Acadesine Circumvents Azacitidine Resistance in Myelodysplastic Syndrome and Acute Myeloid Leukemia
| العنوان: | Acadesine Circumvents Azacitidine Resistance in Myelodysplastic Syndrome and Acute Myeloid Leukemia |
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| المؤلفون: | Cluzeau, Thomas, Furstoss, Nathan, Savy, Coline, El Manaa, Wejdane, Zerhouni, Marwa, Blot, Lauriane, Calleja, Anne, Dufies, Maeva, Dubois, Alix, Ginet, Clemence, Mounier, Nicolas, Garnier, Georges, Raynaud, Sophie, Rohrlich, Pierre Simon, Peterlin, Pierre, Stamatoullas, Aspasia, Chermat, Fatiha, Fenaux, Pierre, Jacquel, Arnaud, Robert, Guillaume, Auberger, Patrick |
| المصدر: | International Journal of Molecular Sciences, Vol 21, Iss 1, p 164 (2019) International Journal of Molecular Sciences Volume 21 Issue 1 |
| بيانات النشر: | MDPI AG, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, azacitidine, Article, lcsh:Chemistry, Recurrence, Cell Line, Tumor, hemic and lymphatic diseases, Humans, Treatment Failure, neoplasms, lcsh:QH301-705.5, Aged, Cell Proliferation, Clinical Trials as Topic, apoptosis, Middle Aged, Aminoimidazole Carboxamide, phase i/ii clinical trial, Leukemia, Myeloid, Acute, stomatognathic diseases, aml, lcsh:Biology (General), lcsh:QD1-999, Drug Resistance, Neoplasm, Myelodysplastic Syndromes, mds, acadesine, Female, Ribonucleosides |
| الوصف: | Myelodysplastic syndrome (MDS) defines a group of heterogeneous hematologic malignancies that often progresses to acute myeloid leukemia (AML). The leading treatment for high-risk MDS patients is azacitidine (Aza, Vidaza® ), but a significant proportion of patients are refractory and all patients eventually relapse after an undefined time period. Therefore, new therapies for MDS are urgently needed. We present here evidence that acadesine (Aca, Acadra® ), a nucleoside analog exerts potent anti-leukemic effects in both Aza-sensitive (OCI-M2S) and resistant (OCI-M2R) MDS/AML cell lines in vitro. Aca also exerts potent anti-leukemic effect on bone marrow cells from MDS/AML patients ex-vivo. The effect of Aca on MDS/AML cell line proliferation does not rely on apoptosis induction. It is also noteworthy that Aca is efficient to kill MDS cells in a co-culture model with human medullary stromal cell lines, that mimics better the interaction occurring in the bone marrow. These initial findings led us to initiate a phase I/II clinical trial using Acadra® in 12 Aza refractory MDS/AML patients. Despite a very good response in one out 4 patients, we stopped this trial because the highest Aca dose (210 mg/kg) caused serious renal side effects in several patients. In conclusion, the side effects of high Aca doses preclude its use in patients with strong comorbidities. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::50914fe2d9447d66581df70bdf33b7c2Test https://www.mdpi.com/1422-0067/21/1/164Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....50914fe2d9447d66581df70bdf33b7c2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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