| Myeloblast | |
|---|---|
 Myeloblast | |
| Identifiers | |
| TH | H2.00.04.3.04002 |
| FMA | 83524 |
| Anatomical terms of microanatomy | |
The myeloblast is a unipotent stem cell which differentiates into the effectors of the granulocyte series. It is found in the bone marrow. Stimulation of myeloblasts by G-CSF and other cytokines triggers maturation, differentiation, proliferation and cell survival. [1]
Myeloblasts reside extravascularly in the bone marrow. Hematopoiesis takes place in the extravascular cavities between the sinuses of the marrow. The wall of the sinuses is composed of two different types of cells, endothelial cells and adventitial reticular cells. The hemopoietic cells are aligned in cords or wedges between these sinuses, with myeloblasts and other granular progenitors concentrated in the subcortical regions of these hemopoietic cords.
Myeloblasts are rather small cells with a diameter between 14 and 18μm. The major part is occupied by a large oval nucleus composed of very fine nonaggregated chromatin and possessing 3 or more nucleoli. The cytoplasm has a basophilic character and is devoid of granules, which is a major difference from the myeloblast's successor, the promyelocyte. The nucleolus is the site of assembly of ribosomal proteins, which are located in various particles dispersed over the cytoplasm. Mitochondria are present but have a rather small size.
The main features that distinguish a myeloblast from a lymphoblast upon microscopic examination are the presence of cytoplasmic granules, the lesser degree of condensation in the nuclear chromatin, and the increased prominence of the nucleoli. [2]
These cells descend from the primitive reticulum cells, which are found in the stroma of the marrow. There is also an intermediate phase between the myeloblast and these primitive reticulum cells, namely the hemocytoblast. At this time several developing blood cell lines are available, like erythropoiesis and thrombopoiesis. Granulopoiesis is regulated by humoral agents, like colony-stimulating factor (CSF) and interleukin 3.
Granulopoiesis consists of 5 stages, in which the myeloblast is the first recognizable cell. Next in the differentiation sequence is the monoblast and the promyelocyte, which can develop into one of three different precursor cells: the neutrophilic, basophilic or eosinophilic myelocyte. This proliferation takes five divisions before the final stage is obtained. These divisions all take place in the first three stages of granulopoiesis.
The most common problem with malfunctioning myeloblasts is acute myeloblastic leukemia. [3] [4] The main clinical features of acute myeloblastic leukemia are caused by failure of hemopoiesis with anemia, hemorrhage and infection as a result. There is a progressive accumulation of leukemic cells, because some blast progenitor cells renew themselves and have a limited differentiated division. Sometimes acute myeloblastic leukemia can be initiated by earlier hematologic disorders, like myelodysplastic syndrome, pancytopenia, or hypoplasia of the bone marrow.
Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten billion to a hundred billion new blood cells are produced per day, in order to maintain steady state levels in the peripheral circulation.
A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include fatigue, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia.
Erythropoiesis is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is activation and growth of mutated cells in the bone marrow. This is most often associated with a somatic mutation in the JAK2, CALR, or MPL genes. In PMF, the bony aspects of bone marrow are remodeled in a process called osteosclerosis; in addition, fibroblast secrete collagen and reticulin proteins that are collectively referred to as (fibrosis). These two pathological processes compromise the normal function of bone marrow resulting in decreased production of blood cells such as erythrocytes, granulocytes and megakaryocytes, the latter cells responsible for the production of platelets.
Cyclic neutropenia (CyN) is a rare hematologic disorder and form of congenital neutropenia that tends to occur approximately every three weeks and lasting for few days at a time due to changing rates of neutrophil production by the bone marrow. It causes a temporary condition with a low absolute neutrophil count and because the neutrophils make up the majority of circulating white blood cells it places the body at severe risk of inflammation and infection. In comparison to severe congenital neutropenia, it responds well to treatment with granulocyte colony-stimulating factor (filgrastim), which increases the neutrophil count, shortens the cycle length, as well decreases the severity and frequency of infections.
A myelocyte is a young cell of the granulocytic series, occurring normally in bone marrow.
