scholarly journals Acute Myeloid and Lymphoblastic Leukemia Cell Interactions with Endothelial Selectins: Critical Role of PSGL-1, CD44 and CD43

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1253 ◽  
Author(s):  
Caroline Spertini ◽  
Bénédicte Baïsse ◽  
Marta Bellone ◽  
Milica Gikic ◽  
Tatiana Smirnova ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Vascular Endothelium ◽  
Lymphoblastic Leukemia ◽  
Critical Role ◽  
Leukemia Cell ◽  
Hematologic Malignancies ◽  
Selectin Ligands ◽  
Blast Cells ◽  
Acute Myeloid

Acute myeloid and lymphoblastic leukemia are poor prognosis hematologic malignancies, which disseminate from the bone marrow into the blood. Blast interactions with selectins expressed by vascular endothelium promote the development of drug resistance and leukostasis. While the role of selectins in initiating leukemia blast adhesion is established, our knowledge of the involved selectin ligands is incomplete. Using various primary acute leukemia cells and U937 monoblasts, we identified here functional selectin ligands expressed by myeloblasts and lymphoblasts by performing biochemical studies, expression inhibition by RNA interference and flow adhesion assays on recombinant selectins or selectin ligands immunoadsorbed from primary blast cells. Results demonstrate that P-selectin glycoprotein ligand-1 (PSGL-1) is the major P-selectin ligand on myeloblasts, while it is much less frequently expressed and used by lymphoblasts to interact with endothelial selectins. To roll on E-selectin, myeloblasts use PSGL-1, CD44, and CD43 to various extents and the contribution of these ligands varies strongly among patients. In contrast, the interactions of PSGL-1-deficient lymphoblasts with E-selectin are mainly supported by CD43 and/or CD44. By identifying key selectin ligands expressed by acute leukemia blasts, this study offers novel insight into their involvement in mediating acute leukemia cell adhesion with vascular endothelium and may identify novel therapeutic targets.

Tribbles in acute leukemia

Blood ◽  
2013 ◽  
Vol 121 (21) ◽  
pp. 4265-4270 ◽  
Author(s):  
Kai Ling Liang ◽  
Loveena Rishi ◽  
Karen Keeshan
Keyword(s):  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Therapeutic Strategies ◽  
Acute Leukemias ◽  
Hematopoietic Malignancies ◽  
Novel Therapeutic Strategies ◽  
Acute Myeloid ◽  
Novel Therapeutic

Abstract There is growing research interest in the mammalian Tribbles (Trib) family of serine/threonine pseudokinases and their oncogenic association with acute leukemias. This review is to understand the role of Trib genes in hematopoietic malignancies and their potential as targets for novel therapeutic strategies in acute myeloid leukemia and acute lymphoblastic leukemia. We discuss the role of Tribs as central signaling mediators in different subtypes of acute leukemia and propose that inhibition of dysregulated Trib signaling may be therapeutically beneficial.

MicroRNA Expression Signatures Accurately Discriminate Acute Lymphoblastic Leukemia from Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 231-231
Author(s):  
Shuangli Mi ◽  
Jun Lu ◽  
Miao Sun ◽  
Zejuan Li ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Acute Leukemias ◽  
In Vivo Models ◽  
Acute Myeloid

Abstract Human acute leukemias include acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). It is estimated that 5,200 and 13,410 cases will be diagnosed with and 1,420 and 8,990 will die of ALL and AML, respectively, in the United States in 2007. Although remarkable progress has been made in the past decades in the treatment and in the understanding of the biology of acute leukemias, the 5-year overall survival rate of patients with AML is only approximately 22%, which is much lower than that of ALL patients (65%; http://seer.cancer.gov). One of the most exciting recent findings is the discovery of an abundant class of small (∼22 nt), non-(protein-)coding RNAs, called microRNAs (miRNAs, miRs), which can function as oncogenes and tumor suppressors, whose deregulation is clearly associated with the development of cancer. To understand the distinct mechanisms in leukemogenesis between ALL and AML and to identify novel markers for diagnosis and treatment of acute leukemia, we have performed a large-scale miRNA expression profiling assay with a bead-based flow cytometric method and identified 27 differentially expressed miRNAs. Among them, miR-128a and b are significantly overexpressed while let-7b and miR-223 are significantly down-regulated in ALL compared to AML. They are the most discriminatory miRNAs between ALL and AML. Using the expression signatures of any two of the four most significantly discriminatory miRNAs in diagnosis of ALL and AML resulted in an accuracy rate of 97–100%. The differential expression patterns of these four miRNAs were validated further through quantitative real-time PCR on 98 acute leukemia samples covering most of the common cytogenetic subtypes of AML and B- and T-cell ALL, along with 10 normal controls. Furthermore, we found that overexpression of miR-128a and b in ALL was at least partly associated with hypomethylation, rather than amplification of DNA locus copy. Moreover, several important target genes of these four miRNAs have also been validated. We are currently exploring the role of these four miRNAs and their critical target genes in leukemogenesis and in the determination of lineage fate during leukemia development using in vitro and in vivo models. This work will enhance our understanding of the biological role of these miRNAs and their targets in leukemogenesis, and in determining the lineage fate of acute leukemia.

