scholarly journals The Cell Body Space Occupied by the Nucleus During the Cell Differentiation in Human Lymphocytic, Granulocytic and Erythroid Cell Lineages

2021 ◽  
pp. 701-707
Author(s):  
K SMETANA ◽  
H KLAMOVÁ ◽  
D MIKULENKOVÁ ◽  
J ČERMÁK ◽  
P OTEVŘELOVÁ ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Cell Body ◽  
Myeloid Leukemia ◽  
Cell Lineage ◽  
Lymphocytic Leukemia ◽  
Erythroid Cell ◽  
Refractory Anemia ◽  
Specific Cell ◽  
Cell Lineages ◽  
Lymphocytic Cell

The present nuclear and cell body diameter measurements demonstrated size differences of the approximate cell space estimate occupied by the cell nucleus during the cell differentiation in lymphocytic, granulocytic and erythroid cell lineages. These lineages were used as convenient models because all differentiation steps were easily identified and accessible in diagnostic peripheral blood or bone marrow smears of blood donors (BDs), patients suffering from chronic lymphocytic leukemia (CLL), patients with chronic myeloid leukemia (CML) and refractory anemia (RA) of the myelodysplastic syndrome (MDS). The cell space occupied by the nucleus was constant and did not change during the cell differentiation in the lymphocytic cell lineages of BDs and CLL patients despite the decreased cell size. In contrary, the cell space occupied by the nucleus markedly decreased in differentiating cells of granulocytic and erythroid lineages of patients suffering from CML. In the erythroid cell lineage in patients with RA of MDS the small reduction of the cell space occupied by the nucleus during the differentiation was not significant. The measurements also indicated that in progenitor cells of all studied cell lineages nuclei occupied more than 70 % of the cell space. Thus, the nucleus-cytoplasmic morphological and functional equilibrium appeared to be characteristic for each differentiation step and each specific cell lineage.

scholarly journals Knockout of both miR-15/16 loci induces acute myeloid leukemia

2018 ◽  
Vol 115 (51) ◽  
pp. 13069-13074 ◽  
Author(s):  
Francesca Lovat ◽  
Matteo Fassan ◽  
Diana Sacchi ◽  
Parvathi Ranganathan ◽  
Alexey Palamarchuk ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Myeloproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Wild Type ◽  
Double Positive ◽  
Cell Lineages ◽  
Chromosome 13Q14 ◽  
Complete Deletion

MicroRNAs (miRNAs) have been extensively reported to be associated with hematological malignancies. The loss of miR-15a/16–1 at chromosome 13q14 is a hallmark of most of human chronic lymphocytic leukemia (CLL). Deletion of murine miR-15a/16–1 and miR-15b/16–2 has been demonstrated to promote B cell malignancies. Here, we evaluate the biological role of miR-15/16 clusters, crossbreeding miR-15a/16–1 and miR-15b/16–2 knockout mice. Unexpectedly, the complete deletion of both clusters promoted myeloproliferative disorders in the majority of the mice by the age of 5 months with a penetrance of 70%. These mice showed a significant enlargement of spleen and abnormal swelling of lymph nodes. Flow cytometry characterization demonstrated an expanded CD11b/Gr-1 double-positive myeloid population both in spleen and in bone marrow. The transplantation of splenocytes harvested from double-KO mice into wild-type recipient mice resulted in the development of myeloproliferative disorders, as observed in the donors. In vivo, miR-15/16 cluster deletion up-regulated the expression of Cyclin D1, Cyclin D2, and Bcl-2. Taken together, our findings identify a driver oncogenic role for miR-15/16 cluster deletion in different leukocytic cell lineages.

scholarly journals Jiyuan Oridonin A Overcomes Differentiation Blockade in Acute Myeloid Leukemia Cells With MLL Rearrangements via Multiple Signaling Pathways

