Circulating Endothelial Cells Are an Indicator of Response to Treatment in Acute Myeloid Leukemia Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2776-2776
Author(s):  
Agnieszka Wierzbowska ◽  
Tadeusz Robak ◽  
Anna Krawczynska ◽  
Agata Wrzesien-Kus ◽  
Agnieszka Pluta ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Circulating Endothelial Cells ◽  
Response To Treatment ◽  
Control Group ◽  
Healthy Controls ◽  
Endothelial Progenitor ◽  
Activation Markers ◽  
Acute Myeloid

Abstract Introduction. The circulating endothelial cells (CEC) are proposed to be a noninvasive marker of angiogenesis. The number of CEC in peripheral blood of patients (pts) with acute myeloid leukemia (AML) has not been investigated so far. Patients and Methods. We evaluated the count of resting (rCEC) and activated (aCEC) CEC and circulating endothelial progenitor cells (CEPC) as well as apoptotic CEC (CECAnnV+) in 62 AML pts at the time of diagnosis and 30 healthy controls. Additionally in 26 pts measurements were performed at the time of response evaluation and in 15 pts also 24 h after the first and last dose of chemotherapy. The levels of CEC were correlated with known prognostic factors and response to treatment. CEC were evaluated by the four colour flow cytometry using a panel of previously described monoclonal antibodies and an appropriate analysis gate. CEPC were defined as negative for hematopoietic marker CD45 and positive for endothelial cells markers CD34, CD31 and the endothelial progenitor marker CD133. Resting CEC were defined as CD45−, CD133−, CD31+, CD34+, CD146+ and negative for activation markers (CD105, CD106). CD105 or CD106 positive mature endothelial cells were classified as activated CEC. Apoptotic CEC were CD146 and Annexin V positive. Results. In untreated AML pts we observed 10-fold higher CEC level (median 29,3/μL) than in the control group (2,95/μL) p<0,0001. The numbers of aCEC (12,7/μL), rCEC (12,3/μL) and CEPC (1,7/μL) were significantly higher in AML pts at diagnosis when compared to healthy controls (aCEC 0,9/μL, rCEC 1,6/μL and 0,1/μL; p<0,0001). CECAnnV+ count was also 10-fold higher in AML (1,5/μL) than in controls (0,15/μL; p<0,0001). Both CEC and CECAnnV+ counts did not correlate with WBC, hemoglobin and platelets count as well as percentage of blasts in bone marrow and absolute blast count. The positive correlations between CEC number and CEPC count (r=0,435; p<0,001), CECAnnV+ count (r=0,502; p<0,01) as well as LDH activity (r=0,328; p<0,02) were found. The significant decrease of aCEC and rCEC numbers 24 hours after the first dose of chemotherapy was noted in patients who achieved complete remission (CR)(p<0,04) but not in pts refractory to treatment. Moreover aCEC, rCEC, CEPC and CECAnnV+ counts determined at the time of response’s evaluation were significantly lower then at the time of diagnosis in pts who achieved CR (p<0,01) and did not differ in refractory AML. There was no difference between levels of both viable and apoptotic CEC in AML pts in CR and in the control group (p>0,05). Conclusions. The CEC and CECAnnV+ levels are significantly higher in AML patients than in healthy subjects and correlate with response to treatment. Further investigation should be undertaken to better determine their prognostic and therapeutic value.

The Association of Circulating T Follicular Helper Cells and Regulatory Cells with Acute Myeloid Leukemia Patients

2019 ◽  
Vol 143 (1) ◽  
pp. 19-25
Author(s):  
Zhenxing Guo ◽  
Zhenping Chen ◽  
Yaru Xu ◽  
Yu Zhang ◽  
Liangding Hu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Control Group ◽  
Healthy Controls ◽  
Sample Collection ◽  
Follicular Helper ◽  
Potential Association ◽  
Chemotherapy Patients ◽  
Tgf Β1 ◽  
Acute Myeloid

Objective: This study aims to investigate the association of circulating T follicular helper (cTfh) cells and T follicular regulatory (cTfr) cells with acute myeloid leukemia (AML) patients. Methods: A total of 22 newly diagnosed, untreated AML patients as well as 26 healthy controls were enrolled. Percentages of cTfh and cTfr cells were detected using flow cytometry. Results: Compared to healthy controls, a significantly higher percentage of cTfr cells was observed in AML patients (4.10 ± 11.18 vs. 0.63 ± 0.38%) (p < 0.05). In addition, a significantly lower cTfh/cTfr ratio was found in the AML patients’ group when compared to the control group (9.04 ± 9.19 vs. 11.66 ± 5.68) (p < 0.05). A lower level of plasma IL-2 and TGF-β1 was found in AML patients. Based on the complete remission (CR) response after one cycle of inductive chemotherapy, patients were divided into two groups at sample collection: AML with and without CR. Significantly lower percentages of cTfr cells and a higher cTfh/cTfr ratio were found in the group of AML patients with CR than in the AML patients without CR. Conclusion: There was a significantly higher percentage of cTfr cells in AML patients. cTfr cells may have a potential association with the pathogenesis of AML patients.

