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Best Practice & Research. Clinical... Sep 2020Artificial intelligence, and more narrowly machine-learning, is beginning to expand humanity's capacity to analyze increasingly large and complex datasets. Advances in... (Review)
Review
Artificial intelligence, and more narrowly machine-learning, is beginning to expand humanity's capacity to analyze increasingly large and complex datasets. Advances in computer hardware and software have led to breakthroughs in multiple sectors of our society, including a burgeoning role in medical research and clinical practice. As the volume of medical data grows at an apparently exponential rate, particularly since the human genome project laid the foundation for modern genetic inquiry, informatics tools like machine learning are becoming crucial in analyzing these data to provide meaningful tools for diagnostic, prognostic, and therapeutic purposes. Within medicine, hematologic diseases can be particularly challenging to understand and treat given the increasingly complex and intercalated genetic, epigenetic, immunologic, and regulatory pathways that must be understood to optimize patient outcomes. In acute myeloid leukemia (AML), new developments in machine learning algorithms have enabled a deeper understanding of disease biology and the development of better prognostic and predictive tools. Ongoing work in the field brings these developments incrementally closer to clinical implementation.
Topics: Genome, Human; Human Genome Project; Humans; Leukemia, Myeloid, Acute; Machine Learning
PubMed: 33038981
DOI: 10.1016/j.beha.2020.101192 -
Haematologica May 2021
Topics: Animals; Leukemia, Myeloid, Acute; Mice; T-Lymphocytes; Vaccines
PubMed: 33538155
DOI: 10.3324/haematol.2020.277103 -
Journal of Experimental & Clinical... Oct 2023Acute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible... (Review)
Review
Acute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible causes of which are transcriptional or epigenetic alterations, impaired apoptosis, and excessive cell proliferation. This neoplasm has a high rate of resistance to anticancer therapies and thus a high risk of relapse and mortality because of both the biological diversity of the patient and intratumoral heterogeneity due to the acquisition of new somatic changes. For more than 40 years, the old gold standard "one size fits all" treatment approach included intensive chemotherapy treatment with anthracyclines and cytarabine.The manuscript first traces the evolution of the understanding of the pathology from the 1970s to the present. The enormous strides made in its categorization prove to be crucial for risk stratification, enabling an increasingly personalized diagnosis and treatment approach.Subsequently, we highlight how, over the past 15 years, technological advances enabling single cell RNA sequencing and T-cell modification based on the genomic tools are affecting the classification and treatment of AML. At the dawn of the new millennium, the advent of high-throughput next-generation sequencing technologies has enabled the profiling of patients evidencing different facets of the same disease, stratifying risk, and identifying new possible therapeutic targets that have subsequently been validated. Currently, the possibility of investigating tumor heterogeneity at the single cell level, profiling the tumor at the time of diagnosis or after treatments exist. This would allow the identification of underrepresented cellular subclones or clones resistant to therapeutic approaches and thus responsible for post-treatment relapse that would otherwise be difficult to detect with bulk investigations on the tumor biopsy. Single-cell investigation will then allow even greater personalization of therapy to the genetic and transcriptional profile of the tumor, saving valuable time and dangerous side effects. The era of personalized medicine will take a huge step forward through the disclosure of each individual piece of the complex puzzle that is cancer pathology, to implement a "tailored" therapeutic approach based also on engineered CAR-T cells.
Topics: Humans; Receptors, Chimeric Antigen; Single-Cell Gene Expression Analysis; Leukemia, Myeloid, Acute; Cytarabine; Recurrence
PubMed: 37803464
DOI: 10.1186/s13046-023-02841-8 -
Blood Jan 2023
Topics: Humans; Aged; Aminopyridines; Triazines; Leukemia, Myeloid, Acute
PubMed: 36633887
DOI: 10.1182/blood.2022016946 -
Cell Communication and Signaling : CCS Mar 2023Heme oxygenase-1 (HO-1), a heme-degrading enzyme, is proven to have anti-apoptotic effects in several malignancies. In addition, HO-1 is reported to cause... (Review)
Review
BACKGROUND
Heme oxygenase-1 (HO-1), a heme-degrading enzyme, is proven to have anti-apoptotic effects in several malignancies. In addition, HO-1 is reported to cause chemoresistance and increase cell survival. Growing evidence indicates that HO-1 contributes to the course of hematological malignancies as well. Here, the expression pattern, prognostic value, and the effect of HO-1 targeting in HMs are discussed.
MAIN BODY
According to the recent literature, it was discovered that HO-1 is overexpressed in myelodysplastic syndromes (MDS), chronic myeloid leukemia (CML), acute myeloblastic leukemia (AML), and acute lymphoblastic leukemia (ALL) cells and is associated with high-risk disease. Furthermore, in addition to HO-1 expression by leukemic and MDS cells, CML, AML, and ALL leukemic stem cells express this protein as well, making it a potential target for eliminating minimal residual disease (MRD). Moreover, it was concluded that HO-1 induces tumor progression and prevents apoptosis through various pathways.
