for AML. The study screened a library of drugs and found that the antimalarial agent mefloquine selectively killed AML cells and AML stem cells. The researchers demonstrated that mefloquine disrupts lysosomes, permeabilizes the lysosome membrane, and releases cathepsins into the cytosol (Sukhai et al., 2012). These findings provide a rationale for testing lysosomal disruption as a novel therapeutic strategy for AML (Sukhai et al., 2012).

 Another study by Puram et al. (2016) investigated the role of core circadian clock genes in AML. The researchers conducted RNA interference screens and identified Clock and Bmal1 as essential transcription factors for the growth of AML cells. Disruption of the canonical circadian pathway components impaired proliferation, enhanced myeloid differentiation, and depleted leukemia stem cells (Puram et al., 2016). However, genomic data from The Cancer Genome Atlas (TCGA) indicated that central circadian components are intact in AML (Puram et al., 2016).

 In summary, recent papers have provided evidence for an association between AML and chromothripsis, as well as other genomic instability mechanisms such as SIRT6 dysregulation and lysosomal disruption. Understanding these molecular mechanisms can contribute to the development of targeted therapies for AML.

 References:

Cagnetta, A., Soncini, D., Orecchioni, S., Talarico, G., Minetto, P., Guolo, F., … & Cea, M. (2017). Depletion of sirt6 enzymatic activity increases acute myeloid leukemia cells’ vulnerability to dna-damaging agents. Haematologica, 103(1), 80-90. https://doi.org/10.3324/haematol.2017.176248

Fontana, M., Marconi, G., Feenstra, J., Fonzi, E., Papayannidis, C., Rorà, A., … & Martinelli, G. (2018). Chromothripsis in acute myeloid leukemia: biological features and impact on survival. Leukemia, 32(7), 1609-1620. https://doi.org/10.1038/s41375-018-0035-y

Puram, R., Kowalczyk, M., Boer, C., Schneider, R., Miller, P., McConkey, M., … & Ebert, B. (2016). Core circadian clock genes regulate leukemia stem cells in aml. Cell, 165(2), 303-316. https://doi.org/10.1016/j.cell.2016.03.015

Sukhai, M., Prabha, S., Hurren, R., Rutledge, A., Lee, A., Sriskanthadevan, S., … & Schimmer, A. (2012). Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors. Journal of Clinical Investigation, 123(1), 315-328. https://doi.org/10.1172/jci64180