Circulating endothelial cells in patients with acute myeloid leukemia

2005 ◽  
Vol 75 (6) ◽  
pp. 492-497 ◽  
Author(s):  
Agnieszka Wierzbowska ◽  
Tadeusz Robak ◽  
Anna Krawczynska ◽  
Agata Wrzesien-Kus ◽  
Agnieszka Pluta ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Circulating Endothelial Cells ◽  
Acute Myeloid

The Polymorphisms Of Base Excision Repair Genes Influence The Cytogenetic Risk Factors In Acute Myeloid Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1355-1355
Author(s):  
Atsushi Iwasaki ◽  
Takayuki Saitoh ◽  
Yasuhiro Nitta ◽  
Batchimeg Norjimaa ◽  
Chiharu Omiya ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Base Excision Repair ◽  
Myeloid Leukemia ◽  
Excision Repair ◽  
Control Group ◽  
Healthy Controls ◽  
Base Excision ◽  
And Control ◽  
Repair Genes ◽  
Acute Myeloid

Abstract Background Base excision repair (BER) systems have important role for repairing oxidative DNA damage, and known to influence the carcinogenesis and the response to anti-cancer treatments. Although few studies have shown that several DNA repair genes are associated with an increased risk of leukemia, the clinical significance of BER polymorphisms in acute myeloid leukemia (AML) patients remains unclassified. The aim of this study was to evaluate the impact of polymorphisms in genes encoding four main proteins of BER system: OGG1 Ser326Cys, MUTYH Gln324His, APE1 Asp148Glu, and XRCC1 Arg399Gln, and on the risk of AML. Methods Between December 1991 and May 2013, 99 patients (male/female 55/44, median age 58 years, range 15-86 years) diagnosed as AML and 192 healthy controls were included in this study. Cytogenetic subgroups were classified as good, intermediate, and adverse risk according to NCCN guidelines. Genomic DNA was isolated from peripheral blood using the DNA extraction kit. Genotyping was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Genotype and allele frequencies were compared between patients group and control group by using χ2-test. Probability values <0.05 were considered statistically significant. All patients and healthy controls received written information about the study. This study was approved by the Institutional Research Board of Gunma University Hospital. Results The APE1 Asp/Asp genotype increases the risk of AML (OR 2.30, 95% CI 1.41-3.77, p<0.001), whereas APE1 Glu/Glu genotype reduces the risk of AML (OR 0.34, 95% CI 0.14-0.80, p<0.05). In contrast, there were no significant differences in the genotype frequencies OGG1 Ser326Cys, MUTYH Gln324His, and XRCC1 Arg399Gln between AML patients and control group. Next we compared the frequency of cytogenetic abnormalities according to BER polymorphism. The AML patients with OGG1 Ser/Ser genotype increased the frequencies of (15;17) type (p<0.05) and good risk group. Moreover, the AML patients with MUTYH His/His genotype increased the frequencies of complex type (p<0.02) and reduced the frequencies of t(8;21) type. Conclusions According to our data, BER gene polymorphisms may affect the carcinogenesis and the cytogenetic risk of AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Circulating endothelial cells and their progenitors in acute myeloid leukemia

2016 ◽  
Vol 12 (3) ◽  
pp. 1965-1970 ◽  
Author(s):  
Asmaa Mohammed Zahran ◽  
Sanaa Shaker Aly ◽  
Hanan Ahmed Altayeb ◽  
Arwa Mohammed Ali
Keyword(s):  
Endothelial Cells ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Circulating Endothelial Cells ◽  
Acute Myeloid

scholarly journals Association Analysis of TP53 rs1042522, MDM2 rs2279744, rs3730485, MDM4 rs4245739 Variants and Acute Myeloid Leukemia Susceptibility, Risk Stratification Scores, and Clinical Features: An Exploratory Study