AKT inhibitor, GSK690693, induces growth inhibition and apoptosis in acute lymphoblastic leukemia cell lines

Blood ◽  
2009 ◽  
Vol 113 (8) ◽  
pp. 1723-1729 ◽  
Author(s):  
Dana S. Levy ◽  
Jason A. Kahana ◽  
Rakesh Kumar
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cell Lines ◽  
Kinase Inhibitor ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Hematologic Malignancies ◽  
Akt Signaling ◽  
Akt Inhibitor ◽  
Akt Kinase

Abstract The PI3K/AKT signaling is activated in various hematologic malignancies. We evaluated the effect of a novel, pan-AKT kinase inhibitor, GSK690693, on the proliferation of 112 cell lines representing different hematologic neoplasia. Fifty-five percent of all cell lines tested were sensitive to AKT inhibitor (EC50 < 1 μM), with acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma, and Burkitt lymphoma showing 89%, 73%, and 67% sensitivity to GSK690693, respectively. The antiproliferative effect was selective for the malignant cells, as GSK690693 did not inhibit the proliferation of normal human CD4+ peripheral T lymphocytes as well as mouse thymocytes. Phosphorylation of downstream substrates of AKT was reduced in both sensitive and insensitive cell lines on treatment with GSK690693, suggesting that the cause of resistance was not related to the lack of AKT kinase inhibition. Consistent with the role of AKT in cell survival, GSK690693 also induced apoptosis in sensitive ALL cell lines. Overall, our data provide direct evidence for the role of AKT signaling in various hematologic malignancies, especially ALL and some lymphomas.

scholarly journals Evaluation of seasonal changes in the diagnosis of acute leukemia in Turkey

2020 ◽  
Vol 7 (5) ◽  
pp. 501-504
Author(s):  
Tuğçe Nur Yiğenoğlu ◽  
Derya Şahin ◽  
Semih Başcı ◽  
Mehmet Bakırtaş ◽  
Tahir Darçın ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Leukemia ◽  
Seasonal Changes ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Critical Role ◽  
Number Of Patients ◽  
The Relationship ◽  
Acute Myeloid

Objective: The etiology of acute leukemia (AL) has been under investigation for decades but the exact cause is still unknown. There are studies suggesting that infection plays a critical role in the development of AL in conjunction with other risk factors. In some studies, it has been shown that the incidence of AL increases after influenza endemics. This shows that viruses may play a role in the etiology. The theory that viruses might have a role in the etiopathogenesis created the idea that AL frequency may peak during some specific months; therefore, in this study, we aimed to research the relationship between AL diagnosis frequency and seasons in Turkey.  Method: 186 patients who were diagnosed with de novo acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) diagnosis at our center were included in the study. Results: The frequency of ALL diagnoses were as follows:  25 (34.3%) in winter, 19 (26%) in spring, 15 (20.5%) in autumn, and 14 (19.2%) in summer. The frequency of AML diagnose was as follows:   24 (21.2%) in winter, 30 (26.6%) in spring, 27 (23.8%) in autumn and 32 (28.4%) in summer. In our study, we did not find a statistically significant relationship between AL diagnosis frequency and seasons. Conclusion: According to our literature review, there are two studies including our study, searching for a relationship between AL diagnosis frequency and seasons in Turkey. Neither of the studies found a relationship between AL and seasons. According to our analysis the numbers of the patient in studies are limited; therefore the studies with high number of patients are needed to find out a relation between seasons and diagnosis time of AL.

