Analysis of the relationship between Scl transcription factor complex protein expression patterns and the effects of LiCl on ATRA-induced differentiation in blast cells from patients with acute myeloid leukemia

2004 ◽  
Vol 28 (11) ◽  
pp. 1227-1237 ◽  
Author(s):  
Anna M. Rice ◽  
Kathleen M. Holtz ◽  
Judith Karp ◽  
Sandra Rollins ◽  
Alan C. Sartorelli
Keyword(s):  
Acute Myeloid Leukemia ◽  
Transcription Factor ◽  
Protein Expression ◽  
Myeloid Leukemia ◽  
Expression Patterns ◽  
Complex Protein ◽  
Blast Cells ◽  
The Relationship ◽  
Transcription Factor Complex ◽  
Acute Myeloid

scholarly journals Clinical relevance of proteomic profiling in de novo pediatric acute myeloid leukemia: a Children’s Oncology Group study

Haematologica ◽  
2022 ◽  
Author(s):  
Fieke W. Hoff ◽  
Anneke D. Van Dijk ◽  
Yihua Qiu ◽  
Chenyue W. Hu ◽  
Rhonda E. Ries ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Protein Expression ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Expression Patterns ◽  
Chemotherapeutic Agents ◽  
Classification Systems ◽  
Proteomic Profiling ◽  
Pediatric Acute Myeloid Leukemia ◽  
Acute Myeloid

Pediatric acute myeloid leukemia (AML) remains a fatal disease for at least 30% of patients, stressing the need for improved therapies and better risk stratification. As proteins are the unifying feature of (epi)genetic and environmental alterations, and are often targeted by novel chemotherapeutic agents, we studied the proteomic landscape of pediatric AML. Protein expression and activation levels were measured in 500 bulk leukemic patient samples and 30 control CD34+ samples, using the reverse phase protein arrays with 296 strictly validated antibodies. The multi-step “MetaGalaxy” analysis methodology was applied and identified nine protein expression signatures (PrSIG), based on strong recurrent protein expression patterns. PrSIGs were associated with cytogenetics and mutational state, and with both favorable or unfavorable prognosis. Analysis based on treatment (i.e., ADE vs. ADE plus bortezomib (ADEB)) identified three PrSIGs that did better with ADEB vs. ADE. When PrSIGs were studied in the context of genetic subgroups, PrSIGs were independently prognostic after multivariate analysis, suggesting a potential value for proteomics in combination with current classification systems. Proteins with universally increased (n=7) or decreased (n=17) expression were observed across PrSIGs. Expression of certain proteins significantly differentially expressed from normal could be identified, forming a hypothetical platform for personalized medicine.

scholarly journals The Relationship between Clinical Feature, Complex Immunophenotype, Chromosome Karyotype, and Outcome of Patients with Acute Myeloid Leukemia in China

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Bingjie Ding ◽  
Lanlan Zhou ◽  
Xuejie Jiang ◽  
Xiaodong Li ◽  
Qingxiu Zhong ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Normal Karyotype ◽  
Clinical Feature ◽  
Complex Karyotype ◽  
Blast Cells ◽  
The Relationship ◽  
Mixed Phenotype ◽  
Acute Myeloid

Mixed phenotype acute leukemia (MPAL) is a complex entity expressing both lymphoid and myeloid immunophenotyping. In the present study, 47 MPAL, 60 lymphoid antigen-positive acute myeloid leukemia (Ly+AML), and 90 acute myeloid leukemia with common myeloid immunophenotype (Ly−AML) patients were investigated. We found that, in MPAL patients, there were high proportions of blast cells in bone marrow and incidence of hepatosplenomegaly, lymphadenopathy, and Philadelphia chromosome. The overall survival (OS) and relapse-free survival (RFS) in MPAL patients were significantly shorter than those in Ly+AML and Ly−AML. With regard to the patients with normal karyotype only, the OS and RFS of MPAL were significantly lower than those of the Ly+AML and Ly−AML; but there were no significant differences in OS and RFS among the patients with complex karyotype. The OS rates of 3 groups with complex karyotype were lower than those of patients with normal karyotype. In Cox multivariate analysis, complex karyotype was an independent pejorative factor for both OS and RFS. Therefore, MPAL is confirmed to be a poor-risk disease while Ly+AML does not impact prognosis. Complex karyotype is an unfavorable prognosis factor in AML patients with different immunophenotype. Mixed immunophenotype and complex karyotype increase the adverse risk when they coexist.

