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Acta Biochimica Et Biophysica Sinica Jun 2023Leukaemia is the common name for a group of malignant diseases of the haematopoietic system with complex classifications and characteristics. Remarkable progress has... (Review)
Review
Leukaemia is the common name for a group of malignant diseases of the haematopoietic system with complex classifications and characteristics. Remarkable progress has been made in basic research and preclinical studies for acute leukaemia compared to that of the many other types/subtypes of leukaemia, especially the exploration of the biological basis and application of immunotherapy in acute myeloid leukaemia (AML) and B-cell acute lymphoblastic leukaemia (B-ALL). In this review, we summarize the basic approaches to immunotherapy for leukaemia and focus on the research progress made in immunotherapy development for AML and ALL. Importantly, despite the advances made to date, big challenges still exist in the effectiveness of leukaemia immunotherapy, especially in AML. Therefore, we use AML as an example and summarize the mechanisms of tumour cell immune evasion, describe recently reported data and known therapeutic targets, and discuss the obstacles in finding suitable treatment targets and the results obtained in recent clinical trials for several types of single and combination immunotherapies, such as bispecific antibodies, cell therapies (CAR-T-cell treatment), and checkpoint blockade. Finally, we summarize novel immunotherapy strategies for treating lymphocytic leukaemia and clinical trial results.
Topics: Immunotherapy; Humans; Bone Marrow Transplantation; Cancer Vaccines; Tumor Escape; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 37272727
DOI: 10.3724/abbs.2023101 -
Nature Reviews. Cancer Mar 2020For two decades, leukaemia stem cells (LSCs) in chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) have been advanced paradigms for the cancer stem cell... (Review)
Review
For two decades, leukaemia stem cells (LSCs) in chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) have been advanced paradigms for the cancer stem cell field. In CML, the acquisition of the fusion tyrosine kinase BCR-ABL1 in a haematopoietic stem cell drives its transformation to become a LSC. In AML, LSCs can arise from multiple cell types through the activity of a number of oncogenic drivers and pre-leukaemic events, adding further layers of context and genetic and cellular heterogeneity to AML LSCs not observed in most cases of CML. Furthermore, LSCs from both AML and CML can be refractory to standard-of-care therapies and persist in patients, diversify clonally and serve as reservoirs to drive relapse, recurrence or progression to more aggressive forms. Despite these complexities, LSCs in both diseases share biological features, making them distinct from other CML or AML progenitor cells and from normal haematopoietic stem cells. These features may represent Achilles' heels against which novel therapies can be developed. Here, we review many of the similarities and differences that exist between LSCs in CML and AML and examine the therapeutic strategies that could be used to eradicate them.
Topics: Animals; Biomarkers, Tumor; Cell Transformation, Neoplastic; Disease Management; Disease Susceptibility; Drug Development; History, 20th Century; History, 21st Century; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Neoplastic Stem Cells; Research
PubMed: 31907378
DOI: 10.1038/s41568-019-0230-9 -
Annals of Oncology : Official Journal... Jun 2020
Topics: Adult; Follow-Up Studies; Humans; Leukemia, Myeloid, Acute
PubMed: 32171751
DOI: 10.1016/j.annonc.2020.02.018 -
Molecular Genetics and Metabolism Aug 2020Acute myeloid leukemia (AML) is a complex, heterogenous hematological malignancy caused by mutations in myeloid differentiation and proliferation. Response to therapy... (Review)
Review
Acute myeloid leukemia (AML) is a complex, heterogenous hematological malignancy caused by mutations in myeloid differentiation and proliferation. Response to therapy and long-term outcomes vary widely based on chromosomal and molecular aberrations. Many platforms have been used to characterize and stratify AML. Metabolomics, the global profiling of small molecules in a biological sample, has emerged in the last decade as an important tool for studying the metabolic dependency of cancer cells. Metabolic reprogramming is not only an important manifestation of AML but clinically relevant for diagnosis, risk stratification and targeted drug development. In this review, we discuss notable metabolic studies of the last decade and their application to novel therapies.
Topics: Animals; Biomarkers, Tumor; Humans; Leukemia, Myeloid, Acute; Metabolome
PubMed: 32457018
DOI: 10.1016/j.ymgme.2020.05.005 -
International Journal of Molecular... Jun 2022Acute myeloid leukaemia (AML) is defined as a malignant disorder of the bone marrow (BM) that is characterised by the clonal expansion and differentiation arrest of...
Acute myeloid leukaemia (AML) is defined as a malignant disorder of the bone marrow (BM) that is characterised by the clonal expansion and differentiation arrest of myeloid progenitor cells [...].
Topics: Bone Marrow; Bone Marrow Cells; Humans; Leukemia, Myeloid, Acute
PubMed: 35682932
DOI: 10.3390/ijms23116251 -
Annals of Hematology Aug 2022In recent years, an explosion of novel agents has shifted the treatment paradigm for patients with acute myeloid leukemia. The optimal place in therapy for many of these... (Review)
Review
In recent years, an explosion of novel agents has shifted the treatment paradigm for patients with acute myeloid leukemia. The optimal place in therapy for many of these novel agents remains unknown due to limited guidance from national guidelines and the way these agents were studied prior to entering the market. A critical evaluation of the literature and incorporation of oncology stewardship principles can be helpful in determining an optimal place for these agents while being mindful of the overall cost that is associated with therapies. The purpose of this review is to critically evaluate the efficacy and safety data for five controversial agents and provide examples of the use of stewardship practices in determining their place in the treatment of acute myeloid leukemia.
