scholarly journals The expression of PTEN and INPP4B and their clinical significance in patients with acute myeloid leukemia

2019 ◽  
Vol 17 ◽  
pp. 205873921985740
Author(s):  
Haobin Song ◽  
Yuanda Zhang ◽  
Yan Liu ◽  
Haiyan Hu ◽  
Qing Zhao ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
Inositol Polyphosphate ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Acute Myelogenous ◽  
Acute Myeloid

This study investigates the expression of phosphatase and tensin homolog (PTEN) and Inositol polyphosphate 4-phosphatase type II (INPP4B) in children with acute myeloid leukemia. The levels of PTEN and INPP4B in bone marrow, from 95 acute myelogenous leukemia (AML) patients and 84 controls, respectively, were assessed by immunohistochemistry, quantitative polymerase chain reaction (qPCR), and Western blot. The prognosis was followed up and investigated and the correlation analysis was made. We found that the expression levels of PTEN and INPP4B were significantly lower in the AML group than those in the control group ( P < 0.05). The survival time was lower in PTEN and INPP4B negative children relative to PTEN and INPP4B positive children ( P < 0.05). In AML patients, INPP4B and PTEN expression was positively correlated (r = 0.552, P = 0.000). In conclusion, the levels of INPP4B and PTEN were reduced significantly and correlated positively in AML patients accompanying with abnormal karyotypes. The current investigation of INPP4B and PTEN could give new insight into targeted therapy for AML.

Results of High Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Acute Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5438-5438
Author(s):  
Kenneth A. Ault ◽  
Delvyn Caedren Case ◽  
Marjorie A. Boyd ◽  
Thomas J. Ervin ◽  
Frederick Aronson ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Myelogenous Leukemia ◽  
Myeloid Leukemia ◽  
Medical Center ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Transplant Program ◽  
Maine Medical ◽  
Acute Myelogenous ◽  
Acute Myeloid

Abstract 43 patients with acute myeloid leukemia have undergone transplantation at our institution over the past 14 years. Patient selection criteria included age less than 70 years, creatinine less than 2mg/ml, no active infection, cardiac ejection fraction >40%, DLCO > 50% of predicted and no other co-morbid conditions that would jeopardize survival. 39 patients were in first remission, 4 were in second or higher remission. 3 patients had favorable cytogenetics, 40 had intermediate or unfavorable cytogenetics. After achieving remission for at least 30 days, patients were consolidated with Etoposide and AraC, followed by G-CSF. Hematopoietic stem cells were collected when the WBC rebounded to at least 10,000/μl. The target dose of CD34 positive cells was 5×106/kg. The minimum dose given was 2.3 × 106/kg). High dose therapy consisted of Busulfan 1mg/kg and Etoposide 60mg/kg. The average age at transplantation was 42 years (range 20 to 61). Days of neutropenia (AGC<500/μl) ranged from 2 to 10 (average 5.2). The median length of follow up is 4.0 years. Kaplan-Meier progression-free survival is 38% at 5 years and 35% at 10 years. Currently 26 patients are alive, and 23 are free from progression. Overall survival is 60%. Maine Medical Center Autologous HPC Transplant Program Acute Myelogenous Leukemia Maine Medical Center Autologous HPC Transplant Program Acute Myelogenous Leukemia

scholarly journals RUNX1 gene expression in Egyptian acute myeloid leukemia patients: may it have therapeutic implications?

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Fadwa Said ◽  
Roxan E. Shafik ◽  
Naglaa M. Hassan
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Gene Expression Level ◽  
Expression Level ◽  
Control Group ◽  
Therapeutic Implications ◽  
Number Of Patients ◽  
Acute Myeloid

Abstract Background Acute myeloid leukemia represents the highest percentage of all adult acute leukemia variants. Runt-related transcription factor1 (RUNX1), a transcription factor with a known tumor suppressor function, was recently reported as a tumor promoter in acute myeloid leukemia (AML). We investigated the role of RUNX1 gene expression level in Egyptian AML patients and delineated its clinical significance. Results We measured RUNX1 gene expression level using reverse transcription-quantitative polymerase chain reaction and found that the RUNX1 gene expression level was significantly higher than the control group (p < 0.001). Patients with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations had a higher expression level of RUNX1 (p = 0.023). The male patients expressed a significantly higher level of RUNX1 (p = 0.046). Conclusions The RUNX1 gene is highly expressed in Egyptian AML patients. It has a relation to FLT3-ITD, which may give a clue that patients carrying this mutation may benefit from new treatments that target RUNX1 in the future. Further studies on a larger number of patients with different ethnic groups may give a clearer vision of the therapeutic implications of a new molecular target.

