scholarly journals The role of neuronal apoptosis inhibitory protein (NAIP) in acute myeloid leukemia patients

2019 ◽  
Vol 50 (2) ◽  
pp. 74-80
Author(s):  
Agnieszka Pluta ◽  
Tadeusz Robak ◽  
Kamil Brzozowski ◽  
Barbara Cebula-Obrzut ◽  
Agata Majchrzak ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Neuronal Apoptosis ◽  
De Novo ◽  
Univariate Analysis ◽  
Malignant Neoplasm ◽  
Inhibitory Protein ◽  
Response To Chemotherapy ◽  
Neuronal Apoptosis Inhibitory Protein ◽  
Acute Myeloid

AbstractAcute myeloid leukemia (AML) is a heterogeneous, highly malignant neoplasm. Apoptosis is a complex process executed by caspases and suppressed by the inhibitor of apoptosis (IAP) family. Neuronal apoptosis inhibitory protein (NAIP), IAP’s member, may play an exceptional role in the mechanisms of tumors’ resistance to chemotherapy. The aims of the study were to assess the expression of NAIP in leukemic blasts of AML patients using flow cytometry and to evaluate its influence on disease outcome. NAIP expression was found in 106 out of 108 patients. A higher complete response rate was associated with a low expression of NAIP, age < 60 yo, and white blood cell count < 20 G/L (p = 0.009, p = 0.033, and p = 0.076, respectively) in univariate analyses and a low NAIP expression and age < 60 yo (p = 0.025 and p = 0.013, respectively) in multivariate analyses. Longer overall survival (OS) in the univariate analysis was influenced by a low NAIP expression, age < 60 yo, and intensive chemotherapy (p = 0.033, p < 0.001, and p < 0.001, respectively). In the intensively treated group, better OS was observed in patients with age < 60 yo, de novo AML, and a low NAIP expression (p = 0.03, p = 0.024, and p = 0.07, respectively). In multivariate analysis, longer OS was associated with age < 60 yo (p = 0.009) and de novo AML (p = 0.007). In conclusion, we suggest that NAIP might play an adverse role in response to chemotherapy.

scholarly journals Pretreatment platelet count predicts survival outcome of patients with de novo non-M3 acute myeloid leukemia

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e4139 ◽  
Author(s):  
Qianying Zhang ◽  
Kanchun Dai ◽  
Laixi Bi ◽  
Songfu Jiang ◽  
Yixiang Han ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Platelet Count ◽  
Predictive Value ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Univariate Analysis ◽  
Survival Outcome ◽  
Cox Regression Analysis ◽  
High Platelet Count ◽  
Acute Myeloid

Background Pretreatment platelet count has been reported as a potential tool to predict survival outcome in several solid tumors. However, the predictive value of pretreatment platelet count remains obscure in de novo acute myeloid leukemia (AML) excluding acute promyelocytic leukemia (M3). Methods We conducted a retrospective review of 209 patients with de novo non-M3 AML in our institute over a period of 8 years (2007–2015). Receiver operating characteristic (ROC) curve analysis was used to determine the optimal platelet (PLT) cutoff in patients. We analyzed the overall survival (OS) and disease free survival (DFS) using the log-rank test and Cox regression analysis. Results By defining the platelet count 50 × 109/L and 120 × 109/L as two cut-off points, we categorized the patients into three groups: low (<50 × 109/L), medium (50–120 × 109/L) and high (>120 × 109/L). On univariate analysis, patients with medium platelet count had longer OS and DFS than those with low or high platelet count. However, the multivariate analysis showed that only longer DFS was observed in patients with medium platelet count than those with low or high platelet count. Conclusion Our findings indicate that pretreatment platelet count has a predictive value for the prognosis of patients with non-M3 AML.

