Myeloblastic cells

TUMOR NECROSIS FACTOR ALPHA STIMULATES THE GROWTH OF THE CLONOGENIC CELLS OF ACUTE MYELOBLASTIC LEUKEMIA IN SYNERGY WITH GRANULOCYTE / MACROPHAGE COLONY -STIMULATING FACTOR... 

AML represents a group of disorders in which both failure to differentiate and overproliferation in the stem cell compartment produce an overabundance of nonfunctional cells termed myeloblasts. While the specific cause for this biologic abnormality is unknown, an understanding of the genetic influence of leukemia is leading to a wide variety of targeted therapies.9... 

The stages of neutrophil development have been extensively and elegantly described by Dorothy Bainton (1980). The earliest identifiable cells of the neutrophil lineage are the myeloblasts, and the developmental stages are shown in Figure 2.4. 

Identification of these cell types is based on the morphological analysis of cells, staining for peroxidase and analysis by light and electron microscopy. Of every 100 nucleated cells in the marrow, 2 are myeloblasts, 5 are promyelocytes, 12 are myelocytes, 22 are metamyelocytes and band cells and 20 are mature neutrophils. These values are somewhat variable and may differ between individuals. Thus, about 60% of all marrow cells are of the neutrophil lineage. 

These cells are relatively undifferentiated and have a large nucleus, distinguishable nucleolus but few, if any, cytoplasmic granules. Myeloblasts arise from a precursor pool of stem cells, and both the rough endoplasmic reticulum and the Golgi apparatus stain for peroxidase, indicating that this enzyme is beginning to be synthesised. This cell type is capable of proliferation. 

Chuang LF, Hinton DE, Cheung ATW, et al. 1991. Induction of differentiation in human myeloblastic leukemia ML-1 cells by heptachlor, a chlorinated hydrocarbon insecticide. Toxicol AppI Pharmacol 109 98-107. 

Numerous case reports and epidemiological studies suggest a leukemogenic action of benzene in humans—the leukemia tending to be acute and myeloblastic in type, often following aplastic changes in the bone marrow. Acute myelocytic leukemia may be preceded by myelodysplastic syndrome, a preleukemic state characterized by abnormal marrow architecture, inadequate hematopoiesis, and many cells with chromosome damage." Benzene may also induce chronic types of leukemia. ... 

Arylamino-substituted-pyrrolo[2,3-3]pyridines, synthesized via 4-chloropyrrolo[2,3-/ ]pyridine, have been evaluated for their biological properties on human myeloblastic leukemia cells <2007BML1934>. 

On the other hand, hydroquinone (3 pmol/L) prevented the staurosporine-induced apoptosis of HL-60 and the IL-3-dependent murine myeloblastic (32D) cell line it also prevented apoptosis of the 32D cells observed in the absence of IL-3. The myeloperoxidase inhibitor indomethacin opposed the effect of hydroquinone on staurosporine-induced apoptosis of HL-60 cells (Hazel et al., 1995, 1996b). Pretreatment of human leukaemia cells ML-1 with buthionine sulfoximine (100 pmol/L for 24 h), in order to decrease their glutathione content, increased the susceptibility of these cells to hydroquinone-induced inhibition of differentiation caused by phorbol acetate pretreatment with l,2-dithiole-3-thione, which induces reduced glutathione synthesis, prevented the differentiation inhibition of hydroquinone. Treatment of DBA/2 mice with 1,2-dithiole-3-thione, which increased the activity of quinone reductase of bone-marrow stromal cells by 50%, decreased the susceptibility of these cells towards hydroquinone (Trush et al., 1996). 

Hazel, B.A., O Connor, A., Niculescu, R. Kalf, GF. (1995) Benzene and its metabolite, hydroquinone, induce granulocytic differentiation in myeloblasts by interacting with cellular signaling pathways activated by granulocyte colony-stimulating factor. Stem Cells, 13, 295-310... 

Hazel, B.A., Baum, C. Kalf, GF. (1996b) Hydroquinone, a bioreactive metabolite of benzene, inhibits apoptosis in myeloblasts. Stem Cells, 14, 730-742... 

