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Pathobiology : Journal of... 2024Disease progression in myelodysplastic syndromes (MDS), myelodysplastic-myeloproliferative neoplasms (MDS/MPN), and myeloproliferative neoplasms (MPN), altogether... (Review)
Review
Disease progression in myelodysplastic syndromes (MDS), myelodysplastic-myeloproliferative neoplasms (MDS/MPN), and myeloproliferative neoplasms (MPN), altogether referred to as myeloid neoplasms (MN), is a major source of mortality. Apart from transformation to acute myeloid leukemia, the clinical progression of MN is mostly due to the overgrowth of pre-existing hematopoiesis by the MN without an additional transforming event. Still, MN may evolve along other recurrent yet less well-known scenarios: (1) acquisition of MPN features in MDS or (2) MDS features in MPN, (3) progressive myelofibrosis (MF), (4) acquisition of chronic myelomonocytic leukemia (CMML)-like characteristics in MPN or MDS, (5) development of myeloid sarcoma (MS), (6) lymphoblastic (LB) transformation, (7) histiocytic/dendritic outgrowths. These MN-transformation types exhibit a propensity for extramedullary sites (e.g., skin, lymph nodes, liver), highlighting the importance of lesional biopsies in diagnosis. Gain of distinct mutations/mutational patterns seems to be causative or at least accompanying several of the above-mentioned scenarios. MDS developing MPN features often acquire MPN driver mutations (usually JAK2), and MF. Conversely, MPN gaining MDS features develop, e.g., ASXL1, IDH1/2, SF3B1, and/or SRSF2 mutations. Mutations of RAS-genes are often detected in CMML-like MPN progression. MS ex MN is characterized by complex karyotypes, FLT3 and/or NPM1 mutations, and often monoblastic phenotype. MN with LB transformation is associated with secondary genetic events linked to lineage reprogramming leading to the deregulation of ETV6, IKZF1, PAX5, PU.1, and RUNX1. Finally, the acquisition of MAPK-pathway gene mutations may shape MN toward histiocytic differentiation. Awareness of all these less well-known MN-progression types is important to guide optimal individual patient management.
Topics: Humans; Granulocyte Precursor Cells; Myeloproliferative Disorders; Myelodysplastic Syndromes; Mutation; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid, Acute
PubMed: 37232015
DOI: 10.1159/000530940 -
Immunity Aug 2020Granulocyte-monocyte progenitors (GMPs) have been previously defined for their potential to generate various myeloid progenies such as neutrophils and monocytes....
Granulocyte-monocyte progenitors (GMPs) have been previously defined for their potential to generate various myeloid progenies such as neutrophils and monocytes. Although studies have proposed lineage heterogeneity within GMPs, it is unclear if committed progenitors already exist among these progenitors and how they may behave differently during inflammation. By combining single-cell transcriptomic and proteomic analyses, we identified the early committed progenitor within the GMPs responsible for the strict production of neutrophils, which we designate as proNeu1. Our dissection of the GMP hierarchy led us to further identify a previously unknown intermediate proNeu2 population. Similar populations could be detected in human samples. proNeu1s, but not proNeu2s, selectively expanded during the early phase of sepsis at the expense of monocytes. Collectively, our findings help shape the neutrophil maturation trajectory roadmap and challenge the current definition of GMPs.
Topics: Animals; Granulocyte Precursor Cells; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes; Myelopoiesis; Neutrophils; Single-Cell Analysis
PubMed: 32579887
DOI: 10.1016/j.immuni.2020.06.005 -
Indian Journal of Pathology &... Apr 2024
Topics: Humans; Inclusion Bodies; Granulocyte Precursor Cells; Microscopy; Male; Bone Marrow; Histocytochemistry; Female
PubMed: 38391365
DOI: 10.4103/ijpm.ijpm_33_22 -
Immunity Nov 2017Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during...
Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar but distinct monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6C) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of "neutrophil-like" monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independently mobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection.
Topics: Animals; Antigens, Ly; Cell Differentiation; Dendritic Cells; Granulocyte Precursor Cells; Leukosialin; Mice; Monocytes; Myeloid Progenitor Cells; Sequence Analysis, RNA; Transcriptome
PubMed: 29166589
DOI: 10.1016/j.immuni.2017.10.021 -
Haematologica Dec 2019
Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Cells; Combined Modality Therapy; Erythroid Cells; Follow-Up Studies; Granulocyte Precursor Cells; Humans; Myelodysplastic Syndromes; Prognosis; Retrospective Studies; Stem Cell Transplantation; Survival Rate
PubMed: 31004031
DOI: 10.3324/haematol.2018.212563 -
Blood Advances Nov 2019
Topics: Aniline Compounds; Granulocyte Precursor Cells; Humans; Leukemia, Myeloid, Acute; Pyrazines
PubMed: 31765477
DOI: 10.1182/bloodadvances.2019000775 -
Computer Methods and Programs in... Jan 2024
Topics: Humans; Leukemia, Myeloid, Acute; Image Processing, Computer-Assisted; Machine Learning; Algorithms; Granulocyte Precursor Cells
PubMed: 38708372
DOI: 10.1016/j.cmpb.2023.107852 -
Frontiers of Medicine Aug 2021t(8;21)(q22;q22) acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a high relapse rate in China. Two leukemic myeloblast populations...