CONCLUSION
HO-1 has great potential in determining the prognosis of leukemia and MDS patients. HO-1 induces resistance to several chemotherapeutic agents as well as tyrosine kinase inhibitors and following its inhibition, chemo-sensitivity increases. Moreover, the exact role of HO-1 in Chronic Lymphocytic Leukemia (CLL) is yet unknown. While findings illustrate that MDS and other leukemic patients could benefit from HO-1 targeting. Future studies can help broaden our knowledge regarding the role of HO-1 in MDS and leukemia. Video abstract.
Topics: Humans; Heme Oxygenase-1; Prognosis; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
PubMed: 36915102
DOI: 10.1186/s12964-023-01074-8 -
British Journal of Haematology Jan 2020Comprehensive cataloguing of the acute myeloid leukaemia (AML) genome has revealed a high frequency of mutations and deletions in epigenetic factors that are frequently... (Review)
Review
Comprehensive cataloguing of the acute myeloid leukaemia (AML) genome has revealed a high frequency of mutations and deletions in epigenetic factors that are frequently linked to treatment resistance and poor patient outcome. In this review, we discuss how the epigenetic mechanisms that underpin normal haematopoiesis are subverted in AML, and in particular how these processes are altered in childhood and adolescent leukaemias. We also provide a brief summary of the burgeoning field of epigenetic-based therapies, and how AML treatment might be improved through provision of better conceptual frameworks for understanding the pleiotropic molecular effects of epigenetic disruption.
Topics: Adolescent; Child; Drug Resistance, Neoplasm; Epigenesis, Genetic; Hematopoiesis; Humans; Leukemia, Myeloid, Acute; Mutation
PubMed: 31804725
DOI: 10.1111/bjh.16361 -
Bone Marrow Transplantation Jan 2022Imagine you and your colleagues have done 1000 transplants in persons with acute myeloid leukaemia (AML) in 1st remission. 5 percent of the 20 percent of recipients...
Imagine you and your colleagues have done 1000 transplants in persons with acute myeloid leukaemia (AML) in 1st remission. 5 percent of the 20 percent of recipients relapsing posttransplant have an isolated central nervous system relapse. You are curious and want to know whether there is anything special about this 5 percent, specifically whether this risk corelates with any pretransplant clinical and laboratory co-variates. You have extensive clinical data and some typical laboratory data on all 1000 but you suspect the culprit is mutation topography. What to do? Fortunately you have bio-banked DNA from the 1000. If resources and monies are not limiting you can do targeted or next generation sequencing on all 1000 DNA samples and off you go. However, most of us lack unlimited resources and monies. How can you sensibly and efficiently tackle this research problem? The answer is a case-cohort design study. In the typescript which follows Profs. Cai and Kim explain how to accomplish this. If you follow their advice you may need only to analyze samples from < 300 recipients rather than 1000 to test your hypothesis. They explain how to design such a study and provide references to estimate sample size.Sadly, their typescript will not tell you how to get funding for the study, whish poor devil who will have to write the protocol, worse, who will shepherd it though endless committees for approval and the like. Help on these issues is outside the scope of our statistics series. In this context we suggest advice from Woody Allen's article in the New Yorker: The Kugelmass Episode (April 24, 1977). When Prof. Kugelmass (English, City College) tells his analyst Dr. Mandel he has fallen in love with Emma Bovary who died of arsenic poisoning near Rouen, France 120 years earlier the analyst says: After all, I'm an analyst, not a magician. Kugelmass' reply: Then perhaps what I need is a magician and is off to Coney Island to find one. Good luck, the magician may still be there! (Note: This typescript is R-rated. It contains an equation.)Robert Peter Gale, Imperial College London, and Mei-Jie Zhang, Medical College of Wisconsin and CIBMTR.
Topics: Cohort Studies; France; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Neoplasm Recurrence, Local
PubMed: 34400795
DOI: 10.1038/s41409-021-01433-4 -
British Journal of Haematology Jan 2020Acute myeloid leukaemia (AML) is a heterogeneous disease in which prognosis is determined by cytogenetic and molecular aberrations as well as patient-related factors,... (Review)
Review
Acute myeloid leukaemia (AML) is a heterogeneous disease in which prognosis is determined by cytogenetic and molecular aberrations as well as patient-related factors, including age, prior haematologic disorders, and comorbidities. Despite the diverse disease biology, the standard of care for remission induction therapy has changed very little since its inception in 1973. Next generation sequencing has helped to increase our knowledge of the disease pathogenesis, allowing us to develop targeted and possibly more effective treatment options. Seven new agents have been approved for the treatment of AML since 2017, all of which are directed toward a specific molecular subtype or patient population. With the advent of these therapies, a more optimal, patient-specific approach rather than the historical 'one-size fits all' model can be utilised. This review will discuss the role of these novel therapies in the remission induction setting.
Topics: Disease-Free Survival; High-Throughput Nucleotide Sequencing; Humans; Leukemia, Myeloid, Acute; Precision Medicine; Remission Induction
PubMed: 31828798
DOI: 10.1111/bjh.16353 -
Blood Aug 2022
Topics: Humans; Leukemia, Myeloid, Acute; Neoplasm Recurrence, Local; Neoplasm, Residual; Prospective Studies
PubMed: 35925646
DOI: 10.1182/blood.2022017138 -
Blood Jan 2022
Topics: Cell Differentiation; Humans; Leukemia, Myeloid, Acute
PubMed: 35050335
DOI: 10.1182/blood.2021013814