Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy.

Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy. Cell Metab. 2020 Sep 16;: Authors: Forte D, García-Fernández M, Sánchez-Aguilera A, Stavropoulou V, Fielding C, Martín-Pérez D, López JA, Costa ASH, Tronci L, Nikitopoulou E, Barber M, Gallipoli P, Marando L, Fernández de Castillejo CL, Tzankov A, Dietmann S, Cavo M, Catani L, Curti A, Vázquez J, Frezza C, Huntly BJ, Schwaller J, Méndez-Ferrer S Abstract Like normal hematopoietic stem cells, leukemic stem cells depend on their bone marrow (BM) microenvironment for survival, but the underlying mechanisms remain largely unknown. We have studied the contribution of nestin+ BM mesenchymal stem cells (BMSCs) to MLL-AF9-driven acute myeloid leukemia (AML) development and chemoresistance in vivo. Unlike bulk stroma, nestin+ BMSC numbers are not reduced in AML, but their function changes to support AML cells, at the expense of non-mutated hematopoietic stem cells (HSCs). Nestin+ cell depletion delays leukemogenesis in primary AML mice and selectively decreases AML, but not normal, cells in chimeric mice. Nestin+ BMSCs support survival and chemotherapy relapse of AML through increased oxidative phosphorylation, tricarboxylic acid (TCA) cycle activity, and glutathione (GSH)-mediated antioxidant defense. Therefore, AML cells co-opt energy sources and antioxid...
Source: Cell Metabolism - Category: Cytology Authors: Tags: Cell Metab Source Type: research

Related Links:

Patients with fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) relapsed or refractory (R/R) acute myeloid leukemia (AML) have a dismal prognosis and limited effective treatment options outside of clinical trials [1-3]. In patients with R/R AML, performing a hematopoietic stem cell transplant (HSCT) after first salvage therapy decreases the risk of relapse and improves relapse-free survival (RFS) and overall survival (OS) probabilities [4]. Traditional cytotoxic salvage chemotherapy has been largely ineffective in controlling FLT3-ITD R/R disease, enabling ≤ 20% of patients to proceed to HSCT [5,6].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
AbstractPrior studies have suggested that for leukemia patients with high-risk features, haplo-identical-hematopoietic stem cell transplantation (HID-HSCT) has a stronger anti-leukemia effect compared with HSCT using an identical sibling donor (ISD-HSCT). However, it is unclear whether an HID-HSC transplant also augments the graft-versus-leukemia (GVL) effect among refractory/relapsed (R/R) acute myeloid leukemia (AML) patients who are not in remission (NR). We conducted a retrospective analysis of 124 R/R AML patients with NR status who underwent HID-HSCT between April 2012 and December 2016 and compared these to 27 R/R A...
Source: Annals of Hematology - Category: Hematology Source Type: research
e Y Abstract Acute myeloid leukemia (AML) is a heterogeneous disease with variable presentation, molecular phenotype, and cytogenetic abnormalities and has seen very little improvement in patient survival over the last few decades. This heterogeneity supports poor prognosis partially through the variability in response to the standard chemotherapy. Further understanding of molecular heterogeneity has promoted the development of novel treatments, some of which target mitochondrial metabolism and function. This review discusses the relative dependency that AML cells have on mitochondrial function, and the ability to...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research
Genetic mutations can predict favorable or unfavorable prognosis of AML patients. Allo stem cell transplantation can provide benefits for AML patients with bad genetic mutations. AbstractTo explore the characteristics and prognostic significance of genetic mutations in acute myeloid leukemia (AML), we screened the gene mutation profile of 171 previously untreated AML patients using a next ‐generation sequencing technique targeting 127 genes with potential prognostic significance. A total of 390 genetic alterations were identified in 149 patients with a frequency of 87.1%. Younger age and high sensitivity to induction che...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
ong The first report of cancer stem cell (CSC) from Bruce et al. has demonstrated the relatively rare population of stem-like cells in acute myeloid leukemia (AML). The discovery of leukemic CSCs prompted further identification of CSCs in multiple types of solid tumor. Recently, extensive research has attempted to identity CSCs in multiple types of solid tumors in the brain, colon, head and neck, liver, and lung. Based on these studies, we hypothesize that the initiation and progression of most malignant tumors rely largely on the CSC population. Recent studies indicated that stem cell-related markers or signaling path...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Publication date: Available online 18 September 2020Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Yu-juan Xue, Yi-fei Cheng, Ai-dong Lu, Yu Wang, Ying-xi Zuo, Chen-hua Yan, Pan Suo, Le-ping Zhang, Xiao-jun Huang
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Discussion: The present study evaluated the potential prognostic role of WBC count nadir and duration of aplasia, demonstrating that they are not associated with treatment outcomes in adult patients with AML treated with intensive chemotherapy. Therefore, a short duration of aplasia seems not linked to poor therapeutic efficacy in clearing bone marrow blasts. Our findings, although needing validation in larger and more homogeneous cohorts, may offer helpful clues in the management of aplasia of AML patients.Chemotherapy
Source: Chemotherapy - Category: Cancer & Oncology Source Type: research
Conclusions: The case expands the understanding of secondary CML and emphasizes the importance of oncological vigilance in patients with secondary CML after AML therapy. PMID: 32936052 [PubMed - as supplied by publisher]
Source: Current Medical Research and Opinion - Category: Research Tags: Curr Med Res Opin Source Type: research
The treatment option for children with intermediate-risk acute myeloid leukemia (IR-AML) in first complete remission is controversial. We retrospectively analyzed the outcomes of 80 children with IR-AML, and compared the effect of chemotherapy with haplo-HSCT as post-remission treatment. Compared with chemotherapy group, haplo-HSCT group had a significantly lower risk of relapse, especially in patients with minimal residual disease ≥10-3 after induction therapy.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Original Study Source Type: research
AML is characterized by uncontrolled proliferation of clonal hematopoietic precursor cells. This interrupts normal hematopoiesis and may lead to bone marrow failure. It predominantly occurs in older adults, with the average age at diagnosis being 68 years (1). Intensive chemotherapy combined with hematopoietic stem cell (HSC) transplantation has considerably improved outcomes in younger adults. However about 80% of older adults still succumb to the disease or to the associated therapeutic toxicity (2).
Source: Experimental Hematology - Category: Hematology Authors: Tags: Review Source Type: research
More News: Acute Leukemia | Acute Myeloid Leukemia | Antidoxidants | Chemotherapy | Cytology | Leukemia | Nutrition | Stem Cell Therapy | Stem Cells