t(8;21)(q22;q22) acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a high relapse rate in China. Two leukemic myeloblast populations (CD34CD117 and CD34CD117) were previously identified in t(8;21) AML, and CD34CD117 cell proportion was determined as an independent factor for this disease outcome. Here, we examined the impact of CD34CD117/CD34CD117 myeloblast-associated gene expression on t(8;21) AML clinical prognosis. In this study, 85 patients with t(8;21) AML were enrolled. The mRNA expression levels of CD34CD117-associated genes (LGALS1, EMP3, and CRIP1) and CD34CD117-associated genes (TRH, PLAC8, and IGLL1) were measured using quantitative reverse transcription PCR. Associations between gene expression and clinical outcomes were determined using Cox regression models. Results showed that patients with high LGALS1, EMP3, or CRIP1 expression had significantly inferior overall survival (OS), whereas those with high TRH or PLAC8 expression showed relatively favorable prognosis. Univariate analysis revealed that CD19, CD34CD117 proportion, KIT mutation, minimal residual disease (MRD), and expression levels of LGALS1, EMP3, CRIP1, TRH and PLAC8 were associated with OS. Multivariate analysis indicated that KIT mutation, MRD and CRIP1 and TRH expression levels were independent prognostic variables for OS. Identifying the clinical relevance of CD34CD117/CD34CD117 myeloblast-associated gene expression may provide new clinically prognostic markers for t(8;21) AML.
Topics: Gene Expression; Granulocyte Precursor Cells; Humans; Immunophenotyping; Leukemia, Myeloid, Acute; Membrane Glycoproteins; Prognosis; Proteins; Proto-Oncogene Proteins c-kit
PubMed: 33754282
DOI: 10.1007/s11684-021-0836-7 -
Myeloblast phenotypic changes in myelodysplasia. CD34 and CD117 expression abnormalities are common.American Journal of Clinical Pathology Jun 2006We used a new method of data presentation and analysis, termed antigen mapping, to characterize recurring myeloblast phenotypic abnormalities in a series of 28 cases of...
We used a new method of data presentation and analysis, termed antigen mapping, to characterize recurring myeloblast phenotypic abnormalities in a series of 28 cases of myelodysplastic syndrome (MDS), including refractory anemia with ringed sideroblasts (RARS), refractory anemia with multilineage dysplasia (RCMLD), and refractory anemia with excess blasts (RAEB). Abnormal patterns of CD34 and CD117 expression were present in 50% of RARS, 68% of RCMLD, and 100% of RAEB cases. The presence of decreased myeloblast CD45 density, increased CD13 and CD34 density, and increased expression of CD11c and CD4(dim) were MDS grade-related. There was a direct relationship between the number of myeloblast phenotypic abnormalities (phenotypic score) and MDS grade. The myeloblast phenotypic scores also were correlated highly with International Prognostic Scoring System scores and risk categories. We found the antigen mapping technique to be an efficient data presentation and analysis method for the detection of MDS-associated abnormalities of antigen distribution and density.
Topics: Aged; Aged, 80 and over; Anemia, Refractory, with Excess of Blasts; Antigens, CD34; Biomarkers; Bone Marrow; Epitope Mapping; Female; Granulocyte Precursor Cells; Humans; Immunophenotyping; Male; Middle Aged; Phenotype; Proto-Oncogene Proteins c-kit
PubMed: 16690488
DOI: 10.1309/j3et7rxd1x4bkdlf -
Current Opinion in Hematology Jan 2017Eosinophils are a subset of granulocytes generally associated with type 2 immune responses. They can contribute to protection against helminths but also mediate... (Review)
Review
PURPOSE OF REVIEW
Eosinophils are a subset of granulocytes generally associated with type 2 immune responses. They can contribute to protection against helminths but also mediate pro-inflammatory functions during allergic immune responses. Only recently, eosinophils were also found to exert many other functions such as regulation of glucose and fat metabolism, thermogenesis, survival of plasma cells, and antitumor activity. The mechanisms that control eosinophil development and survival are only partially understood.
RECENT FINDINGS
Here we review new findings regarding the role of cell-extrinsic and cell-intrinsic factors for eosinophilopoiesis and eosinophil homeostasis. Several reports provide new insights in the regulation of eosinophil development by transcription factors, miRNAs and epigenetic modifications. Danger signals like lipopolysaccharide or alarmins can activate eosinophils but also prolong their lifespan. We further reflect on the observations that eosinophil development is tightly controlled by the unfolded protein stress response and formation of cytoplasmic granules.
SUMMARY
Eosinophils emerge as important regulators of diverse biological processes. Their differentiation and survival is tightly regulated by factors that are still poorly understood. Newly identified pathways involved in eosinophilopoiesis and eosinophil homeostasis may lead to development of new therapeutic options for treatment of eosinophil-associated diseases.
Topics: Alarmins; Animals; Antigens, Differentiation, Myelomonocytic; Bone Marrow; Cell Differentiation; Cell Survival; Eosinophils; Gene Expression Regulation; Granulocyte Precursor Cells; Homeostasis; Humans; Interleukin-5; Leukopoiesis; MicroRNAs; Protein Binding; Signal Transduction; Transcription Factors
PubMed: 27673511
DOI: 10.1097/MOH.0000000000000293