scholarly journals RELATIONSHIP OF BLAST CELL IMMUNOPHENOTYPE WITH REMISSION IN ACUTE MYELOID LEUKEMIA IN CHILDREN

2020 ◽  
Vol 19 (4) ◽  
pp. 45-53
Author(s):  
A. D. Palladina ◽  
A. V. Popa ◽  
V. G. Nikitaev ◽  
K. L. Kondratchik ◽  
N. A. Kupryshina ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tumor Cells ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Remission Rate ◽  
Specific Gene ◽  
Blood Leukocytes ◽  
Blast Cells ◽  
The Relationship ◽  
Acute Myeloid

Introduction. Acute myeloid leukemia (AML) is a clonal disease of the blood system that occurs as a result of mutations in the genome of hematopoietic progenitor cells. As a result of mutations, the linear differentiation of hematopoietic cells is replaced by the proliferation of malignant myeloid progenitors. Currently, the risk group for AML in children is determined mainly by the presence of specific gene and chromosomal abnormalities and an increased level of peripheral blood leukocytes. The features of the immunophenotype of blast cells can also influence the course of the disease.The aim of the work is to assess the relationship between the immunophenotypic parameters of blast cells and the probability of achieving remission in children with AML.Materials and methods. The study included 109 patients aged 3 months to 17 years who received treatment according to the AML BFM 87, AML BFM 2004, NII DOG AML 2007 и NII DOG AML 2012 protocol in the period from 1991 to 2020.Results. The study showed the relationship between the probability of achieving remission and the presence of markers CD33, CD19 and CD14 on tumor cells. Expression of lymphoid antigen CD19 on blasts was associated with a higher rate of remission (73.0 % vs 95.5 %, p = 0.027). The absence of the linearly associated myeloid marker CD33 negatively correlated with the remission rate (61.1 % vs 87.7 %, p = 0.007). In the presence of monocyte antigen CD14 on blasts, the probability of achieving remission was low (95 % vs 50 %, p = 0.013).Conclusion. Characteristics of the immunophenotype of tumor cells in AML in children are associated with the probability of achieving remission.

scholarly journals Decitabine shows anti-acute myeloid leukemia potential via regulating the miR-212-5p/CCNT2 axis

2020 ◽  
Vol 15 (1) ◽  
pp. 1013-1023
Author(s):  
Lina Xing ◽  
Jinhai Ren ◽  
Xiaonan Guo ◽  
Shukai Qiao ◽  
Tian Tian
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Myeloid Leukemia ◽  
Luciferase Reporter ◽  
Expression Levels ◽  
Proliferation And Apoptosis ◽  
Polymerase Chain ◽  
The Relationship ◽  
Acute Myeloid

AbstractPrevious research has revealed the involvement of microRNA-212-5p (miR-212-5p) and cyclin T2 (CCNT2) in acute myeloid leukemia (AML). However, whether the miR-212-5p/CCNT2 axis is required for the function of decitabine in AML has not been well elucidated. Quantitative reverse transcription-polymerase chain reaction was used to examine enrichment of miR-212-5p. The relationship between CCNT2 and miR-212-5p was verified by the luciferase reporter assay. Cell apoptosis was evaluated by flow cytometry and western blot. CCK-8 assay was performed to determine cell viability. Decitabine significantly repressed cell viability, while promoted cell apoptosis. Meanwhile, the expression levels of cyclinD1, CDK4, and Bcl-2 were suppressed in cells with decitabine exposure, but Bax and caspase-3 expression levels were upregulated. Besides, miR-212-5p upregulation had the similar function with decitabine in AML cell proliferation and apoptosis. Subsequently, restoration of CCNT2 attenuated miR-212-5p overexpression-induced effects in Kasumi-1 and SKNO-1 cells. In addition, miR-212-5p depletion reversed decitabine-induced CCNT2 downregulation. The miR-212-5p/CCNT2 axis had an implication in the anti-leukemic effect of decitabine in AML.