scholarly journals Decitabine Act As Demethylation Modulators in Acute Myeloid Leukemia for Reversal of Drug Resistance

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5218-5218
Author(s):  
Zhixiang Wang ◽  
Xuejie Jiang ◽  
Kaikai Huang ◽  
Changxin Yin ◽  
Qingxiu Zhong ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Myelogenous Leukemia ◽  
Cell Protein ◽  
Control Group ◽  
Acute Myelocytic Leukemia ◽  
Inhibition Effect ◽  
A Cells ◽  
Acute Myeloid

Abstract Background and objectives The DNA methyltransferase inhibitors decitabine represent archetypal drugs for epigenetic cancer therapy. One alternative approach for the treatment of (Acute Myelocytic Leukemia) AML is the use of hypomethylating agents, including the 5-aza-2-deoxycytidine (decitabine; DAC) and other epigenetic regulators. However, the exact mechanism of DAC for drug resistance AML remains poorly understood. We conducted this study to explore how DAC regulated the sensitivity to adriamycin and aclacinomycin of AML cell line HL60/ADR and assessed the efficacy and safety of decitabine-based induction treatment patients with refractory acute myeloid leukemia. Methods In this study, we analyzing cell proliferation of HL60, HL60/ADR and KG1-¦Á cells treated by DAC against control group detected with MTS assay. Then the changes of genes methylation were determined using Methylation specific PCR (MSP), stained with anti-CD11b, before being analyzed for cell markers with flow cytometric analysis. The cell protein levels were checked with Western blotting as described elsewhere. Data were collected from refractory acute myelogenous leukemia (AML) patients treated with homoharringtonine, cytarabine, and aclarubicin after decitabine (D-HAA). Control group consisted of fludarabine, cytarabine with or without Granulocyte Colony-Stimulating Factor between 2012 and 2014. Results Different dose of DAC had proliferative inhibition effect on HL-60 cells, with time-dose dependent relationship. But the proliferative inhibition of DAC in KG1-¦Á and HL-60/ADR cells was not so effective. After been treated with 1¦ÌM DAC for 72 hours, HL-60/ADR cells were cultured with 0.5µg/ml adriamycin 1 hour. Adriamycin positive cells in DAC group were higher than control group, and the proliferative inhibition effect of adriamycin (P<0.001) and aclacinomycin (P<0.001) on HL60/ADR cells was increased (Figure 1). 1¦ÌM DAC significantly induced expression of CD11b on HL-60/ADR and KG1-¦Á cells, accompanied by cellular changes of differentiation (decreased nuclear¨Ccytoplasmic ratio, nuclear condensation, segmentation or lobulation, cytoplasmic granulation or vacuolization). Followed the increased the sensitivity of adriamycin, DNMT1 and SPRPs gene methylation was down-regulated. And ¦Â-catenin protein in nuclear was depressed after treatment of DAC. We enrolled 75 patients, of whom 71 were included in the intention-to-treat analysis. 65.2% patients in the D-HAA group achieved complete remission versus 29.2% in the FA/FLAG group (P=0.031). 2-year disease-free survival and overall survival were better in D-HAA group than FA/FLAG group (P=0.020, P=0.025; Figure 2). Conclusion These findings provide evidence for clinic protocols using DAC to reversed drug resistance in refractory AML cell. Disclosures No relevant conflicts of interest to declare.

scholarly journals Runx1 Gene in Acute Myeloid Leukemia: Expression Level Significance and Impact on Clinical Features

2020 ◽  
Author(s):  
Fadwa Said Abdelazim Mohamed ◽  
Roxan E Shafik ◽  
Naglaa M. Hassan
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Gene Expression Level ◽  
Expression Level ◽  
Control Group ◽  
Runx1 Gene ◽  
Number Of Patients ◽  
Acute Myeloid

Abstract Background Acute myeloid leukemia represents the highest percentage of all adult acute leukemia variants. Runt-related transcription factor1 (RUNX1), a transcription factor with a known tumor suppressor function was recently reported as a tumor promotor in AML. We investigated the role of RUNX1 geneexpression levelin Egyptian AML patients and delineateits clinical significance. Methods This study recruited 91 AML patients that were recently diagnosed at our hospital with 14 healthy age- and sex-matched donors of bone marrow transplantation unit. We measured RUNX1 gene expression level using reverse transcription–quantitative polymerase chain reaction. Results We found that RUNX1 gene expression level was significantly higher compared to the control group (p < 0.001). Patients with FLT3 mutations had the higher expression level of RUNX1 (p=0.023). The male patients expressed significantly higher level of RUNX1 (p=0.046). Conclusion The RUNX1 gene expression may serve as a diagnostic marker in Egyptian AML patients. Its relation to FLT3 may give clue that patients carrying this mutation may benefit fromnew treatments that target RUNX1 in the future. Further studies on a larger number of patients and different ethnic groupsmay give a clearer vision about this new molecular therapeutic target.