scholarly journals Pre-Clinical Evaluation of the Proteasome Inhibitor Ixazomib against Bortezomib-Resistant Leukemia Cells and Primary Acute Leukemia Cells

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 665
Author(s):  
Margot S.F. Roeten ◽  
Johan van Meerloo ◽  
Zinia J. Kwidama ◽  
Giovanna ter Huizen ◽  
Wouter H. Segerink ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cell Lines ◽  
Proteasome Inhibitor ◽  
Ex Vivo ◽  
Lymphoblastic Leukemia ◽  
Unmet Need ◽  
Leukemia Cell ◽  
Leukemia Cells ◽  
Cross Resistance ◽  
Proteasome Subunit

At present, 20–30% of children with acute leukemia still relapse from current chemotherapy protocols, underscoring the unmet need for new treatment options, such as proteasome inhibition. Ixazomib (IXA) is an orally available proteasome inhibitor, with an improved safety profile compared to Bortezomib (BTZ). The mechanism of action (proteasome subunit inhibition, apoptosis induction) and growth inhibitory potential of IXA vs. BTZ were tested in vitro in human (BTZ-resistant) leukemia cell lines. Ex vivo activity of IXA vs. BTZ was analyzed in 15 acute lymphoblastic leukemia (ALL) and 9 acute myeloid leukemia (AML) primary pediatric patient samples. BTZ demonstrated more potent inhibitory effects on constitutive β5 and immunoproteasome β5i proteasome subunit activity; however, IXA more potently inhibited β1i subunit than BTZ (70% vs. 29% at 2.5 nM). In ALL/AML cell lines, IXA conveyed 50% growth inhibition at low nanomolar concentrations, but was ~10-fold less potent than BTZ. BTZ-resistant cells (150–160 fold) displayed similar (100-fold) cross-resistance to IXA. Finally, IXA and BTZ exhibited anti-leukemic effects for primary ex vivo ALL and AML cells; mean LC50 (nM) for IXA: 24 ± 11 and 30 ± 8, respectively, and mean LC50 for BTZ: 4.5 ± 1 and 11 ± 4, respectively. IXA has overlapping mechanisms of action with BTZ and showed anti-leukemic activity in primary leukemic cells, encouraging further pre-clinical in vivo evaluation.

scholarly journals Increase in polymorphonuclear myeloid-derived suppressor cells and regulatory T-cells in children with B-cell acute lymphoblastic leukemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asmaa M. Zahran ◽  
Azza Shibl ◽  
Amal Rayan ◽  
Mohamed Alaa Eldeen Hassan Mohamed ◽  
Amira M. M. Osman ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Critical Role ◽  
Suppressor Cells ◽  
Healthy Controls ◽  
Blast Cells ◽  
Cell Acute Lymphoblastic Leukemia ◽  
The Impact

AbstractOur study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients’ clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children’s Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.

scholarly journals Reduced Flow-Mediated Dilatation Is Not Related to COVID-19 Severity Three Months after Hospitalization for SARS-CoV-2 Infection

2021 ◽  
Vol 10 (6) ◽  
pp. 1318
Author(s):  
Marianne Riou ◽  
Walid Oulehri ◽  
Cedric Momas ◽  
Olivier Rouyer ◽  
Fabienne Lebourg ◽  
...  
Keyword(s):  
Vascular Endothelium ◽  
Matched Control ◽  
Acute Infection ◽  
Critical Role ◽  
Lung Damage ◽  
Vascular Effect ◽  
Flow Mediated Dilatation ◽  
Artery Flow

The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide, with more than two million deaths. Evidence indicates the critical role of the vascular endothelium in its pathophysiology but, like potential changes in functional vasodilation, the vascular effect of SARS-CoV-2 at a given distance from the acute infection is largely unknown. We assessed brachial artery flow-mediated dilatation (FMD) in 27 COVID-19 patients needing conventional or intensive care unit hospitalization, three months after SARS-CoV-2 infection diagnosis and in nine age- and sex- matched control subjects. Interestingly, the FMD was lower in COVID-19 patients as compared to controls (8.2 (7.2–8.9) vs. 10.3 (9.1–11.7)); p = 0.002, and half of the hospitalized COVID-19 survivors presented with a reduced FMD < 8% at three months of COVID-19 onset. Impaired FMD was not associated with severe or critical SARS-CoV-2 infection, reflected by ICU hospitalization, total hospitalization duration, or severity of lung damage. In conclusion, reduced FMD is often observed even three months after hospitalization for SARS-CoV-2 infection, but such alteration predominantly appears to not be related to COVID-19 severity. Longer and larger follow-up studies will help to clarify the potential prognosis value of FMD among COVID-19 patients, as well as to further determine the mechanisms involved.