2021 ◽  
Vol 11 ◽  
Author(s):  
Mei Qu ◽  
Yu Duan ◽  
Min Zhao ◽  
Zhanju Wang ◽  
Mengjie Zhao ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Differentiation ◽  
Cell Line ◽  
Myeloid Leukemia ◽  
Cell Lineage ◽  
Differentiation Therapy ◽  
Proliferative Effect ◽  
Acute Myeloid Leukemia Cells ◽  
Colony Forming Capacity ◽  
Acute Myeloid

Differentiation therapy with all-trans-retinoic acid (ATRA) in acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML), has been extremely successful in inducing clinical remission in APL patients. However, the differentiation therapy of ATRA-based treatment has not been effective in other subtypes of AML. In this study, we evaluated a small molecule of ent-kaurene diterpenoid, Jiyuan oridonin A (JOA), on the differentiation blockade in AML cells with the mixed lineage leukemia (MLL) gene rearrangements (MLLr) in MV4-11, MOLM-13 and THP-1 cells. We found that JOA could significantly inhibit the proliferation of MOLM-13, MV4-11 and THP-1 cells. Moreover, JOA promoted cell differentiation coupled with cell-cycle exit at G0/G1 and inhibited the colony- forming capacity of these cells. We showed that the anti-proliferative effect of JOA attributed to cell differentiation is most likely through the martens tretinoin response up pathway in the MOLM-13 cell line, and the hematopoietic cell lineage pathway by the inhibition of c-KIT expression and cell adhesion pathway in the THP-1 cell line. Our findings suggest that JOA could be a novel therapeutic agent against human MLLr acute myeloid leukemia.

scholarly journals Multidimensional Chromatin Regulation of Cell Lineage Differentiation in a Metazoan Embryo

2020 ◽  
Author(s):  
Zhiguang Zhao ◽  
Rong Fan ◽  
Weina Xu ◽  
Yangyang Wang ◽  
Xuehua Ma ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Single Cell Analysis ◽  
Cell Lineage ◽  
Specific Cell ◽  
Chromatin Regulation ◽  
Chromatin Dynamics ◽  
Critical Dimensions ◽  
C Elegans ◽  
Lineage Differentiation

SUMMARYHow chromatin dictates cell differentiation is an intriguing question in developmental biology. Here, a reporter gene integrated throughout the genome was used as a sensor to map the chromatin activity landscape in lineage-resolved cells during C. elegans embryogenesis. Single-cell analysis of chromatin dynamics across critical dimensions of cell differentiation was performed, including lineage, tissue, and symmetry. During lineage progression, chromatin gradually diversifies in general and exhibits switch-like changes following specific cell division, which is predictive of anterior-posterior fate asymmetry. Upon tissue differentiation, chromatin of cells from distinct lineages converge to tissue-specific states but retain “memory” of each cell’s lineage history, which contributes to intra-tissue heterogeneity. However, cells with a morphologically left-right symmetric organization utilize a predetermination chromatin strategy to program analogous regulatory states in early progenitor cells. Additionally, chromatin co-regulation drives the functional coordination of the genome. Collectively, this work reveals the role of multidimensional chromatin regulation in cell differentiation.

scholarly journals Maintenance of telomere length in AML

2017 ◽  
Vol 1 (25) ◽  
pp. 2467-2472 ◽  
Author(s):  
Peter M. Lansdorp
Keyword(s):  
Disease Progression ◽  
Telomere Length ◽  
Myeloid Leukemia ◽  
Bone Marrow Failure ◽  
Point Mutations ◽  
Chronic Phase ◽  
Telomerase Activity ◽  
Lymphocytic Leukemia ◽  
Specific Cell ◽  
Telomere Biology

