Human Megakaryoblastic Proliferation and Differentiation Events Observed by Phase-Contrast Cinematography

Boll, Irene; Domeyer, Cornelia; Bührer, Christoph

doi:10.1159/000203672

Cited by 8 publications

(7 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In these megakaryocytic cells, polyploidization (n = 58) occurs twice as often as cell doubling, mostly in steady-state enhancement. In acute idiopathic thrombocytopenic purpura (aITP) [16] and thrombocytosis mitotic cell doubling preponderates. One third of the tetraploid cells in the G 1 phase (n = 20) develop due to fusion of the daughter cells after termination of the cytokinesis because of their 25% larger cell circumferences.…”

Section: Resultsmentioning

confidence: 99%

“…In these cases the cells are called BFU E instead of myeloblasts [33]. As already mentioned, a number of disturbances during the course of mitosis in the progenitor cell line leads to the formation of polyploid cells (megakaryocytic cell line) although in aITP and thrombocytosis mitotic cell doubling preponderates [16,34]. The polyploidization-inducing lymphocytes show their close affiliation with the progenitor cell line.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Documentation of Normal and Leukemic Myelopoietic Progenitor Cells with High-Resolution Phase-Contrast Time-Lapse Cinematography

Boll¹

2001

Oncol Res Treat

View full text Add to dashboard Cite

The high-resolution phase-contrast, time-lapse cinematography using oil immersion lenses and 16-mm film demonstrates the kinetic cell events as maturation, locomotion, mitosis, and apoptosis of cells cultivated at 37 °C for up to 10 days. 0.5 v/v frozen-thawed sera with presumably high cytokine concentrations were added to the plasma or agar clot. Vital progenitor cells from human bone marrow and blood have a large, bright, unstructured nucleus with a large nucleolus and a narrow rim of cytoplasm (nuclear/cytoplasmic volume ratio = 0.7). Their nuclei are 6–14 µm in diameter and double their volume within 8 h. Many (70%) move at a mean speed of 2 µm/min, and many (30%) multiply with α-2α mitoses, generating progenitor cell families. Various disturbances during the course of mitosis lead to the formation of polyploid cells, thereby yielding the megakaryocytic cell line. Some of the progenitor cells undergo asymmetric α-αn mitoses: One of the two initially identical daughter cells remains a progenitor cell in the morphological sense, whereas the other daughter cell – depending on the size of its mother cell – matures in the same culture medium to form a granulocytopoietic, monocytopoietic or erythrocytopoietic cell line. – In acute myeloid leukemias (AML), the blasts and their nuclei are slightly larger than the corresponding progenitor cells and move faster (5 µm/min). Symmetric α-2α mitoses permit unlimited multiplication of the leukemic blasts if contact with cytotoxic lymphocytes does not render them apoptotic. This results in more stromal cells than normal. Granulocytopenia, monocytopenia, and anemia occur due to the genetic impairment of signaling control for asymmetric α-αn mitoses, and thrombocytopenia occurs due to the reduction in polyploidization.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Documentation of Normal and Leukemic Myelopoietic Progenitor Cells with High-Resolution Phase-Contrast Time-Lapse Cinematography

Boll¹

2001

Oncol Res Treat

View full text Add to dashboard Cite

show abstract

“…Megakaryocytes may contain other cells (most frequently polymorphonuclear leucocytes) in the cytoplasm as a result of emperipolesis, 26,27 a phenomenon in which cells enter the megakaryocyte cytoplasm and leave it after several hours. 28 To avoid contamination of microdissected megakaryocytes with other cells, we therefore selected only megakaryocytes that did not show emperipolesis, taking care to destroy their cytoplasm with the laser beam and to isolate only the nuclei. Paraffin samples from the 3 patients with NPMc ϩ AML used in this study showed cytoplasmic NPM in all leukemic cells of different lineages ( Figure 1C, top left); thus, the risk of isolating normal residual cells was negligible.…”

Section: Npm Mutation Analysis On Laser-microdissected Cellsmentioning

confidence: 99%

Mutated nucleophosmin detects clonal multilineage involvement in acute myeloid leukemia: impact on WHO classification