scholarly journals Human acute leukemia cell line with the t(4;11) chromosomal rearrangement exhibits B lineage and monocytic characteristics

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 21-31 ◽  
Author(s):  
RC Stong ◽  
SJ Korsmeyer ◽  
JL Parkin ◽  
DC Arthur ◽  
JH Kersey
Keyword(s):  
Acute Leukemia ◽  
Cell Line ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Leukemic Cells ◽  
Leukemia Cell Line ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Immunoglobulin Gene ◽  
A Cell ◽  
B Lineage

Abstract A cell line, designated RS4;11, was established from the bone marrow of a patient in relapse with an acute leukemia that was characterized by the t(4;11) chromosomal abnormality. The cell line and the patient's fresh leukemic cells both had the t(4;11)(q21;q23) and an isochromosome for the long arm of No. 7. Morphologically, all cells were lymphoid in appearance. Ultrastructurally and cytochemically, approximately 30% of the cells possessed myeloid features. The cells were strongly positive for terminal deoxynucleotidyl transferase. They were HLA-DR positive and expressed surface antigens characteristic for B lineage cells, including those detected by anti-B4, BA-1, BA-2, and PI153/3. Immunoglobulin gene analysis revealed rearrangements of the heavy chain and kappa chain genes. The cells lacked the common acute lymphoblastic leukemia antigen and antigenic markers characteristic of T lineage cells. The cells reacted with the myeloid antibody 1G10 but not with other myeloid monoclonal antibodies. Treatment with 12-O-tetradecanoyl- phorbol-13-acetate induced a monocyte-like phenotype demonstrated by cytochemical, functional, immunologic, and electron microscopic studies. The expression of markers of both early lymphoid and early myeloid cells represents an unusual phenotype and suggests that RS4;11 represents a cell with dual lineage capabilities. To our knowledge, RS4;11 is the first cell line established from t(4;11)-associated acute leukemia.

scholarly journals Critical Role of c-Myc in Acute Myeloid Leukemia Involving Direct Regulation of miR-26a and Histone Methyltransferase EZH2

2011 ◽  
Vol 2 (5) ◽  
pp. 585-592 ◽  
Author(s):  
B. Salvatori ◽  
I. Iosue ◽  
N. Djodji Damas ◽  
A. Mangiavacchi ◽  
S. Chiaretti ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Critical Role ◽  
Histone Methyltransferase ◽  
Direct Regulation ◽  
Acute Myeloid

Breakpoint junctions of chromosome 9p deletions in two human glioma cell lines

1994 ◽  
Vol 14 (11) ◽  
pp. 7604-7610
Author(s):  
H M Pomykala ◽  
S K Bohlander ◽  
P L Broeker ◽  
O I Olopade ◽  
M O Díaz
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Repetitive Sequences ◽  
Leukemia Cell ◽  
Chromosome 9 ◽  
Breakpoint Junction ◽  
Leukemia Cell Lines ◽  
Long Interspersed Nuclear Elements

Interstitial deletions of the short arm of chromosome 9 are associated with glioma, acute lymphoblastic leukemia, melanoma, mesothelioma, lung cancer, and bladder cancer. The distal breakpoints of the deletions (in relation to the centromere) in 14 glioma and leukemia cell lines have been mapped within the 400 kb IFN gene cluster located at band 9p21. To obtain information about the mechanism of these deletions, we have isolated and analyzed the nucleotide sequences at the breakpoint junctions in two glioma-derived cell lines. The A1235 cell line has a complex rearrangement of chromosome 9, including a deletion and an inversion that results in two breakpoint junctions. Both breakpoints of the distal inversion junction occurred within AT-rich regions. In the A172 cell line, a tandem heptamer repeat was found on either side of the deletion breakpoint junction. The distal breakpoint occurred 5' of IFNA2; the 256 bp sequenced from the proximal side of the breakpoint revealed 95% homology to long interspersed nuclear elements. One- and two-base-pair overlaps were observed at these junctions. The possible role of sequence overlaps, and repetitive sequences, in the rearrangement is discussed.

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