microRNAs in acute myeloid leukemia: Expression patterns, correlations with genetic and clinical parameters, and prognostic significance

2009 ◽  
pp. n/a-n/a ◽  
Author(s):  
Rotraud Wieser ◽  
Marcel Scheideler ◽  
Hubert Hackl ◽  
Maria Engelmann ◽  
Christine Schneckenleithner ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Expression Patterns ◽  
Prognostic Significance ◽  
Clinical Parameters ◽  
Acute Myeloid

scholarly journals The ETO Protein Disrupted in t(8;21)-Associated Acute Myeloid Leukemia Is a Corepressor for the Promyelocytic Leukemia Zinc Finger Protein

2000 ◽  
Vol 20 (6) ◽  
pp. 2075-2086 ◽  
Author(s):  
Ari M. Melnick ◽  
Jennifer J. Westendorf ◽  
Adam Polinger ◽  
Graeme W. Carlile ◽  
Sally Arai ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Transcription Factor ◽  
Zinc Finger ◽  
Transcriptional Repression ◽  
Histone Deacetylases ◽  
Myeloid Leukemia ◽  
Histone Deacetylase Inhibitors ◽  
Promyelocytic Leukemia ◽  
Promyelocytic Leukemia Zinc Finger ◽  
Acute Myeloid

ABSTRACT The ETO protein was originally identified by its fusion to the AML-1 transcription factor in translocation (8;21) associated with the M2 form of acute myeloid leukemia (AML). The resulting AML-1–ETO fusion is an aberrant transcriptional regulator due to the ability of ETO, which does not bind DNA itself, to recruit the transcriptional corepressors N-CoR, SMRT, and Sin3A and histone deacetylases. The promyelocytic leukemia zinc finger (PLZF) protein is a sequence-specific DNA-binding transcriptional factor fused to retinoic acid receptor α in acute promyelocytic leukemia associated with the (11;17)(q23;q21) translocation. PLZF also mediates transcriptional repression through the actions of corepressors and histone deacetylases. We found that ETO is one of the corepressors recruited by PLZF. The PLZF and ETO proteins associate in vivo and in vitro, and ETO can potentiate transcriptional repression by PLZF. The N-terminal portion of ETO forms complexes with PLZF, while the C-terminal region, which was shown to bind to N-CoR and SMRT, is required for the ability of ETO to augment transcriptional repression by PLZF. The second repression domain (RD2) of PLZF, not the POZ/BTB domain, is necessary to bind to ETO. Corepression by ETO was completely abrogated by histone deacetylase inhibitors. This identifies ETO as a cofactor for a sequence-specific transcription factor and indicates that, like other corepressors, it functions through the action of histone deactylase.

scholarly journals Human-level recognition of blast cells in acute myeloid leukemia with convolutional neural networks

2019 ◽  
Author(s):  
Christian Matek ◽  
Simone Schwarz ◽  
Karsten Spiekermann ◽  
Carsten Marr
Keyword(s):  
Acute Myeloid Leukemia ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
White Blood Cells ◽  
Cell Types ◽  
Hematologic Malignancies ◽  
Malignant Cell ◽  
Morphological Examination ◽  
Blast Cells ◽  
Acute Myeloid

AbstractReliable recognition of malignant white blood cells is a key step in the diagnosis of hematologic malignancies such as Acute Myeloid Leukemia. Microscopic morphological examination of blood cells is usually performed by trained human examiners, making the process tedious, time-consuming and hard to standardise.We compile an annotated image dataset of over 18,000 white blood cells, use it to train a convolutional neural network for leukocyte classification, and evaluate the network’s performance. The network classifies the most important cell types with high accuracy. It also allows us to decide two clinically relevant questions with human-level performance, namely (i) if a given cell has blast character, and (ii) if it belongs to the cell types normally present in non-pathological blood smears.Our approach holds the potential to be used as a classification aid for examining much larger numbers of cells in a smear than can usually be done by a human expert. This will allow clinicians to recognize malignant cell populations with lower prevalence at an earlier stage of the disease.

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