Topics: Humans; Leukemia, Myeloid, Acute; Medical Oncology
PubMed: 35618780
DOI: 10.1007/s00277-022-04872-1 -
Hematology (Amsterdam, Netherlands) Dec 2023to review the current diagnostic and therapeutic landscape of AML in Latin America as a reflection of other low- and middle-income countries and regions of the world.... (Review)
Review
OBJECTIVE
to review the current diagnostic and therapeutic landscape of AML in Latin America as a reflection of other low- and middle-income countries and regions of the world. Encompassing both acute promyelocytic and non-promyelocytic disease types.
METHODS
We reviewed the literature and study registries concerning epidemiological features of patients with AML/APL treated in Latin America, as well as evaluated diagnostic and genetic stratification and patient fitness assessment challenges, the importance of early mortality and supportive care capacity, intensive and non-intensive chemotherapy alternatives, consolidation, and maintenance strategies including novel agents and hematopoietic stem cell transplantation.
RESULTS
Although most of the current technologies and treatment options are available in the region, a significant fraction of patients have only limited access to them. In addition, mortality in the first weeks from diagnosis is higher in the region compared to developed countries.
CONCLUSIONS
Disparities in access to technologies, supportive care capacity, and availability of novel agents and HSCT hinder results in our region, reflecting barriers common to other LMICs. Recent developments in the diagnosis and treatment of this disease must be implemented through education, collaborative clinical research, and advocacy to improve outcomes.
Topics: Humans; Leukemia, Promyelocytic, Acute; Tretinoin; Latin America; Leukemia, Myeloid, Acute; Hematopoietic Stem Cell Transplantation; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36607152
DOI: 10.1080/16078454.2022.2158015 -
Leukemia Dec 2022We used data from 852 consecutive subjects with myelodysplastic neoplasms (MDS) diagnosed according to the 2016 (revised 4th) World Health Organization (WHO) criteria to...
We used data from 852 consecutive subjects with myelodysplastic neoplasms (MDS) diagnosed according to the 2016 (revised 4th) World Health Organization (WHO) criteria to evaluate the 2022 (5th) edition WHO classification of MDS. 30 subjects previously classified as MDS with an NPM1 mutation were re-classified as acute myeloid leukaemia (AML). 9 subjects previously classified as MDS-U were re-classified to clonal cytopenia of undetermined significance (CCUS). The remaining 813 subjects were diagnosed as: MDS-5q (N = 11 [1%]), MDS-SF3B1 (N = 70 [9%]), MDS-biTP53 (N = 53 [7%]), MDS-LB (N = 293 [36%]), MDS-h (N = 80 [10%]), MDS-IB1 (N = 161 [20%]), MDS-IB2 (N = 103 [13%]) and MDS-f (N = 42 [5%]) and MDS-biTP53 (N = 53 [7%]). 34 of these subjects came from the 53 (64%) MDS-biTP53 previously diagnosed as MDS-EB. Median survival of subjects classified as MDS using the WHO 2022 criteria was 45 months (95% Confidence Interval [CI], 34, 56 months). Subjects re-classified as MDS-biTP53 and MDS-f had significantly briefer median survivals compared with other MDS sub-types (10 months, [8, 12 months] and 15 months [8, 23 months]). In conclusion, our analyses support the refinements made in the WHO 2022 proposal.
Topics: Humans; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; World Health Organization; Mutation
PubMed: 36224330
DOI: 10.1038/s41375-022-01718-7 -
Palliative & Supportive Care Feb 2021
Topics: Humans; Leukemia, Myeloid, Acute; Patient Acceptance of Health Care
PubMed: 32662378
DOI: 10.1017/S147895152000053X -
Blood May 2021The retinoic acid receptors (RARA, RARB, and RARG) are ligand-regulated nuclear receptors that act as transcriptional switches. These master genes drew significant... (Review)
Review
The retinoic acid receptors (RARA, RARB, and RARG) are ligand-regulated nuclear receptors that act as transcriptional switches. These master genes drew significant interest in the 1990s because of their key roles in embryogenesis and involvement in a rare malignancy, acute promyelocytic leukemia (APL), in which the RARA (and very rarely, RARG or RARB) genes are rearranged, underscoring the central role of deregulated retinoid signaling in leukemogenesis. Several recent provocative observations have revived interest in the roles of retinoids in non-APL acute myeloid leukemia (AML), as well as in normal hematopoietic differentiation. We review the role of retinoids in hematopoiesis, as well as in the treatment of non-APL AMLs. From this perspective, broader uses of retinoids in the management of hematopoietic tumors are discussed.
Topics: Animals; Hematopoiesis; Humans; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Receptors, Cytoplasmic and Nuclear; Retinoids
PubMed: 33651885
DOI: 10.1182/blood.2020010100