The Combination of Cudc-907 and Gilteritinib Shows Promising In Vitro and In Vivo Antileukemic Activity against FLT3-Itd AML

Investigators showed that gilteritinib and CUDC-907, a dual inhibitor of PI3K and histone deacetylases, synergistically induced apoptosis in FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) cell lines and primary patient samples and had striking in vivo efficacy.
[Blood Cancer Journal]
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CD52 Is a Novel Target for the Treatment of FLT3-ITD-Mutated Myeloid Leukemia

To explore alternative therapeutics to internal tandem duplication (ITD) of FMS-like tyrosine kinase 3 (FLT3), researchers established a cellular model of monoallelic FLT3ITD/WT cells using the CRISPR-Cas9 system in a human myeloid leukemia cell line.
[Cell Death Discovery]
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FLT3 Tyrosine Kinase Inhibitors Synergize with BCL-2 Inhibition to Eliminate FLT3/ITD Acute Leukemia Cells through BIM Activation

Scientists investigated the combination of FLT3 tyrosine kinase inhibitors (TKIs) with other drugs, and found that the combination of a FLT3 TKI and a BCL-2i synergistically reduced cell proliferation and enhanced apoptosis/cell death in FLT3/ITD cell lines and primary acute myeloid leukemia samples.
[Signal Transduction and Targeted Therapy]
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A Phase I/II Study of the Combination of Quizartinib with Azacitidine or Low-Dose Cytarabine for the Treatment of Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

In an open-label Phase I/II trial, patients of any age receiving first-salvage treatment for FLT3-ITD acute myeloid leukemia (AML) or age >60 years with untreated myelodysplastic syndrome or AML were treated with quizartinib plus azacitidine or low-dose cytarabine.
[Haematologica]
Swaminathan, M., Kantarjian, H. M., Levis, M., Guerra, V., Borthakur, G., Alvarado, Y., DiNardo, C. D., Kadia, T., Garcia-Manero, G., Ohanian, M., Daver, N., Konopleva, M., Pemmaraju, N., Ferrajoli, A., Andreeff, M., Jain, N., Estrov, Z., Jabbour, E. J., Wierda, W. G., … Cortes, J. E. (2020). A phase I/II study of the combination of quizartinib with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia and myelodysplastic syndrome. Haematologica. https://doi.org/10.3324/haematol.2020.263392 Cite
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Clinical Significance of RAS Pathway Alterations in Pediatric Acute Myeloid Leukemia

Scientists analyzed the frequency, clinical significance, and prognostic relevance of RAS pathway alterations in 328 pediatric patients with de novo acute myeloid leukemia.
[Haematologica]
Kaburagi, T., Yamato, G., Shiba, N., Yoshida, K., Hara, Y., Tabuchi, K., Shiraishi, Y., Ohki, K., Sotomatsu, M., Arakawa, H., Matsuo, H., Shimada, A., Taki, T., Kiyokawa, N., Tomizawa, D., Horibe, K., Miyano, S., Taga, T., Adachi, S., … Hayashi, Y. (2020). Clinical significance of RAS pathway alterations in pediatric acute myeloid leukemia. Haematologica. https://doi.org/10.3324/haematol.2020.269431 Cite
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OTS167 Blocks FLT3 Translation and Synergizes with FLT3 Inhibitors in FLT3 Mutant Acute Myeloid Leukemia

OTS167 alone or in combination with tyrosine kinase inhibitors were used to investigate the effect of OTS167 on FLT3 signaling and expression in human Fms-like tyrosine kinase 3 (FLT3) mutant acute myeloid leukemia cell lines and primary cells.
[Blood Cancer Journal]
Eisfelder, B. J., Saygin, C., Wynne, J., Colton, M. W., Fischietti, M., Beauchamp, E. M., Cheng, J. X., Odenike, O., Roboz, G., Alachkar, H., & Stock, W. (2021). OTS167 blocks FLT3 translation and synergizes with FLT3 inhibitors in FLT3 mutant acute myeloid leukemia. Blood Cancer Journal, 11(3), 1–15. https://doi.org/10.1038/s41408-021-00433-3 Cite
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Antileukemic Activity of the VPS34-IN1 Inhibitor in Acute Myeloid Leukemia

Using a recently developed specific inhibitor, the authors found that vacuolar protein sorting 34 inhibition induces apoptosis in acute myeloid leukemia cells but not in normal CD34+ hematopoietic cells.
[Oncogenesis]
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Preclinical Evaluation of a Regimen Combining Chidamide and ABT-199 in Acute Myeloid Leukemia

Scientists reported that a newly emerged histone deacetylase inhibitor, chidamide, at low-cytotoxicity dose enhanced the anti-AML activity of ABT-199, while sparing normal hematopoietic progenitor cells.
[Cell Death & Disease]
Chen, K., Yang, Q., Zha, J., Deng, M., Zhou, Y., Fu, G., Bi, S., Feng, L., Xu-Monette, Z. Y., Chen, X. L., Fu, G., Dai, Y., Young, K. H., & Xu, B. (2020). Preclinical evaluation of a regimen combining chidamide and ABT-199 in acute myeloid leukemia. Cell Death & Disease, 11(9), 1–13. https://doi.org/10.1038/s41419-020-02972-2 Cite
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All-Trans Retinoic Acid in Non-Promyelocytic Acute Myeloid Leukemia: Driver Lesion Dependent Effects on Leukemic Stem Cells

The author summarizes the role of all-trans retinoic acidin normal hematopoiesis and in cute amyeloid leukemia (AML), focusing on its impact on AML stem cells.
[Cell Cycle]
Nguyen, C. H., Grandits, A. M., Purton, L. E., Sill, H., & Wieser, R. (2020). All-trans retinoic acid in non-promyelocytic acute myeloid leukemia: driver lesion dependent effects on leukemic stem cells. Cell Cycle, 0(0), 1–16. https://doi.org/10.1080/15384101.2020.1810402 Cite
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All-Trans Retinoic Acid in Non-Promyelocytic Acute Myeloid Leukemia: Driver Lesion Dependent Effects on Leukemic Stem Cells

This authors summarize the role of all-trans retinoic acid in normal hematopoiesis and in acute myeloid leukemia (AML), focusing on its impact on AML stem cells.
[Cell Cycle]
Nguyen, C. H., Grandits, A. M., Purton, L. E., Sill, H., & Wieser, R. (2020). All-trans retinoic acid in non-promyelocytic acute myeloid leukemia: driver lesion dependent effects on leukemic stem cells. Cell Cycle, 0(0), 1–16. https://doi.org/10.1080/15384101.2020.1810402 Cite
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Characterization of FLT3-ITDmut Acute Myeloid Leukemia: Molecular Profiling of Leukemic Precursor Cells

Investigators characterized the distribution of FLT3-ITD mutation in different progenitor cell subsets to shed light on the subclonal architecture of FLT3-ITDmut acute myeloid leukemia.
[Blood Cancer Journal]
Travaglini, S., Angelini, D. F., Alfonso, V., Guerrera, G., Lavorgna, S., Divona, M., Nardozza, A. M., Consalvo, M. I., Fabiani, E., De Bardi, M., Neri, B., Forghieri, F., Marchesi, F., Paterno, G., Cerretti, R., Barragan, E., Fiori, V., Dominici, S., Del Principe, M. I., … Ottone, T. (2020). Characterization of FLT3 -ITD mut acute myeloid leukemia: molecular profiling of leukemic precursor cells. Blood Cancer Journal, 10(8), 1–11. https://doi.org/10.1038/s41408-020-00352-9 Cite
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