New insights into leukemic microenvironment in bone marrow

by Alexey Bersenev on January 18, 2009 · 2 comments

in Journal club, leukemia, niche

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We have had a journal club this week. I picked and presented a paper – Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells by Angela Colmone from Dorothy Sipkins group (U of Chicago).
I decided to make my presentation public. I used one of the tools allows me upload and share presentations online – SlideShare.net.
Please welcome to comment!

{ 2 comments… read them below or add one }

JWS January 18, 2009 at 9:18 pm

In my opinion, the paper addresses a new insight about ‘leukemic niche’ and if the niche can be modulated therapeutically by neutralizing antibodies against Stem Cell Factor. While the concept is new, there is a concern that the paper is somewhat ‘rushed’ based on the quality of scientific investigations:

1. It is not clear whether CD34+ cells ‘migrate’ into leukemic Nalm-6 positive niches. First, CD34+ does not actually home close to Nalm-6+ cells within 1~3 hours of transplantation. The authors claim that CD34+ cells are then ‘migrate’ towards Nalm-6+ cells after 7 days of homing. It is not clear if it is CD34+ cell that moves to Nalm-6+ cells or there has been an alteration in Nalm-6+ cells in terms of their numbers or their distributions within BM – therefore it is not clear if CD34+ preferentially ‘migrate’ to Nalm-6+ cells as presented by the paper.

2. It is not clear if CD34+ cells that interact with Nalm-6+ cells acquire leukemic properties – it may be the authors think that CD34+ are just normal stem cells and Nalm-6+ niche cells are just able to attract CD34+ more, preventing mobilization of CD34+ cells. However, this could be quite opposite – CD34+ cells may be altered by Nalm-6+ environment. This has an important therapeutic implication – just because neutraling antibody against SCF can restore CD34+ mobilization doesn’t really mean it has a therapeutic implication because there is a possibility that CD34+ cells could be altered by the time they interact with leukemic niches. To me, this is an important question and has to be addressed before the publication in Science.

Generally, the paper could be done better.

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Alex January 18, 2009 at 11:09 pm

to JWS –
I’d agree with 1.
According point 2. Authors claim was that CD34+ altered by leukemic microenvironment, because they express abnormal behavior.
I agree with your point – why do we need to restore mobilization of abnormal HSC?

Another unclear thing for me that I didn’t get why they showed zero expression of SCF in steady-state BM? It’s should be there, alittle but some background. If you remember this Weissman paper showed that anti-cKit (receptor for SCF) antibody can remove 98% of HSC. So I think treatment of anti-SCF antibody can remove some normal host HSC or niche cells (such as MSC) mobilize them.

I think this paper got Science because of topic so hot and unknown. But experiments could be done more accurate I think.

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