This type of synergistically acting combinations may represent prototypes for novelantileukemic therapy.
Aviram Trachtenberg, Suchismita Muduli, Katarzyna Sidoryk, Marcin Cybulski, MichaelDanilenko 2019, 'Synergistic Cytotoxicity of Methyl 4-Hydroxycinnamate and Carnosic Acid to Acute MyeloidLeukemia Cells via Calcium-Dependent Apoptosis Induction', Frontiers in Pharmacologyhttps://www.frontiersin.org/article/10.3389/fphar.2019.00507/full. Retrieved from DOAJ CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
In addition, further perturbations in immune function are related to the antileukemic therapies.
Piotr Stelmach, Tadeusz Robak 2013, 'Pathogenesis, prophylaxis and treatment of infections in patients with chronic lymphocyticleukemia ', Postępy Higieny i Medycyny Doświadczalnejhttp://journals.indexcopernicus.com/fulltxt.php?ICID=1053901. Retrieved from DOAJ CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
Combination therapy with asparaginase and dexamethasone demonstrated synergistic antileukemic effects across all six xenografts studied.
Seth E Karol, Laura J Janke, John C Panetta, Laura B Ramsey, Xiangjun Cai, MoniqueA Payton, David A Jenkins, William E Evans, Mary V Relling 2019, 'Asparaginase combined with discontinuous dexamethasone improves antileukemic efficacywithout increasing osteonecrosis in preclinical models.', PLoS ONEhttp://europepmc.org/articles/PMC6502315?pdf=render. Retrieved from PLOS CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
Moreover, the novel formulation retained tigecycline's antileukemic activity in vivo.
Yulia Jitkova, Marcela Gronda, Rose Hurren, Xiaoming Wang, Carolyn A Goard, BozhenaJhas, Aaron D Schimmer 2014, 'A novel formulation of tigecycline has enhanced stability and sustained antibacterialand antileukemic activity.', PLoS ONEhttp://europepmc.org/articles/PMC4037176?pdf=render. Retrieved from PLOS CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
Eleven of the 29 point mutants increased, whereas four decreased antileukemic activity.
Yan-shan Ji, Betty H. Johnson, M. Scott Webb, Brad Thompson 2002, 'Mutational Analysis of DBD*-a Unique Antileukemic Gene Sequence', Neoplasia: An International Journal for Oncology Researchhttp://www.sciencedirect.com/science/article/pii/S1476558602800379. Retrieved from DOAJ CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
Ongoing studies are elucidating the molecular mechanisms underlying its antileukemic activity.
M. R. Ricciardi, R. Licchetta, S. Mirabilii, M. Scarpari, A. Parroni, A. A. Fabbri,P. Cescutti, M. Reverberi, C. Fanelli, A. Tafuri 2017, 'Preclinical Antileukemia Activity of Tramesan: A Newly Identified Bioactive FungalMetabolite', Oxidative Medicine and Cellular Longevityhttp://dx.doi.org/10.1155/2017/5061639. Retrieved from DOAJ CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
This implies that biomarkers of response need to accompany the development of antileukemic therapies for sharply defined patient subgroups.
Vibeke Andresen, Bjørn T. Gjertsen, Bjørn T. Gjertsen 2017, 'Drug Repurposing for the Treatment of Acute Myeloid Leukemia', Frontiers in Medicinehttp://journal.frontiersin.org/article/10.3389/fmed.2017.00211/full. Retrieved from DOAJ CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)
Finally, the presence of clonal heterogeneity was associated with adverse prognosis for patients receiving intensive antileukemic treatment.
Ina Nepstad, Kimberley Joanne Hatfield, Tor Henrik Anderson Tvedt, Håkon Reikvam,Øystein Bruserud 2018, 'Clonal Heterogeneity Reflected by PI3K-AKT-mTOR Signaling in Human Acute Myeloid LeukemiaCells and Its Association with Adverse Prognosis', Cancershttp://www.mdpi.com/2072-6694/10/9/332. Retrieved from DOAJ CC BY 4.0 (https://creativecommons.org/licenses/by-sa/4.0/legalcode)