2020 ◽  
Vol 9 (6) ◽  
pp. 1672 ◽  
Author(s):  
Florin Tripon ◽  
Mihaela Iancu ◽  
Adrian Trifa ◽  
George Andrei Crauciuc ◽  
Alina Boglis ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Features ◽  
Exploratory Study ◽  
Multifactor Dimensionality Reduction ◽  
Myeloid Leukemia ◽  
Somatic Mutations ◽  
Response To Treatment ◽  
Healthy Controls ◽  
Tp53 Arg72pro ◽  
Acute Myeloid

This study aimed to explore the associations between the TP53 rs1042522 (TP53 Arg72Pro), MDM2 rs2279744 (MDM2 309T>G), rs3730485 (MDM2 del1518), MDM4 rs4245739 (MDM4 34091 C>A) variants and odds of developing acute myeloid leukemia (AML) in a cohort of 809 adult subjects, consisting of 406 healthy controls and 403 AML patients. Model-based multifactor dimensionality reduction (MB-MDR) framework was used to identify the interactions of the mentioned variants and their association with AML risk. Associations of the mentioned variants with clinical features of AML, somatic mutations, and response to treatment were also evaluated. Significant associations between TP53 rs1042522 and MDM4 rs4245739 variants and AML susceptibility were noticed. MB-MDR and logistic regression analysis revealed an interaction between MDM2 rs2279744 and TP53 rs1042522, between MDM4 rs4245739 and MDM2 rs3730485, as well as significant associations with AML susceptibility. Several associations between the mentioned variants and clinical features of AML and somatic mutations were also noticed. Individually, the variant genotypes of TP53 rs1042522 and MDM4 rs4245739 were associated with AML susceptibility, but their interaction with MDM2 rs2279744 and rs3730485 modulated the risk for AML. The variant genotypes of TP53 rs1042522 were associated with adverse molecular and cytogenetic risk and also with NPM1 mutations.

High Serum Level of Placental Growth Factor (PlGF) Predicts Adverse Overall Survival in Patients with Acute Myeloid Leukemia Treated with Standard Chemotherapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3972-3972
Author(s):  
Agnieszka Wierzbowska ◽  
Anna Krawczynska ◽  
Ewa Wawrzyniak ◽  
Agnieszka Pluta ◽  
Anna Wolska ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Endothelial Cells ◽  
Acute Myeloid Leukemia ◽  
Growth Factor ◽  
Myeloid Leukemia ◽  
Univariate Analysis ◽  
Placental Growth Factor ◽  
Healthy Controls ◽  
Acute Myeloid

Abstract Background: Angiogenesis plays an important role in the pathogenesis of acute myeloid leukemia (AML) and vascular endothelial growth factor (VEGF) is an essential positive regulator of this process. Placental growth factor (PlGF) is a member of VEGF family that exerts its angiogenic action by synergizing with VEGF. There is also evidence that PlGF may be survival factor for angiogenic endothelial cells. The role of PlGF in patients with acute leukemia have not been investigated at all. Material and methods: We measured the plasma concentrations of VEGF and PlGF in 61 patients with newly diagnosed AML and 22 healthy controls using the ELISA assay. Additionally, in AML patients we correlated the plasma levels of angiogenic cytokines with the number of viable (CEC) and apoptotic (CECAnnV+) circulating endothelial cells, known prognostic factors, response to induction therapy as well as overall survival (OS). The AML group consisted of 34 women and 27 men with a median age of 49 years (range 25–76 years). All patient received standard induction chemotherapy (according to 3+7 protocol). Statistical analysis included the following variables: VEGF and PlGF levels, age, sex, performance status, cytogenetic risk group according SWOG, presence of multilineage dysplasia, WBC and PLT count, hemoglobin level, LDH activity, % of bone marrow blasts and CEC as well as CECAnnV+ number. Results: The PlGF and VEGF median levels (23,6 pg/ml and 45,1 pg/ml respectively) were significantly higher in the AML at diagnosis than in the healthy subjects (9,5 pg/ml; p&lt;0,0001 and 25,2 pg/ml; p&lt;0,03 respectively). Moreover, the VEGF level at diagnosis in patients who did not respond to induction chemotherapy was significantly higher than in patients who achieved complete remission (CR) (84,7 vs 31,2 pg/ml; p&lt;0,01). The significant negative correlation between the VEGF and percentage of apopototic CECAnnV+ was also observed. Median follow-up was 12,1 months (range: 1– 43 months). 50 patients (82%) achieved CR. The CR rate in low and high VEGF expressors was respectively 86% and 70% (p=0.07). The CR rate in high- and low PlGF expressors did not differ significantly (74% and 80% respectively). In univariate analysis poor cytogenetics was the only factor associated with increased risk of treatment failure. The median time of OS in analysed group was 15 months. In the univariate analysis high (over median) PlGF levels was associated with shorter OS (p=0.005) (Figure1). Shorter OS was also associated with age&gt;40 years (p=0.009), failure to achieve CR (p=0.009) and higher (&gt;50%) bone marrow infiltration with leukemic blasts (p=0.005). In the multivariate Cox proportional hazard model the elevated PlGF plasma level was strongly associated with shorter OS (p&lt;0.007). The other factors found to influence shorter OS were: high bone marrow infiltration with leukemic blasts (p=0.02), age&gt;40 years (p=0.04), failure to achieve CR (p=0.04). Conclusions: In conclusion we can state that the high plasma concentration of PlGF is associated with poor prognosis in AML patients. Observed in our study significantly higher PlGF level in AML patients compared to healthy controls may indicate that this angiogenic cytokine plays an important, independent of VEGF role in pathogenesis of AML Figure Figure

