Anti-leukemic effects of all-trans retinoic acid in combination with Daratumumab in acute myeloid leukemia

Buteyn, Nathaniel J; Fatehchand, Kavin; Santhanam, Ramasamy; Fang, Huiqing; Dettorre, Gino M; Gautam, Shalini; Harrington, Bonnie K.; Henderson, Sally E.; Merchand-Reyes, Giovanna; Mo, Xiaokui; Benson, Don M.; Carson, William E.; Vasu, Sumithira; Byrd, John C.; Butchar, Jonathan P.; Tridandapani, Susheela

doi:10.1093/intimm/dxy040

Cited by 22 publications

(20 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, a combined effect of ATRA and bromodomain inhibitor JQ1 has been demonstrated on non-APL AML cells with a synergistic growth inhibition resulting from differentiation or apoptosis [ 30 ]. Similarly, inhibition of the SUMO pathway appeared as a promising strategy to sensitize patients with non-APL AML to retinoids [ 31 ], and the combination of ATRA with the anti-CD38 daratumumab to increase cytotoxicity among AML blasts in vitro and overall survival in murine engraftment models of AML [ 32 ]. Preliminary studies have suggested that the epigenetic and transcriptional state of leukemia cells determines their susceptibility to ATRA [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of All-Trans-Retinoic Acid in High-Risk Acute Myeloid Leukemia with Overexpression of EVI1

et al. 2019

View full text Add to dashboard Cite

Introduction: EVI1 (MECOM)-positive acute myeloid leukemia (AML) cells have shown in vitro sensitivity to all-trans-retinoic acid (ATRA) by inducing differentiation, cell death, and decreased leukemic engraftment. Methods: In this pilot study, we investigated the response to ATRA in 13 high-risk AML patients with overexpression of EVI1. Results: Seven of the 13 patients (53.8%) achieved complete remission (CR), and response can be combined with a decreased of the leukemia stem cell pool. Conclusion: These primary results tend to confirm in vitro results and suggest that addition of ATRA might be of benefit in the treatment of patients with EVI1-positive AML.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy of All-Trans-Retinoic Acid in High-Risk Acute Myeloid Leukemia with Overexpression of EVI1

et al. 2019

View full text Add to dashboard Cite

show abstract

“…A recent study identified that all-trans retinoic acid (ATRA) increases CD38 expression on acute myeloid leukemia (34). We next identified if this was the case for multiple myeloma.…”

Section: Cd38 Inhibition Prevents Mitochondrial Transfer and Tnt Formmentioning

confidence: 97%

CD38-Driven Mitochondrial Trafficking Promotes Bioenergetic Plasticity in Multiple Myeloma

et al. 2019

View full text Add to dashboard Cite

Metabolic adjustments are necessary for the initiation, proliferation, and spread of cancer cells. Although mitochondria have been shown to move to cancer cells from their microenvironment, the metabolic consequences of this phenomenon have yet to be fully elucidated. Here, we report that multiple myeloma cells use mitochondrial-based metabolism as well as glycolysis when located within the bone marrow microenvironment. The reliance of multiple myeloma cells on oxidative phosphorylation was caused by intercellular mitochondrial transfer to multiple myeloma cells from neighboring nonmalignant bone marrow stromal cells. This mitochondrial transfer occurred through tumor-derived tunneling nanotubes (TNT).Moreover, shRNA-mediated knockdown of CD38 inhibits mitochondrial transfer and TNT formation in vitro and blocks mitochondrial transfer and improves animal survival in vivo. This study describes a potential treatment strategy to inhibit mitochondrial transfer for clinical benefit and scientifically expands the understanding of the functional effects of mitochondrial transfer on tumor metabolism.Significance: Multiple myeloma relies on both oxidative phosphorylation and glycolysis following acquisition of mitochondria from its bone marrow microenvironment.

show abstract

“…Acute myeloid leukemia (AML) is another disease where the anti-tumor effects of DARA have been investigated. In combination with all-trans retinoic acid (ATRA), DARA enhanced cytotoxicity of AML cells [ 70 ], while as a single agent, DARA induced an inhibition of mitochondrial transfer from mesenchymal stromal cells to AML cells, thus reducing the tumor burden [ 71 ]. Moreover, the efficacy of anti-CD38 therapy was assessed also in post-transplant refractory B-acute lymphoblastic leukemia [ 72 , 73 , 74 ].…”

Section: Clinical Applications Outside MMmentioning

confidence: 99%

The Circular Life of Human CD38: From Basic Science to Clinics and Back

et al. 2020

View full text Add to dashboard Cite

Monoclonal antibodies (mAbs) were initially considered as a possible “magic bullet” for in vivo elimination of tumor cells. mAbs represented the first step: however, as they were murine in nature (the earliest experience on the field), they were considered unfit for human applications. This prompted the development of techniques for cloning the variable regions of conventional murine antibodies, genetically mounted on human IgG. The last step in this years-long process was the design for the preparation of fully human reagents. The choice of the target molecule was also problematic, since cancer-specific targets are quite limited in number. To overcome this obstacle in the planning phases of antibody-mediated therapy, attention was focused on a set of normal molecules, whose quantitative distribution may balance a tissue-dependent generalized expression. The results and clinical success obtained with anti-CD20 mAbs revived interest in this type of strategy. Using multiple myeloma (MM) as a tumor model was challenging first of all because the plasma cells and their neoplastic counterpart eluded the efforts of the Workshop on Differentiation Antigens to find a target molecule exclusively expressed by these cells. For this reason, attention was turned to surface molecules which fulfill the requisites of being reasonably good targets, even if not specifically restricted to tumor cells. In 2009, we proposed CD38 as a MM target in virtue of its expression: it is absent on early hematological progenitors, has variable but generalized limited expression by normal cells, but is extremely high in plasma cells and in myeloma. Further, regulation of its expression appeared to be dependent on a variety of factors, including exposure to all-trans retinoic acid (ATRA), a potent and highly specific inducer of CD38 expression in human promyelocytic leukemia cells that are now approved for in vivo use. This review discusses the history of human CD38, from its initial characterization to its targeting in antibody-mediated therapy of human myeloma.

show abstract

Anti-leukemic effects of all-trans retinoic acid in combination with Daratumumab in acute myeloid leukemia

Cited by 22 publications

References 35 publications

Efficacy of All-Trans-Retinoic Acid in High-Risk Acute Myeloid Leukemia with Overexpression of EVI1

Efficacy of All-Trans-Retinoic Acid in High-Risk Acute Myeloid Leukemia with Overexpression of EVI1

CD38-Driven Mitochondrial Trafficking Promotes Bioenergetic Plasticity in Multiple Myeloma

The Circular Life of Human CD38: From Basic Science to Clinics and Back

Contact Info

Product

Resources

About