EZH2 Mutations Are Associated with Low Blast Percentage in Bone Marrow and −7/Del(7q) Karyotype in De Novo Acute Myeloid Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2544-2544
Author(s):  
Xiuli Wang ◽  
Haiping Dai ◽  
Qian WANG ◽  
Qinrong Wang ◽  
Yang Xu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Myelogenous Leukemia ◽  
Prognostic Impact ◽  
Coding Region ◽  
Acute Myeloid

Abstract Abstract 2544 Somatic mutation of the EZH2 gene is seen in myelodisplastic syndrome, myelofibrosis, and chronic myelomonocytic leukemia patients. The prevalence and prognostic impact of somatic mutations of EZH2 in patients with acute myelogenous leukemia (AML) remains unknown. In this study, we sought to determine the incidence and clinical implications of somatic EZH2 mutations in 714 patients with de novo AML by PCR amplification of the entire coding region followed by direct bidirectional DNA sequencing. EZH2 mutations were identified in 13/714 (1.8%) of AML patients and occurred almost exclusively in males (11/13, P=0.033). In univariate analysis, the presence of EZH2 mutations was significantly associated with lower blast percentage (21–30%) in bone marrow (P=0.0001) and −7/del(7q) (P=0.025). There was no difference in the incidence of mutations in 13 genes, including ASXL1, CBL, c-KIT, DNMT3A, FLT3, IDH1, IDH2, MLL, NPM1, NRAS, RUNX1, TET2, and WT1, between patients with and without EZH2 mutations. Complete remission, event-free survival or overall survival was similar between AML patients with and without EZH2 mutation (p>0.05). These results demonstrated EZH2 mutation as a recurrent genetic abnormality associated with lower blast percentage in BM and −7/del(7q) in de novo acute myeloid leukemia. Disclosures: No relevant conflicts of interest to declare.

Bmi-1 Expression Is Useful To Design Therapy and To Predict Prognosis in Patients with Acute Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3296-3296
Author(s):  
Moniruddin Chowdhury ◽  
Keichiro Mihara ◽  
Nanae Nakaju ◽  
Sachiko Fukumoto-Hidani ◽  
Yoshihiro Takihara ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Standard Dose ◽  
Intensive Therapy ◽  
Univariate Analysis ◽  
Granulocytic Sarcoma ◽  
High Dose ◽  
Binary Logistic Regression Model ◽  
Acute Myeloid

Abstract Since prognosis of patients with acute myeloid leukemia (AML) is highly variable even in a single subpopulation in FAB classification, it would be useful to find prognostic molecular markers for AML. Thus, we investigated Bmi-1 expression in AML cells by flow cytometry and analyzed whether it predicts prognosis in AML patients and further it is helpful to choose therapies in the modalities of treatment options, because it is known to be required for self-renewal mechanism of leukemic stem cells. Bmi-1 expression in bone marrow or peripheral blood cells was analyzed in 49 patients with AML (M0(n=5), M1(n=7), M2(n=6), M3(n=5), M4(n=8), M5(n=5), M6(n=1)), granulocytic sarcoma(n=1), MDS-AML (n=9), and secondary AML(n=2). Freshly isolated AML cells were stained with a PE-conjugated anti-CD34-antibody followed by fixation and then with anti-Bmi-1-antibody-FITC. All of patients with low Bmi-1 positivity (&lt;35%, n=11) except for de novo AML(M0) entered in complete remission (CR) with single induction chemotherapy(n=5) and accordingly had better overall survival, even though lower dose of chemotherapy (60% of standard dose) was given (n=3). Alternatively, patients with higher percentage of Bmi-1 expression in AML cells (&gt; 70%, n=19) except for AML(M3) progressed to death within two years, unless they were treated with highly intensive therapy such as high dose AraC or allogeneic stem cell transplantation (n=3). Patients with intermediate degree of Bmi-1 expression (35–60%, n=5) responded to standard intensity of chemotherapy (n=2) and are alive for more than two years. Interestingly, patients with MDS-AML (n=9) had high Bmi-1 expression (79%) and all of them have died within 20 months. Binary logistic regression model showed that significant correlation was found among survival status as dependent variable, Bmi-1, and treatment intensity as independent variable (p = 0.004). On the other hand, Univariate analysis did not reveal any relation of Bmi-1 expression to karyotype, age, WBC count, or FAB subtype. In conclusion, Bmi-1 expression could be an independent prognostic marker and useful tool to design therapy for the AML patients.

