Malevolent Designer News - Scientists Have Disovered the Sneaky Way Creationism's Putative Designer Created Childhood Leukaemia

Pediatric oncology: Scientists discover new Achilles heel of leukemia cells | Current news from the Goethe University Frankfurt

In leukemia, white blood cells divide uncontrollably.

Acute myeloid leukaemia, micrograph

Pediatric oncology: Scientists discover new Achilles heel of leukemia cells | Current news from the Goethe University Frankfurt

With the double-think that characterises creationsm, creationists will use, depending on what facts they are disputing, two mutually exclusive arguments:

1. A combination of the argument from ignorant incredulity and the false dichotomy fallacy. This argument depends on the assumption that there is only one supernatural entity capable of creating something as complex as DNA, with the conclusion "Therefore, God did it!", which of course is also a non-sequitur and an intellectually dishonest presupositional invocation of something unproven as evidence that it exists.
2. On another day, presented with something so patently evil as childhood cancer or nasty parasites that kill many and make life a misery for millions more (and not just humans, but just about every living thing) creationists invoke somethign called 'Sin' as being responsible for its design and/or creation.
   

In other words, they will argue both that their god is the only entity capable of creating anything, and that 'Sin' can create things too; and their supposedly omnipotent god is powerless to prevent it.

So, it will be interesting to see what arguments creationists will come up with to counter the argument that, if creationism has any substance, the same designer must have designed childhood leukaemia, in full knowledge of the suffering and grief it would cause not just to the child but to his/her parents and relatives.

But I suppose they could always cite William Lane Craig's repugnant defence of religiously-inpired infanticide - "killing children is not wrong because they go straight to heaven so it makes them happy".

But whatever excuse they make, creationists are hoist by their own petard in arguing the false dichotomy fallacy, so they are stuck with portrying the god they purport to worship as the designer of childhood leukaemia - a position they seem to prefer to having people accept that evolution by natural selection is responsible for the nastiness in nature as well as the wonderful.

So, given that a favourite subject for their argument from ignorant incredulity, is the structure of DNA, how will creationists react to the fact that a team of researchers from the Department of Pediatrics and the Institute for Experimental Pediatric Hematology and Oncology at Goethe University, Frankfurt, Germany has discovered a site in the DNA of cancer cells that is essential for leukemia cells to survive?

The DNA in question codes for a sequence of 'non-coding' RNA. Non-coding RNA is a legnth of RNA, trascribed from the DNA template, which, unlike messenger RNA (mRNA) is not a template for a protein, but carries out some other, usually regulatory, function in the cell. This particular RNA sequence normally regulates cell replication and it is cell replication that goes wrong in acute myeloid leukeamia (AML).

AML is the second most common leukemia in children, accounting for around four percent of all malignant diseases in childhood and adolescence. Despite intensive chemotherapy, only around half of those affected survive without relapsing. About one third of children are dependent on a stem cell donation. Since non-specific chemotherapies have severe side effects, there is an urgent need to find new and specific therapeutic approaches.

The Goethe University team firstly identified all the genes responsible for creating 'long non-coding' RNA (lncRNA) and by blocking each in turn found that blocking the gene MYNRL15 was the most effective at preventing the cancer cells from replicating. They found that modifying this gene caused the stem-cells that produce the cancerous white cells to stop producing them and eventually to die.

But there was a surprise.

It wan't stopping the production if the lncRNA that caused the cell to die but the physical alteration of the DNA, particularly its three-dimensional structure. This also prevented nearby genes from expressing and it was this that killed the cell, so the team believe they have found the Achilles heel of childhood AML, and need to concentrate their efforts on gene therapy to hit the cancer at this weakspot.

The team have published their findings, open access, in iScience. Their research is also explained in a press release from Goethe University:

A team led by Jan-Henning Klusmann from the Department of Pediatrics and Dirk Heckl from the Institute for Experimental Pediatric Hematology and Oncology at Goethe University Frankfurt has now discovered an unusual “Achilles heel” in AML cells. For their study, which has now been published, they looked at a specific group of nucleic acids in leukemia cells: noncoding RNAs. Just like regular messenger RNAs (mRNAs), these are produced through gene transcription. However, unlike mRNAs, noncoding RNAs are not translated into proteins but instead often assume regulatory functions, for example in cell growth and cell division. A typical characteristic of cancer cells is a massive disruption of regulatory processes. This makes noncoding RNAs an interesting starting point in the fight against cancer.

