Wednesday, May 1, 2013


As we move forward, and with the increase of therapeutic agents available in our armamentarium, the focus of therapy in bone marrow failure syndrome will be on the gene altered rather then putting these disease in a global group.  Indeed a Myelodysplastic Syndrome driven by alteration of gene repair mechanisms (BRCA or RAD51) should not be treated as a Ribosomal derangement or a change in a gene that induce morphogenic changes (Dyskeratosis Congenita).  We know by now that PARP inhibitors have a better chances theoritically to act BRCA alterations then immunomodulators (Thalidomid, Revlimid) which should be attempted in Dyskeratosis like syndrome.
We know now that marrow failure syndromes particularly the congenital one have failure or gene alterations in the following targets:

1. Co-factors to DNA repair genes (Fanconi Anemia) (PARP inhibitor)
2. Telomere biology (may be the MTOR inhibitor)
3. Morphogenesis  (Revlimid, Thalidomid, Anti MEK)
4. Receptors of growth factors (Erythropoietin, thrombopoietin ) (MPL gene) (Interferon)
5. Ribosomal biogenesis (antibiotics)
6. Histone  (Acetyl transferaseinhibitor)
7. Mitochondrial Gene (MTOR Inhibitor)

Proof of concept is still needed in some cases
but that this is the way to go, we need more discernment
MDS, first obtain gene altered and make a therapeutic decision!
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