scholarly journals Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia

Blood ◽  
1994 ◽  
Vol 83 (6) ◽  
pp. 1603-1611 ◽  
Author(s):  
A Neubauer ◽  
RK Dodge ◽  
SL George ◽  
FR Davey ◽  
RT Silver ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Univariate Analysis ◽  
Bone Marrow Blast ◽  
Ras Mutations ◽  
Ras Genes ◽  
Oligonucleotide Hybridization ◽  
Acute Myeloid

Mutations of the N- and K-ras genes are the most frequent genetic aberrations in acute myeloid leukemia (AML) and their detection in preleukemic conditions such as the myelodysplastic syndrome (MDS) suggests a role in the earliest phases of leukemogenesis. Despite these observations, little is known about the clinical importance of ras mutations in AML. We studied the clinical impact of ras mutations in 99 patients with de novo AML. All patients were treated in two prospective multicenter trials. The polymerase chain reaction was used to amplify areas surrounding the codons 12, 13, and 61 of the three ras genes N-, K-, and H-ras from DNA from bone marrow cells, ras mutations were detected by an algorithm based on allele-specific oligonucleotide hybridization. Eighteen of 99 (18%) patients harbored mutations in either N- or K-ras. All of the observed mutations occurred in N-ras (N = 10) and K-ras (N = 5) or concurrently in both N- and K-ras (N = 3). There were no significant differences between ras-negative and ras- positive patients according to age, sex, blood counts, cytogenetic abnormalities, or French-American-British classification. However, univariate analysis suggested a longer survival in ras-positive patients (P = .11). When adjusted for age, which was the most important factor affecting outcome, the presence of a ras mutation emerged as a significant predictor for improved survival (P = .03) and along with lower bone marrow blast counts (P = .02) and better cytogenetic category (P = .01). However, the presence of an aberrant ras allele was strongly correlated with lower bone marrow blast counts (P = .007). Thus, whether a mutation in the N-ras or K-ras proto-oncogenes directly affects treatment outcome or indirectly through an association with lower leukemic burden remains to be determined. Nevertheless, these findings counter the prevailing bias that oncogene mutations lead to more aggressive behavior in human malignancies.

scholarly journals Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia

Blood ◽  
1994 ◽  
Vol 83 (6) ◽  
pp. 1603-1611 ◽  
Author(s):  
A Neubauer ◽  
RK Dodge ◽  
SL George ◽  
FR Davey ◽  
RT Silver ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Univariate Analysis ◽  
Bone Marrow Blast ◽  
Ras Mutations ◽  
Ras Genes ◽  
Oligonucleotide Hybridization ◽  
Acute Myeloid

Abstract Mutations of the N- and K-ras genes are the most frequent genetic aberrations in acute myeloid leukemia (AML) and their detection in preleukemic conditions such as the myelodysplastic syndrome (MDS) suggests a role in the earliest phases of leukemogenesis. Despite these observations, little is known about the clinical importance of ras mutations in AML. We studied the clinical impact of ras mutations in 99 patients with de novo AML. All patients were treated in two prospective multicenter trials. The polymerase chain reaction was used to amplify areas surrounding the codons 12, 13, and 61 of the three ras genes N-, K-, and H-ras from DNA from bone marrow cells, ras mutations were detected by an algorithm based on allele-specific oligonucleotide hybridization. Eighteen of 99 (18%) patients harbored mutations in either N- or K-ras. All of the observed mutations occurred in N-ras (N = 10) and K-ras (N = 5) or concurrently in both N- and K-ras (N = 3). There were no significant differences between ras-negative and ras- positive patients according to age, sex, blood counts, cytogenetic abnormalities, or French-American-British classification. However, univariate analysis suggested a longer survival in ras-positive patients (P = .11). When adjusted for age, which was the most important factor affecting outcome, the presence of a ras mutation emerged as a significant predictor for improved survival (P = .03) and along with lower bone marrow blast counts (P = .02) and better cytogenetic category (P = .01). However, the presence of an aberrant ras allele was strongly correlated with lower bone marrow blast counts (P = .007). Thus, whether a mutation in the N-ras or K-ras proto-oncogenes directly affects treatment outcome or indirectly through an association with lower leukemic burden remains to be determined. Nevertheless, these findings counter the prevailing bias that oncogene mutations lead to more aggressive behavior in human malignancies.

