scholarly journals Long Noncoding RNA Maternally Expressed Gene 3 Is Downregulated, and Its Insufficiency Correlates With Poor-Risk Stratification, Worse Treatment Response, as Well as Unfavorable Survival Data in Patients With Acute Myeloid Leukemia

2020 ◽  
Vol 19 ◽  
pp. 153303382094581
Author(s):  
Chunling He ◽  
Xinmei Wang ◽  
Jing Luo ◽  
Yinghua Ma ◽  
Zhen Yang
Keyword(s):  
Acute Myeloid Leukemia ◽  
Long Noncoding Rna ◽  
Myeloid Leukemia ◽  
Noncoding Rna ◽  
Event Free Survival ◽  
Free Survival ◽  
Healthy Donors ◽  
Low Expression ◽  
Maternally Expressed Gene 3 ◽  
Acute Myeloid

Objective: Our study aimed to investigate the correlation of long noncoding RNA maternally expressed gene 3 expression with clinical features, treatment response, and survival profiles in patients with acute myeloid leukemia. Methods: Bone marrow samples of 122 de novo patients with acute myeloid leukemia (prior to treatment) and 30 healthy donors (after enrollment) were collected, and long noncoding RNA maternally expressed gene 3 expression was detected by reverse transcription quantitative polymerase chain reaction. According to median value of long noncoding RNA maternally expressed gene 3 expression in patients with acute myeloid leukemia, they were divided into long noncoding RNA maternally expressed gene 3 high expression and low expression patients (which were further categorized as low---, low--, and low- expression patients). Results: Long noncoding RNA maternally expressed gene 3 expression was decreased in patients with acute myeloid leukemia compared to healthy donors. Besides, receiver operating characteristic curve displayed that long noncoding RNA maternally expressed gene 3 distinguished patients with acute myeloid leukemia from healthy donors. In patients with acute myeloid leukemia, long noncoding RNA maternally expressed gene 3 low expression was associated with poor-risk stratification but was not correlated with age, gender, French-American-Britain classification, or white blood cell level. For prognosis, complete remission rate was lowest in long noncoding RNA maternally expressed gene 3 low--- expression patients, followed by long noncoding RNA maternally expressed gene 3 low-- expression patients, long noncoding RNA maternally expressed gene 3 low- expression patients, and was highest in long noncoding RNA maternally expressed gene 3 high expression patients; Kaplan-Meier curves displayed that lower long noncoding RNA maternally expressed gene 3 expression was associated with reduced event-free survival and overall survival; Cox regression analysis showed that lower long noncoding RNA maternally expressed gene 3 expression independently predicted decreased event-free survival and worse overall survival in patients with acute myeloid leukemia. Conclusion: Long noncoding RNA maternally expressed gene 3 may function as a novel marker for effective surveillance and management of acute myeloid leukemia.

Low Expression of Long Noncoding RNA IRAIN Is Associated with Poor Prognosis in Non-M3 Acute Myeloid Leukemia Patients

2018 ◽  
Vol 22 (5) ◽  
pp. 288-294 ◽  
Author(s):  
Hossein Pashaiefar ◽  
Marzieh Izadifard ◽  
Marjan Yaghmaie ◽  
Maryam Montazeri ◽  
Elahe Gheisari ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Long Noncoding Rna ◽  
Myeloid Leukemia ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
Low Expression ◽  
Acute Myeloid

scholarly journals Effect of Diagnosis (Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation, or Acute Myeloid Leukemia [AML]) on Outcome of AML-Type Chemotherapy

Blood ◽  
1997 ◽  
Vol 90 (8) ◽  
pp. 2969-2977 ◽  
Author(s):  
Elihu Estey ◽  
Peter Thall ◽  
Miloslav Beran ◽  
Hagop Kantarjian ◽  
Sherry Pierce ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Multivariate Analyses ◽  
Patient Characteristics ◽  
Refractory Anemia ◽  
Event Free Survival ◽  
Free Survival ◽  
Current Medical Practice ◽  
Acute Myeloid

