bims-almceb Biomed News
on Acute Leukemia Metabolism and Cell Biology
Issue of 2022‒03‒20
eight papers selected by
Camila Kehl Dias
Federal University of Rio Grande do Sul
  1. Paper of April Issue of Stem Cell Reviews and Reports Presents an Update on Acute Myeloid Leukemia Stem Cells: Origin, Characteristics, and Clinical Implications by Dr. David F. Claxton et al.
  2. The Historical Relationship Between Meis1 and Leukemia.
  3. All-Trans-Retinoic Acid Combined With Valproic Acid Can Promote Differentiation in Myeloid Leukemia Cells by an Autophagy Dependent Mechanism.
  4. Emerging Roles of Aldehyde Dehydrogenase Isoforms in Anti-cancer Therapy Resistance.
  5. A Novel Risk Defining System for Pediatric T-Cell Acute Lymphoblastic Leukemia From CCCG-ALL-2015 Group.
  6. A case of therapy-related acute lymphoblastic leukemia following the treatment of acute myeloid leukemia.
  7. Versatile Functional Energy Metabolism Platform Working From Research to Patient: An Integrated View of Cell Bioenergetics.
  8. Delving the depths of MRD negativity in acute myeloid leukemia.
  1. Stem Cell Rev Rep. 2022 Mar 14.
    Paper of April Issue of Stem Cell Reviews and Reports Presents an Update on Acute Myeloid Leukemia Stem Cells: Origin, Characteristics, and Clinical Implications by Dr. David F. Claxton et al.
    Suming Huang.
      
    DOI:  https://doi.org/10.1007/s12015-022-10365-5
  2. Adv Exp Med Biol. 2022 Mar 19.
    The Historical Relationship Between Meis1 and Leukemia.
    Neslihan Meriç, Fatih Kocabaş.
      Acute leukemia (AL) is a poor progressive resistant hematological disease, which has different subtypes and immunophenotypic properties according to leukemic blasts. AL is caused by genetic changes and associated with leukemia stem cells (LSCs), which determine its prognosis and endurance. LSCs are thought to be hematopoietic progenitor and stem cell (HPSCs)-like cells that underwent a malignant transformation. In addition to their low number, LSCs have the characteristics of self-renewal, resistance to chemotherapy, and relapse of leukemia. The myeloid ecotropic integration site-1 (MEIS1) protein is a member of the three-amino acid loop extension (TALE) family of homeodomain (HD) proteins that can bind to DNA sequence-specific manner. Studies have shown that overexpression of MEIS1 and associated cofactors involves tumorigenesis of numerous cancers. Historically, increased expression of Meis1 transcript as well as protein has been determined in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients. Moreover, resistance to conventional chemotherapy was observed in leukemic blast samples with high Meis1 content. In this review article, the molecular mechanism of the oncological role of the MEIS1 protein in leukemia and LSC is discussed. In addition, it was suggested that MEIS1 protein could be utilized as a possible treatment target in leukemia with an emphasis on the inhibition of MEIS1, which is overexpressed in LSC.
    Keywords:  Leukemia; Leukemia stem cells; MEIS1
    DOI:  https://doi.org/10.1007/5584_2021_705
  3. Front Oncol. 2022 ;12 848517
    All-Trans-Retinoic Acid Combined With Valproic Acid Can Promote Differentiation in Myeloid Leukemia Cells by an Autophagy Dependent Mechanism.
    Dalyia N Benjamin, Tracey R O'Donovan, Kristian B Laursen, Nina Orfali, Mary R Cahill, Nigel P Mongan, Lorraine J Gudas, Sharon L McKenna.
      Acute myeloid leukemia (AML) is an aggressive blood cancer with an overall survival of 30%. One form of AML, acute promyelocytic leukemia (APL) has become more than 90% curable with differentiation therapy, consisting of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). Application of differentiation therapy to other AML subtypes would be a major treatment advance. Recent studies have indicated that autophagy plays a key role in the differentiation of ATRA-responsive APL cells. In this study, we have investigated whether differentiation could be enhanced in ATRA resistant cells by promoting autophagy induction with valproic acid (VPA). ATRA sensitive (NB4) and resistant leukemia cells (NB4R and THP-1) were co-treated with ATRA and valproic acid, followed by assessment of autophagy and differentiation. The combination of VPA and ATRA induced autophagic flux and promoted differentiation in ATRA-sensitive and -resistant cell lines. shRNA knockdown of ATG7 and TFEB autophagy regulators impaired both autophagy and differentiation, demonstrating the importance of autophagy in the combination treatment. These data suggest that ATRA combined with valproic acid can promote differentiation in myeloid leukemia cells by mechanism involving autophagy.
    Keywords:  AML; APL; ATG7; ATRA; TFEB; autophagy; differentiation; valproic acid
    DOI:  https://doi.org/10.3389/fonc.2022.848517
  4. Front Med (Lausanne). 2022 ;9 795762
    Emerging Roles of Aldehyde Dehydrogenase Isoforms in Anti-cancer Therapy Resistance.
    Michele Zanoni, Sara Bravaccini, Francesco Fabbri, Chiara Arienti.