Abstract The importance of telomere length to human health, aging, and cancer continues to be underappreciated. This review examines some basics of telomere biology and relates how telomere function, telomerase activity, and mutations in TERC or TERT are involved in bone marrow failure, leukemias, and other cancers. Given the challenge to obtain accurate data on telomerase activity and telomere length in specific cell types, the situation in acute myeloid leukemia (AML) remains puzzling. In most cancers, telomerase levels are increased after cells have encountered a “telomere crisis,” which is typically associated with poor prognosis. Cells emerging from “telomere crisis” have defective DNA damage responses, resulting, for example, from loss of p53. Such cells often express elevated telomerase levels as a result of point mutations in the TERT promoter or amplification of the TERT gene. While telomeres in AML blasts are typically shorter than expected for normal leukocytes, most AML cells do not show evidence of having gone through a “telomere crisis.” In chronic myeloid leukemia (CML), the difference between the telomere length in nonmalignant T cells and malignant blasts from the same patient was found to correlate with the remaining duration of the chronic phase. This observation supports that a mitotic clock is ticking in CML stem cells and that disease progression in CML heralds the onset of a “telomere crisis.” The presence of very short telomeres in tumor cells was found to predict disease progression in chronic lymphocytic leukemia, myeloma, and various solid tumors. In view of these findings longitudinal studies of telomere length in AML appear worthwhile.

scholarly journals Inherited bone marrow failure syndromes. An overview

2021 ◽  
Vol 11 (1) ◽  
pp. 1873-1880
Author(s):  
Shovana Karki
Keyword(s):  
Bone Marrow ◽  
Blood Cell ◽  
Viral Infections ◽  
Clinical Symptoms ◽  
Bone Marrow Failure ◽  
Cell Lineage ◽  
Dyskeratosis Congenita ◽  
Lymphocytic Leukemia ◽  
Cell Lineages ◽  
Bone Marrow Failure Syndromes

Inherited bone marrow failure syndromes are a diverse set of genetic disorders characterized by insufficient blood cell production leading to cytopenias/pancytopenia. Bone marrow failure can be restricted to one or two blood cell lineages, with symptoms specific to the particular cell lineage or it can affect all cell lineages, causing clinical symptoms similar to aplastic anemia. Inherited bone marrow failure syndromes are genetically heterogeneous diseases resulting from germline mutations that affect key cellular pathways namely ribosomal biogenesis, telomerase biology, DNA repair, and structural proteins. Common Inherited bone marrow failure syndromes are Diamond-Blackfan anemia, Fanconi anemia, Dyskeratosis Congenita, and Shwachman-Diamond syndrome. These different syndromes have variable prognoses and risks of developing hematological or solid malignancies. Thus the accurate diagnosis of these diseases differentiating it from other Inherited bone marrow failure syndromes and other causes of bone marrow failure is of utmost importance for management and surveillance of long-term squeal of the disease. Other causes of BMF can be acquired. The most common forms of Bone marrow failure can occur from chemicals, radiation, drugs, viral infections, immune disorders, myelodysplastic syndrome, paroxysmal nocturnal hemoglobinuria, or large granular lymphocytic leukemia. Moreover, these Inherited bone marrow failure syndromes are often heritable, affecting other family members, thus requiring insightful genetic counseling. This review discusses the frequent Inherited bone marrow failure syndromes along with their differential diagnosis.

scholarly journals Changes in globin messenger RNA content during erythroid cell differentiation.

1975 ◽  
Vol 250 (15) ◽  
pp. 6054-6058
Author(s):  
F Ramirez ◽  
R Gambino ◽  
G M Maniatis ◽  
R A Rifkind ◽  
P A Marks ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Messenger Rna ◽  
Erythroid Cell ◽  
Rna Content ◽  
Erythroid Cell Differentiation

scholarly journals RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3192
Author(s):  
Antoine Gleizes ◽  
Mouna Triki ◽  
Sandrine Bonnet ◽  
Naomi Baccari ◽  
Gabriel Jimenez-Dominguez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Differentiation ◽  
Paneth Cell ◽  
Wnt Signaling Pathway ◽  
Cell Lineage ◽  
Human Colon ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Sox9 Expression ◽  
Human Colon Cancer