Abstract In current medical practice, patients with refractory anemia with excess blasts in transformation (RAEB-t), and especially patients with RAEB, receive chemotherapy regimens (AML Rx) administered to patients with acute myeloid leukemia (AML) less often than do patients with AML. These entities are distinguished primarily by marrow blast percentage (5% to 19% RAEB, 20% to 29% RAEB-t, and ≥30% AML). The poor prognosis of many RAEB or RAEB-t patients, if untreated, led us to give them AML Rx using the same plan as for AML. The purpose of this analysis was to see if diagnosis (RAEB, RAEB-t, or AML) affected outcome. We treated 372 patients with AML (acute promyelocytic leukemia [APL] excluded), 106 with RAEB-t, and 52 with RAEB. AML Rx produced a 62% complete remission (CR) rate in RAEB, essentially identical to the rates in RAEB-t and AML, but event-free survival (EFS) from CR and from start of treatment (start of Rx), as well as overall survival, were poorer in RAEB than in AML or RAEB-t, with AML and RAEB-t being identical. However, patients with RAEB or RAEB-t were more likely to have poor prognostic characteristics, in particular complex abnormalities involving chromosomes 5 and/or 7. Multivariate analyses indicated that, when considered together with cytogenetics and other patient characteristics, a diagnosis of RAEB rather than AML or RAEB-t had no effect on EFS from start of Rx, EFS from CR, survival, or achievement of CR. These analyses suggested a trend for patients with RAEB-t to have better EFS from start of Rx than patients with AML or RAEB (P = .08; relative risk, 0.80; 95% confidence interval, 0.62 to 1.03), but there were no differences with respect to the other outcomes. Our data suggest that the propriety of administering AML Rx to patients with RAEB or RAEB-t who have poor prognosis without treatment is identical to the propriety of treating AML in this fashion. Deterrents to standard AML Rx in these patients could justifiably include cytogenetics, age, etc, but not a diagnosis of RAEB or RAEB-t per se.

scholarly journals Allogeneic Stem Cell Transplant for Acute Myeloid Leukemia: Evolution of an Effective Strategy in India

2017 ◽  
Vol 3 (6) ◽  
pp. 773-781 ◽  
Author(s):  
Abhijeet Ganapule ◽  
Sandeep Nemani ◽  
Anu Korula ◽  
Kavitha M. Lakshmi ◽  
Aby Abraham ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Cost Effectiveness ◽  
Myeloid Leukemia ◽  
Cost Effective ◽  
Effective Strategy ◽  
Event Free Survival ◽  
Myeloablative Conditioning ◽  
Free Survival ◽  
Acute Myeloid

Purpose There are limited data from developing countries on the role and cost-effectiveness of allogeneic stem cell transplantation (allo-SCT) for patients with acute myeloid leukemia (AML). Patients and Methods We undertook a retrospective descriptive study of all patients with AML who underwent allo-SCT from 1994 to 2013 at our center to evaluate the clinical outcomes and cost-effectiveness of this therapeutic modality. Results Two hundred fifty-four consecutive patients, median age 34 years, who underwent allo-SCT at our center were included in this study. There were 161 males (63.4%). The 5-year overall survival (OS) and event-free survival for the entire cohort was 40.1 ± 3.5% and 38.7 ± 3.4%, respectively. The 5-year OS for patients in first (CR1), second, and third complete remission and with disease/refractory AML was 53.1 ± 5.2%, 48.2 ± 8.3%, 31.2 ± 17.8%, and 16.0 ± 4.4%, respectively ( P < .001). From 2007, reduced intensity conditioning (RIC) with fludarabine and melphalan (Flu/Mel) was used in a majority of patients in CR1 (n = 67). Clinical outcomes were compared with historical conventional myeloablative conditioning regimens (n = 38). Use of Flu/Mel was associated with lower treatment-related mortality at 1 year, higher incidence of chronic graft-versus-host-disease, and comparable relapse rates. The 5-year OS and event-free survival for Flu/Mel and myeloablative conditioning group was 67.2 ± 6.6% versus 38.1 ± 8.1% ( P = .003) and 63.8 ± 6.4% versus 32.3 ± 7.9% ( P = .002), respectively. Preliminary cost analysis suggests that in our medical cost payment system, RIC allo-SCT in CR1 was likely the most cost-effective strategy in the management of AML. Conclusion In a resource-constrained environment, Flu/Mel RIC allo-SCT for AML CR1 is likely the most efficacious and cost-effective approach in a subset of newly diagnosed young adult patients.