scholarly journals Analyzing How Elderly Acute Myeloid Leukemia Patients Are Treated, an Institutional Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5849-5849
Author(s):  
Christopher Allen Willner ◽  
Mohammad Muhsin Chisti ◽  
Michaela Soriano ◽  
James Huang
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Data Analysis ◽  
Induction Therapy ◽  
Acute Myelogenous Leukemia ◽  
Myeloid Leukemia ◽  
Myelogenous Leukemia ◽  
Elderly Populations ◽  
Acute Myelogenous ◽  
Acute Myeloid

Rationale: Treatment of acute myelogenous leukemia (AML) remains a challenge in elderly populations, those with comorbid conditions, and patients with poor performance status indices. The optimal choice for induction therapy as well as further agent selection is unclear, and current guidelines recommend enrollment in a controlled clinical trial. Methods: Institutional cases of AML via an electronic medical record query performed in November 2017 containing cases of AML in patients 65 years of age or greater from 01/01/2000 to 06/21/2017 were extracted. Instances of acute myelogenous leukemia were identified by ICD codes. Age, gender, induction therapy, cytogenetics, molecular analyses, and overall survival were collected. Results: A total of 61 cases of AML in patients aged 65 or greater were identified, with those having incomplete data being excluded from analysis. The mean age of included patients was 78.9 years of age, 35 were male and 26 were female. 60 confirmed deaths were recorded. 26 patients received conventional 7+3 (42.6%), 22 received a hypomethylating agent (HMA) (31.1%), 16 (26.2%) did not receive treatment. Conclusion: Our institutional data showed overall survival was significantly longer when treated with 7+3, 354 days (95% CI [93, 614]), vs. 61 days (95% CI [15, 107]). Similarly, OS was significantly longer when treated with HMA, 303 days (95% CI [23, 583]). Risk of death, accordingly, was as follows: 7+3 HR .347 (.179-.672), HMA HR .348 (.173-.703). Our institutional mortality data reasonably reflected SEER data analysis reported by Medeiros et al concerning untreated patients, but trended toward a greater OS for those treated with 7+3 or HMA. Registry data, as well as our institutional data, demonstrate a survival benefit to intensive chemotherapy and palliative chemotherapy, while controlled trials have not shown this benefit consistently in elderly populations. Practices regarding induction therapy vary greatly between institutions. Determination of which elderly patients to treat with intensive therapy remains difficult. References: Almeida AM, Ramos F. Acute myeloid leukemia in the older adults. Leuk Res Rep. 2016;6:1-7. Eleni LD, Nicholas ZC, Alexandros S. Challenges in treating older patients with acute myeloid leukemia. J Oncol. 2010;2010:943823. Medeiros BC, Satram-hoang S, Hurst D, Hoang KQ, Momin F, Reyes C. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94(7):1127-38. Disclosures Chisti: Eli Lilly: Speakers Bureau; Medscape: Honoraria; UpToDate: Honoraria.

scholarly journals DNA damage in acute myeloid leukemia patients of Northern Mexico

2017 ◽  
Author(s):  
Martha I. Dávila-Rodríguez ◽  
Elva I. Cortés-Gutiérrez ◽  
Roberto Hernández-Valdés ◽  
Karla Guzmán-Cortés ◽  
Rosa E. De León-Cantú ◽  
...  
Keyword(s):  
Dna Damage ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fluorescent In Situ Hybridization ◽  
Control Group ◽  
Repair Pathway ◽  
Blood Leukocytes ◽  
Northern Mexico ◽  
Acute Myeloid

The purpose of this study was to evaluate DNA damage in the whole genome of peripheral blood leukocytes from patients with acute myeloid leukemia (AML) compared with a control group using DNA breakage detection-fluorescent in situ hybridization (DBD-FISH). Our results suggest that the DNA damage detected in patients with newly diagnosed AML was similar to that observed for the controls; this might be explained by the stimulation of a repair pathway by the pathogenesis itself. These findings indicate that inhibiting the repair pathway could be proposed to enhance the efficacy of chemotherapy.

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