Developing new drugs for adult T-cell leukemia/lymphoma by targeting hypoxia: insights from toxicity of MS-275 and its analogs.

The low survival rate of adult T-cell leukemia/lymphoma (ATL) underscores the critical need for innovative therapeutic agents. While the pharmacokinetics of HDACis have been documented in several hematological neoplasms, there is a notable gap in research regarding their activity against ATL. Given that hypoxia can induce unpredictable effects on lymphoma cells, this study aimed to evaluate the toxic effects of MS-275 and novel analogs on ATL cells in hypoxic condition for the first time.

DNMT3A-R882: a mutation with many paradoxes.

Understanding the underlying mechanism of acute myeloid leukemia (AML) has led to the discovery of novel biomarkers to help predict, treat and monitor leukemia. DNA (cytosine-5)-methyltransferase 3 A (DNMT3A) is considered a prognostic and therapeutic epigenetic target in AML patients with a hotspot mutation of R882. R882 mutation is associated with impaired differentiation of Hematopoietic stem cells in the bone marrow and disease progression.

Comparing toxicity of galbanic acid, auraptene and umbelliprenin on adult T-cell leukaemia-lymphoma in normoxia and hypoxia.

Natural coumarins are valuable agents that induce anticancer effects and/or enhance sensitivity to therapeutic modalities. Galbanic acid (GBA), auraptene (AUR) and umbelliprenin (UMB) are coumarins derived from Ferula species with various pharmaceutical activities. The aim of the current research was to compare toxic effects of GBA, AUR, and UMB on human lymphoma cells in normoxia and hypoxia.

Radiation Response of Human Leukemia/Lymphoma Cells was Improved by 7-Geranyloxycoumarin.

Objectives: Adult T-cell leukemia/lymphoma (ATLL) is a blood neoplasm with specific geographic distribution. Although radiotherapy is a palliative treatment that provides long-term local control, single use of radiation leads to complications for patients. To introduce a novel multimodal approach against ATLL, we investigated combinatorial effects of 7-geranyloxycoumarin and radiation in vitro.

Galbanic Acid Improves Accumulation and Toxicity of Arsenic Trioxide in MT-2 Cells.

Background: Galbanic acid (GBA) is a sesquiterpene coumarin with valuable pharmacological effects. Adult T-cell lymphoma (ATL) is an aggressive lymphoid malignancy with a low survival rate. Although arsenic trioxide (ATO) is a standard therapeutic agent for ATL treatment, the efficacy of chemotherapy is limited due to the chemoresistance of cells.

The Emerging Roles of Aldehyde Dehydrogenase in Acute Myeloid Leukemia and Its Therapeutic Potential.

Acute myeloid leukemia (AML) is a malignant disorder characterized by myeloid differentiation arrest and uncontrolled clonal expansion of abnormal myeloid progenitor cells. AML is the most common malignant bone marrow (BM) disease in adults and accounts for approximately 80% of adult leukemia cases. There has been little improvement in the treatment of patients with AML over the past decade.

Prognostic significance of ATM mutations in chronic lymphocytic leukemia: A meta-analysis.

Background: The ATM protein acts as an essential part of the signal transduction pathway upstream of p53 which activates following induction of DNA double-strand breaks (DSBs) and leads to transcriptional proapoptotic genes activation that synchronizes DNA repair.

Aim: Several studies have assessed the relationship between ATM mutations and the clinical prognosis in patients with chronic lymphocytic leukemia (CLL). However, its prognostic value has not yet been fully clarified.