scholarly journals The prospective prognostic value of the immune checkpoint BTLA expression in adult acute myeloid leukemia patients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sara M. Radwan ◽  
Nooran S. Elleboudy ◽  
Nermeen A. Nabih ◽  
Amal El-kholy ◽  
Amany M. Kamal
Keyword(s):  
Acute Myeloid Leukemia ◽  
Immune Checkpoint ◽  
Myeloid Leukemia ◽  
Immune Surveillance ◽  
Response To Treatment ◽  
Healthy Controls ◽  
Survival Times ◽  
Over Expression ◽  
Kaplan Meier ◽  
Acute Myeloid

Abstract Background One of the crucial functions of the immune system is to prevent tumorigenesis, yet cancer occurs when malignant cells manage to evade immune surveillance via multiple strategies. Accordingly, this study aimed at assessing the potential significance of the novel immune checkpoint B and T lymphocyte attenuator (BTLA) as a prognostic marker in acute myeloid leukemia (AML), in addition to how it relates to response to treatment and patients’ survival. Thus, mRNA expression of BTLA was investigated on peripheral blood in 60 AML patients and 15 healthy controls. Results BTLA expression was found to be significantly elevated (p = 0.024) in the tested AML cases in comparison with healthy controls. Moreover, BTLA was over-expressed in the CD13, CD33, and HLA-DR positive cases as compared to their negative counterparts (p = 0.003; p < 0.001, and p = 0.001, respectively), and cases showing BTLA over-expression had significantly poorer overall survival times (p = 0.001) as confirmed by Kaplan–Meier survival analysis. Conclusion These observations suggest that BTLA over-expression may be associated with reduced immunity against tumors and could be recommended as a promising biomarker for unfavorable prognosis in AML.

Osteopontin - A New Angiogenic Factor Which Correlates with Circulating Endothelial Cells in Acute Myeloid Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1004-1004
Author(s):  
Agnieszka Wierzbowska ◽  
Magdalena Czemerska ◽  
Anna Krawczyńska ◽  
Agnieszka Pluta ◽  
Anna Szmigielska ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Significant Positive Correlation ◽  
Circulating Endothelial Cells ◽  
Response To Treatment ◽  
Positive Correlation ◽  
Ldh Activity ◽  
Acute Myeloid