      Aldehyde dehydrogenases (ALDHs) are a family of detoxifying enzymes often upregulated in cancer cells and associated with therapeutic resistance. In humans, the ALDH family comprises 19 isoenzymes active in the majority of mammalian tissues. Each ALDH isoform has a specific differential expression pattern and most of them have individual functional roles in cancer. ALDHs are overexpressed in subpopulations of cancer cells with stem-like features, where they are involved in several processes including cellular proliferation, differentiation, detoxification and survival, participating in lipids and amino acid metabolism and retinoic acid synthesis. In particular, ALDH enzymes protect cancer cells by metabolizing toxic aldehydes in less reactive and more soluble carboxylic acids. High metabolic activity as well as conventional anticancer therapies contribute to aldehyde accumulation, leading to DNA double strand breaks (DSB) through the generation of reactive oxygen species (ROS) and lipid peroxidation. ALDH overexpression is crucial not only for the survival of cancer stem cells but can also affect immune cells of the tumour microenvironment (TME). The reduction of ROS amount and the increase in retinoic acid signaling impairs immunogenic cell death (ICD) inducing the activation and stability of immunosuppressive regulatory T cells (Tregs). Dissecting the role of ALDH specific isoforms in the TME can open new scenarios in the cancer treatment. In this review, we summarize the current knowledge about the role of ALDH isoforms in solid tumors, in particular in association with therapy-resistance.
    Keywords:  aldehyde dehydrogenase; cancer stem cell; double strand brakes (DSB); immunosuppression; therapeutic resistance
    DOI:  https://doi.org/10.3389/fmed.2022.795762
  5. Front Oncol. 2022 ;12 841179
    A Novel Risk Defining System for Pediatric T-Cell Acute Lymphoblastic Leukemia From CCCG-ALL-2015 Group.
    Xiaoming Liu, Yao Zou, Li Zhang, Ye Guo, Yumei Chen, Wenyu Yang, Xiaojuan Chen, Shuchun Wang, Yingchi Zhang, Min Ruan, Lixian Chang, Xiaoyan Zhang, Beibei Zhao, Ranran Zhang, Aoli Zhang, Lipeng Liu, Luyang Zhang, Meihui Yi, Xiaofan Zhu.
      Objective: T-cell acute lymphoblastic leukemia (T-ALL) is a rare hematological malignancy with a poor prognosis. The present study aims to identify the precise risk grouping of children with T-ALL.Methods: We analyzed the outcomes for 105 consecutive patients treated using the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005706) between 2015 and 2020 in our center. Nine out of 21 clinical and biological indicators were selected for the new scoring system based on the analysis in this study.
    Results: The 5-year overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) rates for the 105 patients were 83.1 ± 4.8%, 72.4 ± 5.6%, and 78.4 ± 3.6%, respectively. Based on the new scoring system, 90 evaluable children were regrouped into low-risk (n=22), intermediate-risk (n=50), and high-risk (n=18) groups. The 5-year survival (OS, EFS, and RFS) rates for all patients in the low-risk group were 100%, significantly higher than the rates for those in the intermediate-risk group (91.2 ± 5.2%, 74.4 ± 8.6%, and 82.5 ± 6.2%, respectively) and high-risk group (59.0 ± 13.2%, 51.9 ± 12.4%, and 51.9 ± 12.4%, respectively) (all P values < 0.01).
    Conclusion: The CCCG-ALL-2015 program significantly improved the treatment outcomes for childhood T-ALL as compared with the CCCG-ALL-2008 protocol. Our new refined risk grouping system showed better stratification among pediatric T-ALL patients and better potential in evaluating therapeutic efficacy.
    Keywords:  CCCG-ALL-2015; T-cell acute lymphoblastic leukemia (T-ALL); children; efficacy; risk
    DOI:  https://doi.org/10.3389/fonc.2022.841179
  6. Leuk Res Rep. 2022 ;17 100297
    A case of therapy-related acute lymphoblastic leukemia following the treatment of acute myeloid leukemia.
    Sufana Shikdar, Yuan Ying, Mohamad Khawandanah.
      Therapy-related acute lymphoblastic leukemia represents a distinct entity associated with inferior survival compared with de novo acute lymphoblastic leukemia. It consists of a subset of patients who have had exposure to chemotherapy or radiation for a previous malignancy. Here, we describe a case of acute myeloid leukemia who later developed precursor B cell acute lymphoblastic leukemia and discuss the current relevant literature. Our case highlights the importance of classifying therapy-related acute lymphoblastic leukemia as a separate as entity based on its biologic and clinical features.
    Keywords:  Acute myeloid leukemia; Secondary leukemia; Therapy-related acute lymphoblastic leukemia
    DOI:  https://doi.org/10.1016/j.lrr.2022.100297
  7. Front Toxicol. 2021 ;3 750431
    Versatile Functional Energy Metabolism Platform Working From Research to Patient: An Integrated View of Cell Bioenergetics.
    Sylvain Loric, Marc Conti.
      Mitochondrial dysfunctions that were not discovered during preclinical and clinical testing have been responsible for at least restriction of use as far as withdrawal of many drugs. To solve mitochondrial machinery complexity, integrative methodologies combining different data, coupled or not to mathematic modelling into systems biology, could represent a strategic way but are still very hard to implement. These technologies should be accurate and precise to avoid accumulation of errors that can lead to misinterpretations, and then alter prediction efficiency. To address such issue, we have developed a versatile functional energy metabolism platform that can measure quantitatively, in parallel, with a very high precision and accuracy, a high number of biological parameters like substrates or enzyme cascade activities in essential metabolism units (glycolysis, respiratory chain ATP production, oxidative stress...) Its versatility (our platform works on either cell lines or small animals and human samples) allows cell metabolism pathways fine tuning comparison from preclinical to clinical studies. Applied here to OXPHOS and/or oxidative stress as an example, it allows discriminating compounds with acute toxic effects but, most importantly, those inducing low noise chronic ones.
    Keywords:  automatisation; cell energetics; functional metabolism; oxidative stress; oxphos
    DOI:  https://doi.org/10.3389/ftox.2021.750431
  8. Haematologica. 2022 Mar 17.
    Delving the depths of MRD negativity in acute myeloid leukemia.
    Sylvie D Freeman.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2022.280747
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