Clinical Characteristics, Outcomes and Prognostic Factors for Patients with Acute Myeloid Leukemia Admitted to Intensive Care Settings

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4320-4320
Author(s):  
Shari A. Ghanny ◽  
C. Tom Kouroukis
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Intensive Care ◽  
Myeloid Leukemia ◽  
Care Setting ◽  
De Novo ◽  
Univariate Analysis ◽  
Medical Conditions ◽  
Intensive Care Setting ◽  
Acute Myeloid

Abstract Abstract 4320 Introduction Acute myeloid leukemia (AML) is a life-threatening, hematological malignancy that is characterized by a rapid clonal proliferation of myeloblasts. Patients with AML often present with compromised bone marrow function, increasing their risk for treatment-related morbidity and mortality, which may be complicated by patient-related factors such as age and co-morbid medical conditions. The objectives of our study were to determine the clinical characteristics, outcomes and prognostic factors of patients with acute myeloid leukemia (AML) admitted to intensive care settings (intensive care unit ICU or coronary care unit CCU). Methods We conducted a retrospective chart analysis of patients diagnosed and treated for AML at Hamilton Health Sciences (in Hamilton, Ontario, Canada) between January 2004-December 2011. Inpatients admitted to hospital were included in the analysis. We included patients with de novo, secondary and relapsed AML. Treatment for AML included: induction or consolidation chemotherapy, palliative and supportive measures. All patients admitted to intensive care settings were age (within three years) and gender matched to a control group of 24 patients with AML who did not require admission to an intensive care setting. We also looked at the number of co-morbid medical conditions between the two groups. Results A total of 115 patient charts were analyzed retrospectively. 24 patients (20.8%) required ICU/CCU admission during their treatment for AML. 11 patients (46%) were male. The most common reason for admission to an intensive care setting was respiratory distress (79.1%). The majority of patients requiring admission had de novo AML (66.7%) with intermediate risk cytogenetics (63.6%). Of the 24 patients requiring admission to an intensive care setting, 9 patients (37.5%) did not survive to be discharged from hospital. All of the remaining 15 patients survived at least 30 days post discharge from hospital. Using univariate analysis, white blood cell count (WBC) at diagnosis (p=0.01), type of AML (p=0.002), AML treatment (p=0.001) and admission to an intensive care setting (p=0.032) affected overall survival for the entire cohort. Using multivariate analysis, WBC at diagnosis (hazard ratio 1.007; 95% CI 1.002 to 1.012) and type of AML (hazard ratio for the comparison of denovo AML vs other categories is 0.059; 95% CI 0.009 to 0.367) affected overall survival. Using univariate analysis, denovo AML vs other types of AML (p=0.04) and percentage of peripheral blood blasts at diagnosis (borderline p=0.06) predicted admission to an intensive care setting. The number of co-morbid medical conditions did not predict admission to an intensive care setting. Conclusions The majority of AML patients do not require admission to an intensive care setting, however, the mortality rate of AML patients admitted to an intensive care setting is high. In this small retrospective dataset admission to an intensive care setting was associated with a significant difference in overall survival, but despite admission, long term survival is possible (overall survival for entire cohort 75%). Also, although a number of factors were significant on univariate analysis, (WBC at diagnosis, intensive care setting admission, type and treatment of AML), on multivariate analysis the only factors affecting overall survival were WBC at diagnosis and the type of AML. Type of AML predicted admission to an intensive care setting, there was no significant effect of the number of co-morbid medical conditions on admission to an intensive care setting. Disclosures: No relevant conflicts of interest to declare.

AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5352-5361 ◽  
Author(s):  
Jih-Luh Tang ◽  
Hsin-An Hou ◽  
Chien-Yuan Chen ◽  
Chieh-Yu Liu ◽  
Wen-Chien Chou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Remission Rate ◽  
Adult Patients ◽  
Poor Prognostic Factor ◽  
The Impact ◽  
Runx1 Mutation ◽  
Acute Myeloid

AbstractSomatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.

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