Evolving therapy of adult acute lymphoblastic leukemia: state-of-the-art treatment and future directions

Samra, Bachar; Jabbour, Elias; Ravandi, Farhad; Kantarjian, Hagop M.

doi:10.1186/s13045-020-00905-2

Cited by 122 publications

(91 citation statements)

References 166 publications

(207 reference statements)

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“…Novel therapeutics, have been introduced in the standard treatment regimens based on multiagent chemotherapies. TKIs which target dysregulated signaling pathways have given promising results with improved overall survival ( 97 ). Immune cells can also be addressed to leukemic cells through the use of monoclonal antibodies targeting surface receptors.…”

Section: Treatments Targeting the Leukemic Nichementioning

confidence: 99%

Toward Therapeutic Targeting of Bone Marrow Leukemic Niche Protective Signals in B-Cell Acute Lymphoblastic Leukemia

et al. 2021

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B-cell acute lymphoblastic leukemia (B-ALL) represents the malignant counterpart of bone marrow (BM) differentiating B cells and occurs most frequently in children. While new combinations of chemotherapeutic agents have dramatically improved the prognosis for young patients, disease outcome remains poor after relapse or in adult patients. This is likely due to heterogeneity of B-ALL response to treatment which relies not only on intrinsic properties of leukemic cells, but also on extrinsic protective cues transmitted by the tumor cell microenvironment. Alternatively, leukemic cells have the capacity to shape their microenvironment towards their needs. Most knowledge on the role of protective niches has emerged from the identification of mesenchymal and endothelial cells controlling hematopoietic stem cell self-renewal or B cell differentiation. In this review, we discuss the current knowledge about B-ALL protective niches and the development of therapies targeting the crosstalk between leukemic cells and their microenvironment.

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Section: Treatments Targeting the Leukemic Nichementioning

confidence: 99%

Toward Therapeutic Targeting of Bone Marrow Leukemic Niche Protective Signals in B-Cell Acute Lymphoblastic Leukemia

et al. 2021

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“…ALL is characterized by the proliferation of a huge number of immature lymphocytes in different tissues. R/R ALL patients used to have poor clinical outcomes even after heavy salvage chemotherapy and hematopoietic stem cell transplantation (HSCT) [ 36 , 37 ]. However, in recent years, new targeted drugs have been developed as remedies for ALL.…”

Section: Mechanisms Of Bite Actionmentioning

confidence: 99%

Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies

et al. 2021

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Harnessing the power of immune cells, especially T cells, to enhance anti-tumor activities has become a promising strategy in clinical management of hematologic malignancies. The emerging bispecific antibodies (BsAbs), which recruit T cells to tumor cells, exemplified by bispecific T cell engagers (BiTEs), have facilitated the development of tumor immunotherapy. Here we discussed the advances and challenges in BiTE therapy developed for the treatment of hematologic malignancies. Blinatumomab, the first BiTE approved for the treatment of acute lymphocytic leukemia (ALL), is appreciated for its high efficacy and safety. Recent studies have focused on improving the efficacy of BiTEs by optimizing treatment regimens and refining the molecular structures of BiTEs. A considerable number of bispecific T cell-recruiting antibodies which are potentially effective in hematologic malignancies have been derived from BiTEs. The elucidation of mechanisms of BiTE action and neonatal techniques used for the construction of BsAbs can improve the treatment of hematological malignancies. This review summarized the features of bispecific T cell-recruiting antibodies for the treatment of hematologic malignancies with special focus on preclinical experiments and clinical studies.

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“…60's to a particularly bleak 10% [12]. In ALL, recent advances for example in the use of tyrosine kinase inhibitors and CAR-T cell therapy, have started to suggest improvements to overall survival [10]. However, in patients fit enough to tolerate chemotherapy, the standard treatment for AML since 1973 has been a seven-day continuous intravenous infusion of cytarabine (Ara-C) (100-200 mg/m 2 ) and 3 daily doses of daunorubicin (45-90 mg/m 2 ), sometimes followed by allogeneic or autologous stem cell transplantation, and despite some recent advances (reviewed in [13,14]), current treatments appear to have reached their efficacious limits and new therapies are required.…”

Section: Human Hematopoiesis Schematic Diagram Showing Classical Model Of Hematopoietic Lineage Commitment With Phenotypical Cell Surfacementioning

confidence: 99%

“…They occur due to one or more genetic insults. Whilst ALL is predominantly a disease of children (80%), with a greater than 90% 5 y survival rate [10], in adults long term survival stands at only 30-40% [11]. AML in contrast is primarily a disease of the elderly, and like adult ALL it's 5 y survival rate is around 30%, however this falls in the over…”

Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species and Metabolic Re-Wiring in Acute Leukemias

Robinson¹,

Darley²,

Tonks³

2021

Acute Leukemias

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Reactive oxygen species (ROS) is the collective term for several oxygen containing free radicals, such as hydrogen peroxide. ROS is important in innate immunity, protein folding in the endoplasmic reticulum and as a cell signalling molecule involved in cellular proliferation, survival, differentiation, and gene expression. ROS has been implicated in both hematopoietic stem cell quiescence and hematopoietic differentiation. Consequently, ROS is of considerable interest as a therapeutic target, with both pro-oxidant and anti-oxidant cellular modulation being explored. Recently, it has been established that increased ROS production in acute myeloid leukemia (AML) leads to increased glycolysis and metabolic reprogramming. It is often stated as a key tenet of the Warburg effect, that transformed cells, including AML, show increased aerobic glycolysis accompanied by increased cellular glucose uptake and lactate secretion. This review will summarize ROS state of the art in acute leukemia and how these reactive molecules re-wire metabolism in cancer cells. The review will focus on what are ROS? What are the sources of ROS in hematopoietic cells and their function and how this relates to the Warburg effect and regulation of metabolic pathways in acute leukemias.

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Evolving therapy of adult acute lymphoblastic leukemia: state-of-the-art treatment and future directions

Cited by 122 publications

References 166 publications

Toward Therapeutic Targeting of Bone Marrow Leukemic Niche Protective Signals in B-Cell Acute Lymphoblastic Leukemia

Toward Therapeutic Targeting of Bone Marrow Leukemic Niche Protective Signals in B-Cell Acute Lymphoblastic Leukemia

Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies

Reactive Oxygen Species and Metabolic Re-Wiring in Acute Leukemias

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