10 Sep
10:03

This is a new article about an amazing study that gives great hope for fighting against leukemia. Actually this new treatment targets most particularly chronic myelogenous leukemia. And I am proud to announce that this discovery was made by French researchers, from the CEA (Atomic energy and alternatives energies commission).

First of all, what is leukemia? It is a special type of cancer, which involves blood cells. This disease begins in bone marrow. Leukemia cells do not act normally because they have a lot of mutations in their DNA. Stems cells that are in bone marrow produce red blood cells, white blood cells and platelets.

Illu_blood_cell_lineage
A patient who has leukemia produces a lot of abnormal white blood cells and these cells invade bone marrow, and finally blood itself. Then the patient suffers from bone marrow failure because he is not able to produce the sufficient amount of normal white blood cells. This can lead to anemia or other side effects.

Chronic myelogenous leukemia is linked to a characteristic chromosomal translocation called the Philadelphia chromosome. This corresponds to a genetic exchange of information between chromosomes 9 and 22 leading to a fusion between genes ABL and BRC. This mutation creates an abnormal ABL gene. But what does really happen? Actually, a part of the chromosomes 9 and 22 will disrupt and take eachother’s place. ABL is known to be an oncogenic gene. It means that when this gene is expressed it can lead to tumors formation. Nowadays, sequencing and isolation of this mutation is used to confirm a diagnosis of chronic myelogenous leukemia. After being transcripted into RNA, this fusion gene will then be translated into a special protein. This protein is a tyrosin-kinase type of protein, this is not changed compared to the normal protein, but its activity is much higher! A tyrosine kinase will perform a phosphorylation on a tyrosin residue. Tyrosin is a type of amino acid (see the formula below).

Tyrosine

This abnormal protein interacts with an interleukin receptor: IL-3 making this receptor constitutively active! The interleukin receptor is not regulated anymore. This is a huge issue because in healthy cells, tyrosine kinase receptors are turned off when needed. As IL-3 is always active, it activates a lot of proteins involved in cell cycle. This make the cell cycle going faster, cells can then divide and proliferate faster! But if you increase the production of cells that have a problem in their DNA, then you propagate the mutation. Moreover, the mutated gene inhibits DNA repair leading to a very unstable genome.

1000px-Philadelphia_ChromosomF1.large

The usual way to treat this disease is a drug called Imatinib, this is a tyrosin kinase inhibitor. This drug was found by Novartis®. The problem is that Imatinib is very expensive 2500 euros for a 30 tablets box. This encourages researchers to look for another molecule to treat chronic myelogenous leukemia. As you can see on this pathway, when you have philadelipha mutation, your cells have a tendency to survive and to proliferate, whereas when you add Imatinib or other derivatives, it blocks cell surviving preventing the disease to arise. Unfortunately less than 10% of patients reach a level of healing where cancerous stem cells cannot be detected anymore. This means that when the treatment is stopped, the cancer can appear another time.

864px-Mechanism_imatinib400px-Imatinib_mesylate

Now that we know what is the disease, I would like to tell you about the new discovery made by these French researchers. This new treatment targets stem cells that lead to the disease. Patients who were given this treatment show no signs of the disease 5 years after having stopped the treatment. These researchers have shown that the pool of residual cancerous stem cells can be targeted by another type of drug: glitazones. These drugs are known as antidiabetics. They are agonist of peroxisome proliferator-activated receptor γ (PPAR-γ). This study shows that activation of PPAR- γ mediated by glitazones dicrease the level of a protein called STAT5 (signal transducer and activator of transcription 5). This protein is involved in a signaling cascade, which increase the expression of HIF2a (hypoxia inducible factor 2a) and CITED2 (Cbp/p300-interacting transactivator 2). These two proteins have a very important role: they maintain stemness and quiescence. Quiescent cells are cells that will not be active, they will not proliferate and they will not differentiate until they leave this state of quiescence.

When glitazones where given to patients who were before treated with Imatinib, residual stem cells were maintained quiescent and then purged from the bone marrow. As a result, no cancerous cells could be detected 5 years after having stopped the treatment with glitazones. This may be the first step towards the complete eradication of this type of cancer!

Here is the end of this article. I hope you liked this news and the hopes it gives. Bye bye!

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« What is happening when you enter a black hole? The new theory of Stephen Hawking! »

Billythekid

PhD Student in Biophysics

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2 Comments

    Cassie

    11 September 2015 at 10 h 03 min

    Hey there this is somewhat of off topic but I was wondering if blogs
    use WYSIWYG editors or if you have to manually code with
    HTML. I’m starting a blog soon but have no coding knowledge so I wanted to get advice from someone with experience.
    Any help would be enormously appreciated!

      Billythekid

      11 September 2015 at 10 h 03 min

      Hi, I can answer this question even if it is a bit out of the subject. I used a WordPress template where I added a bit of code (HTML, CSS) to modify what I wanted. But with WordPress you can have a pretty nice WYSIWYG editor. You can start a blog with this editor, it is really easy and user friendly. I hope you will reach your goal.
      Bye!

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