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Rhode Island Medical Journal (2013) Apr 2020Acute myeloid leukemia (AML) is a malignancy of the stem cell precursors of the myeloid lineage (red blood cells, platelets, and white blood cells other than B and T... (Review)
Review
Acute myeloid leukemia (AML) is a malignancy of the stem cell precursors of the myeloid lineage (red blood cells, platelets, and white blood cells other than B and T cells). Like other malignancies, it is due to genetic variations that lead to neoplastic changes and clonal proliferation. AML remains a rare malignancy, accounting for only 1.2% of all new cancer diagnoses in the United States per year, but it accounts for close to one third of all leukemias diagnosed.* For much of the 20th and early 21st century treatment paradigms were unchanged with survival curves remaining stagnant for many decades. Recent changes in our understanding of the genetic variations in the disease have led to some promising new therapies with hopes for improved outcomes in the future. Below we review the definitions, diagnosis and classification of AML and how this affects the evolving treatment paradigm of AML.
Topics: Antineoplastic Agents; Forecasting; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Recurrence; Treatment Outcome
PubMed: 32236160
DOI: No ID Found -
Annals of Hematology Aug 2023Myeloid sarcoma (MS) is a distinct entity among myeloid neoplasms defined as a tumour mass of myeloid blasts occurring at an anatomical site other than the bone marrow,... (Review)
Review
Myeloid sarcoma (MS) is a distinct entity among myeloid neoplasms defined as a tumour mass of myeloid blasts occurring at an anatomical site other than the bone marrow, in most cases concomitant with acute myeloid leukaemia (AML), rarely without bone marrow involvement. MS may also represent the blast phase of chronic myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS). However, the clinical and molecular heterogeneity of AML, as highlighted by the 2022 World Health Organization (WHO) and International Consensus (ICC) classifications, indirectly define MS more as a set of heterogeneous and proteiform diseases, rather than a homogeneous single entity. Diagnosis is challenging and relies mainly on histopathology, immunohistochemistry, and imaging. Molecular and cytogenetic analysis of MS tissue, particularly in isolated cases, should be performed to refine the diagnosis, and thus assign prognosis guiding treatment decisions. If feasible, systemic therapies used in AML remission induction should be employed, even in isolated MS. Role and type of consolidation therapy are not univocally acknowledged, and systemic therapies, radiotherapy, or allogeneic hematopoietic stem cell transplantation (allo-HSCT) should be considered. In the present review, we discuss recent information on MS, focusing on diagnosis, molecular findings, and treatments also considering targetable mutations by recently approved AML drugs.
Topics: Humans; Sarcoma, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Myeloproliferative Disorders; Hematopoietic Stem Cell Transplantation
PubMed: 37286874
DOI: 10.1007/s00277-023-05288-1 -
American Journal of Hematology Oct 2018Outcome in patients with acute myeloid leukemia (AML) ranges from death within a few days of beginning treatment (treatment related mortality, TRM) to likely cure. The... (Review)
Review
Outcome in patients with acute myeloid leukemia (AML) ranges from death within a few days of beginning treatment (treatment related mortality, TRM) to likely cure. The major reason patients are not cured is resistance to treatment, often manifested as relapse from remission, rather than, even in older patients, TRM, whose incidence is decreasing. Knowledge of the pre-treatment mutation status of various genes has improved our ability to assign initial treatment and, of particular importance, knowledge of whether patients ostensibly in remission have measurable residual disease should influence subsequent management. Several new drugs have been approved by the FDA and we discuss their role in treatment.
Topics: Abnormal Karyotype; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Disease-Free Survival; Drug Resistance, Neoplasm; Drugs, Investigational; Female; Genes, Neoplasm; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Molecular Targeted Therapy; Mutation; Patient Selection; Prognosis; Remission Induction; Risk Assessment
PubMed: 30328165
DOI: 10.1002/ajh.25214 -
Cell Nov 2020Brain metastasis (br-met) develops in an immunologically unique br-met niche. Central nervous system-native myeloid cells (CNS-myeloids) and bone-marrow-derived myeloid...
Brain metastasis (br-met) develops in an immunologically unique br-met niche. Central nervous system-native myeloid cells (CNS-myeloids) and bone-marrow-derived myeloid cells (BMDMs) cooperatively regulate brain immunity. The phenotypic heterogeneity and specific roles of these myeloid subsets in shaping the br-met niche to regulate br-met outgrowth have not been fully revealed. Applying multimodal single-cell analyses, we elucidated a heterogeneous but spatially defined CNS-myeloid response during br-met outgrowth. We found Ccr2 BMDMs minimally influenced br-met while CNS-myeloid promoted br-met outgrowth. Additionally, br-met-associated CNS-myeloid exhibited downregulation of Cx3cr1. Cx3cr1 knockout in CNS-myeloid increased br-met incidence, leading to an enriched interferon response signature and Cxcl10 upregulation. Significantly, neutralization of Cxcl10 reduced br-met, while rCxcl10 increased br-met and recruited VISTA PD-L1 CNS-myeloid to br-met lesions. Inhibiting VISTA- and PD-L1-signaling relieved immune suppression and reduced br-met burden. Our results demonstrate that loss of Cx3cr1 in CNS-myeloid triggers a Cxcl10-mediated vicious cycle, cultivating a br-met-promoting, immune-suppressive niche.