Abstract Abstract 1004 Poster Board I-26 Objectives: There is evidence that acute myeloid leukemia (AML) development and progression could be determined by the expression profiling of specific angiogenic proteins. Previously we have found that the number of circulating endothelial cells (CEC) and endothelial progenitors (CEP) in peripheral blood of AML patients is a good noninvasive marker of angiogenesis and correlates with tumor mass and response to treatment. Osteopontin (OPN) is hematopoietic stem cell niche component which controls tumor growth and angiogenesis. It promotes VEGF dependent tumor progression, induces endothelial cell survival and migration and modulates expression of angiopoietins. The role of OPN in AML is unknown. We evaluated the level of circulating OPN, angiopoietin-1 (ANG-1) and ANG-2 in AML patients. In addition we correlated the levels of angiogenic cytokines with CEC number, known prognostic factors and response to treatment. Methods: OPN, ANG-1 and ANG-2 were measured in plasma samples in 69 newly diagnosed AML patients with median age 53 (range 18-78 years) and 16 controls with median age 36 (range 22-73 years) using enzyme-linked immunosorbent assay (ELISA). According to median level of cytokines patients were subdivided into “low-expressers” and “high”-expressers group. CEC were evaluated by the four colour flow cytometry using a panel of previously described monoclonal antibodies. CEC deriving from angiogenic microvessels were characterized by CD36 expression. Results: The median levels of circulating OPN (162,5 pg/ml) and ANG-2 (5184 pg/ml) were significantly higher in AML patients as compared to healthy controls (70 pg/ml; p<0.0001 and 2624,3 pg/ml; p<0.001 respectively). In contrast, the level of ANG-1 in AML pts (1038 pg/ml) was lower than in control group (1710 pg/ml; p<0.002). OPN plasma level was significantly higher in AML patients with more than 50% of blasts in the bone marrow (197 pg/ml) and elevated LDH activity (170 pg/ml) compared to group with BM blasts <50% (152 pg/ml; p<0.05) and normal LDH (137,5 pg/ml; p<0.03). In analogy, we found the significant positive correlation between ANG-2, but not ANG-1, with WBC count (p=0.05), circulating blast count (CBC) (p<0.005) and LDH activity (p=0.05). There was no statistical association between the levels of OPN, ANG-1, and ANG-2, and patients' age, sex, AML subtype according FAB classification and cytogenetic risk group. Interestingly, in AML patients OPN level correlated positively with the number of CEC deriving from angiogenic microvessels (p<0.02). Moreover, we observed tendency to positive correlation between ANG-2 level and CD36+ CEC count (p=0.09). In addition, in AML we have found significant positive correlation between OPN and ANG-2 level (p<0.03). From the 49 patients receiving intensive induction chemotherapy, 28 (56%) achieved complete remission (CR). We observed that the CR rate in “low-expressers” of OPN (67%) was higher than in the “high-expressers” (33%), however a difference did not reached statistical significance. This may be due to not very large number of evaluated patients. Conclusions: The levels of circulating OPN and ANG-2, but not ANG-1, are significantly higher in AML patients than in healthy subjects and correlate with tumor burden as well as the number of “angiogenic” circulating endothelial cells. This data clearly demonstrate an important role of circulating OPN as well as ANG-2 in angiogenesis and AML biology. A better understanding of precise functions of OPN and angiopoietins may create new options for therapeutic interventions in AML. Disclosures: Robak: Celgene: Consultancy; Roche: Honoraria, Research Funding; Genmab: Research Funding; Cambridge Antibody Technology: Research Funding; GlaxoSmithKline: Honoraria.

scholarly journals Dysregulation of CCAAT/enhancer binding protein-alpha (CEBPA) expression in the bone marrow of acute myeloid leukemia patients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Naglaa M. Hassan ◽  
Fadwa Said ◽  
Roxan E. Shafik ◽  
Mona S. Abdellateif
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Binding Protein ◽  
Response To Treatment ◽  
Pathological Features ◽  
Poor Prognostic Factor ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Acute Myeloid

Abstract Background Acute myeloid leukemia (AML) is a heterogeneous malignant disease characterized by accumulation of different types of mutations commonly the CCAAT/enhancer binding protein-alpha (CEBPA). However, the dysregulations of CEBPA expression in AML is still a debatable issue. The aim of the current study was to assess CEBPA gene expression in bone marrow (BM) aspiration specimens of 91 AML patients, compared to 20 control donors of bone marrow transplantation (BMT), using RT-PCR. Data were correlated with patients’ clinico-pathological features, response to treatment, progression-free survival (PFS), and overall survival (OS) rates. Results There was overexpression of CEBPA gene in AML patients compared to normal control [1.7 (0.04–25.6) versus 0.17 (0–4.78), respectively, P < 0.001]. Upregulation of CEBPA expression associated significantly with increased BM hypercellularity, total leucocyte counts, peripheral blood blast cell count, and poor PFS (P < 0.001, 0.002, 0.001, and 0.013, respectively). There was no significant association between CEBPA expression and any other relevant clinico-pathological features or OS rates (P = 0.610) of the patients. ROC analysis for biological relevance of CEBPA expression with AML showed that sensitivity and specificity of CEBPA expression at a cut-off value of 0.28 are 92.3% and 78.6%, respectively (P < 0.001). All patients who had CEBPA overexpression and mutant FLT3 showed BM hypercellularity, adverse cytogenetic risk, increased TLC, and PB blast cells count (P = 0.007, P < 0.001, 0.016, and 0.002, respectively). Conclusion CEBPA overexpression could be used as a genetic biological marker for AML diagnosis, as well as a poor prognostic factor for disease progression. It has no impact on OS rates of the patients.

Sign in / Sign up

Export Citation Format

Share Document