Fig. 6.15. Bone marrow from a normal donor showing CD45/SSC clusters. CD45 expression varies as cells mature. Lymph = lymphocytes Mono = monocytes L-Blast = lymphoblasts M-Blast = myeloblasts Myeloid = neutrophils and Erythroid = cells of the erythroid lineage. From Loken and Wells (2000).

Hematological Effects. Severe leukocytosis, with notable increases in immature polymorphonuclear cells, myelocytes, and myeloblasts and nucleated red cells and Howell-Jolly bodies, indicative of hemolytic anemia were observed in individuals after application of a salve that contained potassium chromate to treat scabies (Brieger 1920). Leukocytosis was also described in a case report of a man who was admitted to a hospital with skin ulcers on both hands due to dermal exposure to ammonium dichromate in a planographic printing establishment, where he had worked for a few months (Smith 1931). It should be noted that the man had a history of asthma. 

Xu B, Wilson BA, Lu L (1996) Induction of human myeloblastic ML-1 cell G1 arrest by suppression of K+ channel activity. Am J Physiol Cell Physiol 40 C2037-C2044... 

Xu DZ, Wang L, Dai W, Lu L (1999) A requirement for K+-channel activity in growth factor-mediated extracellular signal-regulated kinase activation in human myeloblastic leukemia ML-1 cells. Blood 94 139-145... 

Aplastic anemia is a more severe effect of benzene and occurs when the bone marrow ceases to function and the stem cells never reach maturity. Depression in bone marrow function occurs in two stages—hyperplasia (increased synthesis of blood cell elements), followed by hypoplasia (decreased synthesis). As the disease progresses, bone marrow function decreases and the bone marrow becomes necrotic and filled with fatty tissue. This myeloblastic dysplasia without acute leukemia has been seen in persons exposed to benzene. Aplastic anemia can progress to a type of leukemia known as acute myelogenous leukemia (Aksoy 1980), which is discussed in Section 2.2.1.8. 

Life-threatening splenic mpture occnrred in a 22-year-old woman with acnte myeloid lenkemia (53). The rupture was diagnosed in the presence of abdominal pain and signs of hypovolemic shock, 10 days after she started G-CSF treatment to support peripheral blood stem cell transplantation. Histology after splenectomy showed only small clnsters of myeloblasts and no specific cause for the mpture. In particnlar, she was still pancytopenic at the time of splenic mpture. 

Katayama Y, Deguchi S, Shinagawa K, Teshima T, Notohara K, Taguchi K, Omoto E, Harada M. Bone marrow necrosis in a patient with acute myeloblastic leukemia during administration of G-CSF and rapid hematologic recovery after allotransplantation of peripheral blood stem cells. Am J Hematol 1998 57(3) 238 0. 

IL-9 can support cell proliferation in the absence of an antigen or APC, Overproduction of it may lead to T-cell tumors, particularly of Th2 lymphocytes. In certain lymphomas, such as Hodgkin s lymphoma, it may act as an autocrine signal for cellular proliferation. IL-9 may play a role in the development of acute myeloblastic leukemia by stimulating leukemic cells to enter the S-phase rather than preventing cell death. In addition, IL-9 acts synergisticaUy with stem cell factor for recruitmg quiescent leukemic cells in the cell cycle. ... 

Cheng GY, Minden MD, Toyonaga B, Mak TW, McCulloch EA. T cell receptor and immunoglobulin gene rearrangements in acute myeloblastic leukemia. 

Finally, there is evidence that cannabidiol can induce apoptosis in cultures of at least some types of human cancer cell HL-60 myeloblastic leukaemia cells and... 

Gallily R, Even-Chen T, Katzavian G, Lehmann D, Dagan A, Mechoulam R (2003) y-Irradiation enhances apoptosis induced by cannabidiol, a non-psychotropic cannabinoid, in cultured HL-60 myeloblastic leukemia cells. Leuk Lymphoma 44 1767-1773... 

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