Against this background, the researchers led by Klusmann and Heckl wanted to know more about the role of noncoding RNAs in AML cells. For this purpose, they compiled a kind of inventory of these molecules in cancer cells taken from sick children and compared the resulting pattern with that of healthy blood stem cells. AML cells differentially expressed almost 500 noncoding RNAs in comparison to healthy cells – an indication that they could perform an important function in cancer cells. To validate this, the researchers turned off every single one of these RNA molecules by preventing the coding gene in the genome from being read. The most distinct effect they found was for the gene MYNRL15 : Cancer cells in which this gene was turned off lost their ability to replicate indefinitely and died off.

Surprisingly, however, it was not the absence of noncoding RNAs that was responsible for this effect, as Klusmann comments: “The regulatory function we observed is due to the MYNRL15 gene itself.” The team was able to show that destroying the gene altered the spatial organization of the chromatin, ie the three-dimensional structure of the genome. “This led to the deactivation of genes that AML cells need for survival,” says Klusmann. This offers a new and unforeseen possibility for fighting leukemia.

What is significant against this background is the fact that the inhibitory effect triggered by the modified MYNRL15 gene could be observed in different AML cell lines. These cells originated both from children as well as adults and included various subtypes of the disease – among them one common in people with Down syndrome. “The fact that all the leukemias we studied were dependent on this gene locus tells us it must be important,” concludes Klusmann. The researchers now hope that the cancer cells' dependence on MYNRL15 can be used to develop a specific gene therapy. “In our study, we systematically examined noncoding RNAs and their genes in AML cells for the first time, and in the process we identified a gene locus that constitutes a promising target for developing a therapy in the future,” says Klusmann, summing up.

Technical details are in the team's open access paper in iScience:

Highlights

• Long noncoding RNA locus MYNRL15 identified as a myeloid leukemia dependency
• MYNRL15 function is RNA-independent, mediated by two regulatory elements in locus
• Perturbation causes long-range looping, downregulation of cancer dependency genes
• Perturbation is anti-leukemic in primary AML cells from different genetic backgrounds

Summary

The noncoding genome presents a largely untapped source of new biological insights, including thousands of long noncoding RNA (lncRNA) loci. While lncRNA dysregulation has been reported in myeloid malignancies, their functional relevance remains to be systematically interrogated. We performed CRISPRi screens of lncRNA signatures from normal and malignant hematopoietic cells and identified MYNRL15 as a myeloid leukemia dependency. Functional dissection suggests an RNA-independent mechanism mediated by two regulatory elements embedded in the locus. Genetic perturbation of these elements triggered a long-range chromatin interaction and downregulation of leukemia dependency genes near the gained interaction sites, as well as overall suppression of cancer dependency pathways. Thus, this study describes a new noncoding myeloid leukemia vulnerability and mechanistic concept for myeloid leukemia. Importantly, MYNRL15 perturbation caused strong and selective impairment of leukemia cells of various genetic backgrounds over normal hematopoietic stem and progenitor cells in vitro, and depletion of patient-derived xenografts in vivo.

Graphical abstract

Introduction

Noncoding sequences comprise 98% of the human genome and harbor a multitude of functional units, including regulatory elements and diverse species of small and long noncoding RNA (lncRNA) loci.¹ Emerging evidence has implicated growing numbers of these noncoding units as players in a variety of physiological and disease processes, including cancer.^2,3 This represents a major opportunity for biologic and therapeutic discovery, especially for malignancies like acute myeloid leukemia (AML), whose treatment has only recently begun to evolve beyond the cytostatic regimen developed in the 1970s.⁴ Studies in AML patient cohorts have uncovered lncRNA expression signatures specific to genetic subgroups of AML^5,6,7 as well as unifying stem cell signatures.^6,8 However, due to their extensive mechanistic diversity,⁹ the study of lncRNAs can be more complicated than of other noncoding RNA species, and only a handful of lncRNA loci have undergone extensive functional characterization in AML.^10,11,12,13 Thus, despite rapid growth in the field, our knowledge of lncRNA loci and their roles in this disease remains severely limited …

Ng, Michelle; Verboon, Lonneke; Issa, Hasan; et al. Myeloid leukemia vulnerabilities embedded in long noncoding RNA locus MYNRL15 iScience 2023 26(10) DOI: 10.1016/j.isci.2023.107844

Copyright: © 2023 The authors.
Published by Elsevier Inc. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)

so, which argument are creationists going to use to explain how the cancer-causing genes was created? The one they use in their favourite false dichotomy fallacy which assumes only their god can create complex DNA, or the one which abandons that cetral creationist dogma and says somethign else can create things, namely 'Sin', that their supposedly omnipptent god is powerless over.

---

Thank you for sharing!

Tweet Link