Pasqualucci¹,

Liso²,

Martelli³

et al. 2006

Blood

View full text Add to dashboard Cite

Because of a lack of specific clonality markers, information on lineage involvement and cell of origin of acute myeloid leukemia with normal karyotype (AML-NK), is missing. Because Nucleophosmin (NPM) gene is frequently mutated in AML-NK and causes aberrant NPM cytoplasmic localization (NPMc ؉ ), it was used as an AML lineage clonality marker. Clonal NPM exon 12 mutations were detected in myeloid, monocytic, erythroid, and megakaryocytic cells but not in fibroblasts or endothelia that were lasermicrodissected from 3 patients with NPMc ؉ AML. Aberrant cytoplasmic expression of mutated NPM proteins was identified with anti-NPM antibodies in 2 or more myeloid hemopoietic cell lineages in 99 (61.5%) of 161 of NPMc ؉ AML paraffin-embedded bone marrow biopsies; lymphoid involvement was excluded in 3 investigated cases. These findings suggest that NPMc ؉ AML derives from either a common myeloid or earlier progenitor. IntroductionClonal cell lineage involvement in myelodysplastic syndrome and acute myeloid leukemia (AML) carrying recurrent genetic abnormalities can be successfully investigated by a number of techniques, including cytogenetics, fluorescence in situ hybridization (FISH), FISH combined with immunophenotyping, and polymerase chain reaction (PCR) on purified cell populations, which are all able to detect leukemia-specific molecular alterations. 1-7 Unfortunately, no specific genetic markers are as yet available for a significant proportion of AML. Under these circumstances, cell lineage clonality can be investigated by analysis of X-chromosome inactivation patterns, 8 but this technique has not been applied widely to AML. Thus, no or scarce information is available on cell lineage involvement or cell of origin in most AMLs, especially those with normal karyotype (AML-NK), 9 which lack specific clonality markers and account for 40% to 50% of de novo adult AML. 10 All genetically poorly defined AMLs, including AML-NK, are now included into the category of "acute myeloid leukemia not otherwise characterized" of the World Health Organization (WHO) classification. 11 This large, poorly characterized subgroup of AML is currently defined according to criteria of the French-AmericanBritish (FAB) classification 12 (with some modification), which is based on morphologic and cytochemical features of the leukemic cells and degree of maturation. Given its frequency and extreme heterogeneity, AML not otherwise characterized clearly needs to be defined better.We recently identified mutations of the NPM gene exon 12 as the most common and specific genetic lesion associated with AML-NK, 13 being observed in 50% to 60% of cases, as confirmed to date in more than 3500 patients with AML. [14][15][16][17][18][19] At the NPM protein C-terminus, these mutations modify critical tryptophan(s) and create a new nuclear export signal (NES) motif, which act together to aberrantly localize NPM leukemic mutants in the cytoplasm 20,21 -hence the term NPMc ϩ (cytoplasmic-positive) AML. 13 As the NPM mutant protein dislocates the NPM wild-t...

show abstract

“…Exposure of BM to severe stress with Bz may have resulted in releasing platelet stem cells into the circulation, reaching the spleen for subsequent proliferation and differentiation ( 37 ). Also, Bz affected the spleen structure and organization, leading to the accumulation of megakaryocytes, as the spleen became unable to function as an alternate hematopoietic organ with platelets, liberation was impaired, and megakaryocytes accumulated in the spleen ( 38 ). Previous studies ( 39 , 40 ) mentioned that hematopoiesis occurs outside the BM, including the spleen and liver, as a result of pathophysiological alterations in hematopoietic stem/progenitor cells, as well as the ectopic emergence of their niche in these tissues, a process called EMH.…”

Section: Discussionmentioning

confidence: 99%

Ameliorative Effects of Bovine Lactoferrin on Benzene-Induced Hematotoxicity in Albino Rats

et al. 2022

View full text Add to dashboard Cite

Benzene (Bz) is one of the major products of the petrochemical industry globally, which induces aplastic anemia and leukemia in humans and animals. This study aimed to investigate the modulatory effects of bovine lactoferrin (bLf) on Bz-induced hematotoxicity in albino rats. Eighty male rats were randomly divided into eight groups: corn oil group [2 mL/kg body weight (BW)], bLf groups (100, 200, and 300 mg/kg BW), Bz group (Bz 2 mL/kg BW; corn oil 2 mL/kg BW), and Bz + bLf groups (Bz 2 mL/kg BW; corn oil 2 mL/kg BW; bLf 100, 200, and 300 mg/kg BW). Hematobiochemical results exhibited marked pancytopenia, a significant decrease in total protein, albumin, α2- and γ-globulin, ferritin, serum iron, and total iron-binding capacity (TIBC), and an increase in serum bioactivities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and erythropoietin hormone levels in Bz-treated rats. Histopathological examination revealed a marked reduction in all hematopoietic cell lines in the bone marrow (BM), necrosis in the white pulp of the spleen and cytosolic hydrops, and apoptosis of hepatocytes in the Bz-treated group. Rats treated with bLf (300 mg/kg BW) revealed marked increases in total protein, albumin, α2- and γ-globulin, ferritin, serum iron, and TIBC levels and decreases both in ALP and LDH bioactivities and erythropoietin hormone levels compared with the Bz-treated group. Histopathological results were concomitant with hematobiochemical parameters in rats treated with bLf (300 mg/kg BW), almost showing restoration of the normal cellularity of BM, the architecture of red and white pulps of the spleen, and even the normal hypertrophy of hepatocytes compared with the control groups. To conclude, bLf (300 mg/kg BW) can be recommended to treat Bz-induced hematotoxicity.

show abstract

Human Megakaryoblastic Proliferation and Differentiation Events Observed by Phase-Contrast Cinematography

Cited by 8 publications

References 7 publications

Documentation of Normal and Leukemic Myelopoietic Progenitor Cells with High-Resolution Phase-Contrast Time-Lapse Cinematography

Documentation of Normal and Leukemic Myelopoietic Progenitor Cells with High-Resolution Phase-Contrast Time-Lapse Cinematography

Mutated nucleophosmin detects clonal multilineage involvement in acute myeloid leukemia: impact on WHO classification

Ameliorative Effects of Bovine Lactoferrin on Benzene-Induced Hematotoxicity in Albino Rats

Contact Info

Product

Resources

About