RIP140 is a major transcriptional coregulator of gut homeostasis and tumorigenesis through the regulation of Wnt/APC signaling. Here, we investigated the effect of RIP140 on Paneth cell differentiation and its interplay with the transcription factor SOX9. Using loss of function mouse models, human colon cancer cells, and tumor microarray data sets we evaluated the role of RIP140 in SOX9 expression and activity using RT-qPCR, immunohistochemistry, luciferase reporter assays, and GST-pull down. We first evidence that RIP140 strongly represses the Paneth cell lineage in the intestinal epithelium cells by inhibiting Sox9 expression. We then demonstrate that RIP140 interacts with SOX9 and inhibits its transcriptional activity. Our results reveal that the Wnt signaling pathway exerts an opposite regulation on SOX9 and RIP140. Finally, the levels of expression of RIP140 and SOX9 exhibit a reverse response and prognosis value in human colorectal cancer biopsies. This work highlights an intimate transcriptional cross-talk between RIP140 and SOX9 in intestinal physiopathology.

scholarly journals Aspects of the biology of regeneration and repair in the human gastrointestinal tract

1998 ◽  
Vol 353 (1370) ◽  
pp. 925-933 ◽  
Author(s):  
Nicholas A. Wright
Keyword(s):  
Stem Cells ◽  
Gastric Gland ◽  
Cell Lineage ◽  
Mucosal Ulceration ◽  
Cell Lineages ◽  
Trefoil Peptides ◽  
Pyloric Mucosa ◽  
A Cell ◽  
Epidermal Growth ◽  
Altered Gene

The main pathways of epithelial differentiation in the intestine, Paneth, mucous, endocrine and columnar cell lineages are well recognized. However, in abnormal circumstances, for example in mucosal ulceration, a cell lineage with features distinct from these emerges, which has often been dismissed in the past as ‘pyloric’ metaplasia, because of its morphological resemblance to the pyloric mucosa in the stomach. However, we can conclude that this cell lineage has a defined phenotype unique in gastrointestinal epithelia, has a histogenesis that resembles that of Brunner's glands, but acquires a proliferative organization similar to that of the gastric gland. It expresses several peptides of particular interest, including epidermal growth factor, the trefoil peptides TFF1, TFF2, TFF3, lysozyme and PSTI. The presence of this lineage also appears to cause altered gene expression in adjacent indigenous cell lineages. We propose that this cell lineage is induced in gastrointestinal stem cells as a result of chronic mucosal ulceration, and plays an important part in ulcer healing; it should therefore be added to the repertoire of gastrointestinal stem cells.

scholarly journals Not BCL2 mutation but dominant mutation conversation contributed to acquired venetoclax resistance in acute myeloid leukemia

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Xiang Zhang ◽  
Jiejing Qian ◽  
Huafeng Wang ◽  
Yungui Wang ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Underlying Mechanism ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Dominant Mutation ◽  
First Line Therapy ◽  
Line Therapy ◽  
Acute Myeloid

AbstractVenetoclax (VEN) plus azacitidine has become the first-line therapy for elderly patients with acute myeloid leukemia (AML), and has a complete remission (CR) plus CR with incomplete recovery of hemogram rate of ≥70%. However, the 3-year survival rate of these patients is < 40% due to relapse caused by acquired VEN resistance, and this remains the greatest obstacle for the maintenance of long-term remission in VEN-sensitive patients. The underlying mechanism of acquired VEN resistance in AML remains largely unknown. Therefore, in the current study, nine AML patients with acquired VEN resistance were retrospectively analyzed. Our results showed that the known VEN resistance-associated BCL2 mutation was not present in our cohort, indicating that, in contrast to chronic lymphocytic leukemia, this BCL2 mutation is dispensable for acquired VEN resistance in AML. Instead, we found that reconstructed existing mutations, especially dominant mutation conversion (e.g., expanded FLT3-ITD), rather than newly emerged mutations (e.g., TP53 mutation), mainly contributed to VEN resistance in AML. According to our results, the combination of precise mutational monitoring and advanced interventions with targeted therapy or chemotherapy are potential strategies to prevent and even overcome acquired VEN resistance in AML.

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