Myeloid tissue, in the bone marrow sense of the word myeloid, is tissue of bone marrow, of bone marrow cell lineage, or resembling bone marrow, and myelogenous tissue is any tissue of, or arising from, bone marrow; in these senses the terms are usually used synonymously, as for example with chronic myeloid/myelogenous leukemia.
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated.
Monoblasts are the committed progenitor cells that differentiated from a committed macrophage or dendritic cell precursor (MDP) in the process of hematopoiesis. They are the first developmental stage in the monocyte series leading to a macrophage. Their myeloid cell fate is induced by the concentration of cytokines they are surrounded by during development. These cytokines induce the activation of transcription factors which push completion of the monoblast's myeloid cell fate. Monoblasts are normally found in bone marrow and do not appear in the normal peripheral blood. They mature into monocytes which, in turn, develop into macrophages. They then are seen as macrophages in the normal peripheral blood and many different tissues of the body. Macrophages can produce a variety of effector molecules that initiate local, systemic inflammatory responses. These monoblast differentiated cells are equipped to fight off foreign invaders using pattern recognition receptors to detect antigen as part of the innate immune response.
A promyelocyte is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte. Promyelocytes measure 12–20 microns in diameter. The nucleus of a promyelocyte is approximately the same size as a myeloblast but their cytoplasm is much more abundant. They also have less prominent nucleoli than myeloblasts and their chromatin is more coarse and clumped. The cytoplasm is basophilic and contains primary red/purple granules.
A metamyelocyte is a cell undergoing granulopoiesis, derived from a myelocyte, and leading to a band cell.
Granulopoiesis is a part of haematopoiesis, that leads to the production of granulocytes. A granulocyte, also referred to as a polymorphonuclear leukocyte (PMN), is a type of white blood cell that has multi lobed nuclei, usually containing three lobes, and has a significant amount of cytoplasmic granules within the cell. Granulopoiesis takes place in the bone marrow. It leads to the production of three types of mature granulocytes: neutrophils, eosinophils and basophils.
Acute myeloblastic leukemia with maturation (M2) is a subtype of acute myeloid leukemia (AML).
Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3, receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the FLT3 gene. FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III. CD135 is the receptor for the cytokine Flt3 ligand (FLT3L).
Homeobox protein Hox-A9 is a protein that in humans is encoded by the HOXA9 gene.
Acute basophilic leukemia is a rare form of acute myeloid leukemia where blasts are accompanied by abnormal basophils in all stages of differentiation. It would most likely be classified as M0 without electron microscopic confirmation of basophil lineage.
Mast cell leukemia is an extremely aggressive subtype of acute myeloid leukemia that usually occurs de novo but can, rarely, evolve from transformation of chronic myeloid leukemia into the more aggressive acute myeloid leukemia. In a small proportion of cases, acute mast cell leukemia may evolve from a more progressive form of systemic mastocytosis. The diagnosis of acute mast cell leukemia by the WHO criteria includes the requirement for a prevalence of 20% neoplastic mast cells in marrow and 10% in blood. If the mast cells represent less than 10% of blood cells, the tumor is called "aleukemic" mast cell leukemia.
In hematology, myelopoiesis in the broadest sense of the term is the production of bone marrow and of all cells that arise from it, namely, all blood cells. In a narrower sense, myelopoiesis also refers specifically to the regulated formation of myeloid leukocytes (myelocytes), including eosinophilic granulocytes, basophilic granulocytes, neutrophilic granulocytes, and monocytes.
CFU-GEMM is a colony forming unit that generates myeloid cells. CFU-GEMM cells are the oligopotential progenitor cells for myeloid cells; they are thus also called common myeloid progenitor cells or myeloid stem cells. "GEMM" stands for granulocyte, erythrocyte, monocyte, megakaryocyte.
AI-10-49 is a small molecule inhibitor of leukemic oncoprotein CBFβ-SMHHC developed by the laboratory of John Bushweller with efficacy demonstrated by the laboratories of Lucio H. Castilla and Monica Guzman. AI-10-49 allosterically binds to CBFβ-SMMHC and disrupts protein-protein interaction between CBFβ-SMMHC and tumor suppressor RUNX1. This inhibitor is under development as an anti-leukemic drug.