Topics: Animals; Bone Marrow Cells; Brain Neoplasms; CX3C Chemokine Receptor 1; Central Nervous System; Chemokine CXCL10; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunosuppression Therapy; Interferons; Macrophages; Membrane Proteins; Mice, Inbred C57BL; Mice, Knockout; Myeloid Cells; Neutralization Tests; Phenotype; T-Lymphocytes; Transcriptome
PubMed: 33113353
DOI: 10.1016/j.cell.2020.09.064 -
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 -
Journal of Experimental & Clinical... Dec 2023Myeloid cells (granulocytes and monocytes/macrophages) play an important role in neuroblastoma. By inducing a complex immunosuppressive network, myeloid cells pose a... (Review)
Review
Myeloid cells (granulocytes and monocytes/macrophages) play an important role in neuroblastoma. By inducing a complex immunosuppressive network, myeloid cells pose a challenge for the adaptive immune system to eliminate tumor cells, especially in high-risk neuroblastoma. This review first summarizes the pro- and anti-tumorigenic functions of myeloid cells, including granulocytes, monocytes, macrophages, and myeloid-derived suppressor cells (MDSC) during the development and progression of neuroblastoma. Secondly, we discuss how myeloid cells are engaged in the current treatment regimen and explore novel strategies to target these cells in neuroblastoma. These strategies include: (1) engaging myeloid cells as effector cells, (2) ablating myeloid cells or blocking the recruitment of myeloid cells to the tumor microenvironment and (3) reprogramming myeloid cells. Here we describe that despite their immunosuppressive traits, tumor-associated myeloid cells can still be engaged as effector cells, which is clear in anti-GD2 immunotherapy. However, their full potential is not yet reached, and myeloid cell engagement can be enhanced, for example by targeting the CD47/SIRPα axis. Though depletion of myeloid cells or blocking myeloid cell infiltration has been proven effective, this strategy also depletes possible effector cells for immunotherapy from the tumor microenvironment. Therefore, reprogramming of suppressive myeloid cells might be the optimal strategy, which reverses immunosuppressive traits, preserves myeloid cells as effectors of immunotherapy, and subsequently reactivates tumor-infiltrating T cells.
Topics: Humans; Neuroblastoma; Neoplasms; Myeloid Cells; Immunotherapy; Myeloid-Derived Suppressor Cells; Macrophages; Tumor Microenvironment
PubMed: 38087370
DOI: 10.1186/s13046-023-02913-9 -
Cancer Cell Feb 2023Cancer immunotherapy critically depends on fitness of cytotoxic and helper T cell responses. Dysfunctional cytotoxic T cell states in the tumor microenvironment (TME)...
Cancer immunotherapy critically depends on fitness of cytotoxic and helper T cell responses. Dysfunctional cytotoxic T cell states in the tumor microenvironment (TME) are a major cause of resistance to immunotherapy. Intratumoral myeloid cells, particularly blood-borne myeloids (bbm), are key drivers of T cell dysfunction in the TME. We show here that major histocompatibility complex class II (MHCII)-restricted antigen presentation on bbm is essential to control the growth of brain tumors. Loss of MHCII on bbm drives dysfunctional intratumoral tumor-reactive CD8 T cell states through increased chromatin accessibility and expression of Tox, a critical regulator of T cell exhaustion. Mechanistically, MHCII-dependent activation of CD4 T cells restricts myeloid-derived osteopontin that triggers a chronic activation of NFAT2 in tumor-reactive CD8 T cells. In summary, we provide evidence that MHCII-restricted antigen presentation on bbm is a key mechanism to directly maintain functional cytotoxic T cell states in brain tumors.
Topics: Humans; T-Lymphocytes, Cytotoxic; Antigen Presentation; CD8-Positive T-Lymphocytes; Histocompatibility Antigens Class II; Brain Neoplasms; Tumor Microenvironment
PubMed: 36638785
DOI: 10.1016/j.ccell.2022.12.007 -
Blood Jan 2023
Topics: Humans; Aged; Aminopyridines; Triazines; Leukemia, Myeloid, Acute
PubMed: 36633887
DOI: 10.1182/blood.2022016946 -
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