CLL cells accumulate genetic aberrations prior to the first therapy even in outwardly inactive disease phase

[Jm954]

No definite conclusions from this paper about genetic evolution and disease drivers but interesting.

"Most CLL cases are diagnosed during the inactive disease phase. Clonal evolution is considered a key factor in CLL progression and relapse after treatment. A large number of frequently mutated genes have been identified and several putative driver mutations likely to confer selective growth advantage to CLL tumour cells have been proposed.

Clonal shifts can occur and have been identified using paired treatment-naïve and relapsed CLL samples. This is due to the expansion of pre-existing subclones under therapeutic pressure, demonstrating that clonal evolution may lead to CLL relapse.

Understanding CLL evolution from the time of diagnosis to therapy need may be essential to gain insight into the process of transformation from the initial inactive form to later more aggressive stages."

nature.com/articles/s41375-...

Jackie

[seelel]

This is an interesting paper. The ground it covers has been covered before, but it builds on previous known ideas.

The one factor that is not included which I think aught to be included, is the factor of the internal climate of the body and its ability to promote or suppress clonal evolution. I hope that the subject will one day encompass the bigger picture of the 'state' of the body.

[Jm954 Administrator in reply to seelel]

Hi, are you referring to the impact of lifestyle/epigenetics or simple fitness scoring systems? I'm sure you're right but how would we be able to consistently and rigorously measure past 'states' of the body which will have had an influence?

Jackie

[seelel in reply to Jm954]

I guess I'm thinking about lifestyle factors that can be avoided that mess with the body's ability to do good housekeeping. Past and present. The information provided to the general public about what constitutes a healthy lifestyle currently skims the surface of a fairly stagnant pond.

[LeoPa in reply to Jm954]

I guess there is no need to rigorously study, compare etc. The easiest way is to try and see if the changes work for us. We are all different and might react to the same lifestyle interventions differently even. Therefore everybody is on his own. Waiting for a universally approved sure fire lifestyle change proven by trials and found beneficial for everybody might never come around. A bit of a well intended lifestyle change should not be too dangerous unless one goes the "30 bananas a day" route or something similarly crazy😁. Yes, there's a website named like that.

[Smakwater]

You find all the Good books Jackie,

A cancer Genome interpreter that distinguishes passengers from drivers, (somebody stayed up late).

I pulled this from the publication, as it seemed to jumped off the page while I was reading.

"We conclude that the acquisition of aberrations is not limited to the active disease phase or relapses after therapy [3, 5, 6]. Moreover, mutational profiles of indolent or outwardly stable CLL cases show that the presence of CLL clones bearing driver mutations do not have to correspond directly with disease progression. Therefore, simple mutation acquisition does not necessarily lead to immediate disease progression; nevertheless, accumulating changes precede the manifestation of disease activity. In addition, clonal evolution can occur in the absence of adverse prognostic factors such as the presence of high-risk cytogenetic alterations or unmutated IGHV. In fact, the acquisition of mutations can happen in the absence of any FISH alterations (P35 or P45) as well as in IGHV-mutated CLLs (P46). Unfortunately, analysis of genomic changes does not fully explain the transformation to a more aggressive stage in all CLL patients (P40)."

So much for Probability Analytics?

JM

[Jm954 Administrator in reply to Smakwater]

Exactly! CLL still keeps us guessing and out manoeuvring us 🤔

[Smakwater in reply to Jm954]

A stolen line from Jackie Gleason,

One of These days Alice, Bang, Zoom, CLL to the Moon!

[Psalm22-3]

So is the upshot that W&W may increase risks of incubating a more adaptive disease and thus adverse longer-term outcomes? That is, one should attack before the enemy has a chance to build up a diversified arsenal?

[guzzifan in reply to Psalm22-3]

What you're saying would seem a logical conclusion, except that it conflicts with the supposed practical experience that W&W is based on. The conventional opinion is that there is no clinical disadvantage, and some advantages, to W&W. I wonder what formal research W&W is based on? It certainly seems to be followed by all the best CLL specialists.