scholarly journals MicroRNA Expression-Based Model Indicates Event-Free Survival in Pediatric Acute Myeloid Leukemia

2017 ◽  
Vol 35 (35) ◽  
pp. 3964-3977 ◽  
Author(s):  
Emilia L. Lim ◽  
Diane L. Trinh ◽  
Rhonda E. Ries ◽  
Jim Wang ◽  
Robert B. Gerbing ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Oxidative Phosphorylation ◽  
Treatment Failure ◽  
Myeloid Leukemia ◽  
Outcome Prediction ◽  
Classification Scheme ◽  
Event Free Survival ◽  
Free Survival ◽  
Pediatric Aml ◽  
Acute Myeloid

Purpose Children with acute myeloid leukemia (AML) whose disease is refractory to standard induction chemotherapy therapy or who experience relapse after initial response have dismal outcomes. We sought to comprehensively profile pediatric AML microRNA (miRNA) samples to identify dysregulated genes and assess the utility of miRNAs for improved outcome prediction. Patients and Methods To identify miRNA biomarkers that are associated with treatment failure, we performed a comprehensive sequence-based characterization of the pediatric AML miRNA landscape. miRNA sequencing was performed on 1,362 samples—1,303 primary, 22 refractory, and 37 relapse samples. One hundred sixty-four matched samples—127 primary and 37 relapse samples—were analyzed by using RNA sequencing. Results By using penalized lasso Cox proportional hazards regression, we identified 36 miRNAs the expression levels at diagnosis of which were highly associated with event-free survival. Combined expression of the 36 miRNAs was used to create a novel miRNA-based risk classification scheme (AMLmiR36). This new miRNA-based risk classifier identifies those patients who are at high risk (hazard ratio, 2.830; P ≤ .001) or low risk (hazard ratio, 0.323; P ≤ .001) of experiencing treatment failure, independent of conventional karyotype or mutation status. The performance of AMLmiR36 was independently assessed by using 878 patients from two different clinical trials (AAML0531 and AAML1031). Our analysis also revealed that miR-106a-363 was abundantly expressed in relapse and refractory samples, and several candidate targets of miR-106a-5p were involved in oxidative phosphorylation, a process that is suppressed in treatment-resistant leukemic cells. Conclusion To assess the utility of miRNAs for outcome prediction in patients with pediatric AML, we designed and validated a miRNA-based risk classification scheme. We also hypothesized that the abundant expression of miR-106a could increase treatment resistance via modulation of genes that are involved in oxidative phosphorylation.

scholarly journals Myeloid sarcoma is associated with superior event-free survival and overall survival compared with acute myeloid leukemia

Cancer ◽  
2008 ◽  
Vol 113 (6) ◽  
pp. 1370-1378 ◽  
Author(s):  
Apostolia-Maria Tsimberidou ◽  
Hagop M. Kantarjian ◽  
Sijin Wen ◽  
Michael J. Keating ◽  
Susan O'Brien ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Myeloid Sarcoma ◽  
Event Free Survival ◽  
Free Survival ◽  
Acute Myeloid

scholarly journals High Expression of Myocyte Enhancer Factor 2C (MEF2C) Is Associated with Adverse Risk Features and Poor Outcome in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2570-2570
Author(s):  
George S. Laszlo ◽  
Todd A. Alonzo ◽  
Chelsea J. Gudgeon ◽  
Kimberly H. Harrington ◽  
Alex Kentsis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Event Free Survival ◽  
Free Survival ◽  
Expression Levels ◽  
Acute Myeloid ◽  
Enhancer Factor

Abstract Background: Myocyte enhancer factor 2C (MEF2C) was initially identified as essential transcription factor for cardiac muscle development. However, subsequent studies have indicated that MEF2C plays a much broader biological role, including in the normal hematopoietic system. Recent studies have now identified MEF2C as cooperating oncogene in acute myeloid leukemia (AML) and suggested a contribution to the aggressive nature of at least some subtypes of AML. These findings raised the possibility that MEF2C could serve as marker of poor-risk disease and, therefore, have prognostic significance in AML. To test this hypothesis, we retrospectively quantified MEF2C expression in participants of the AAML0531 trial and correlated expression levels with disease characteristics and clinical outcome. Patients and Methods: AAML0531 (NCT00372593) was a multicenter phase 3 study that determined the addition of gemtuzumab ozogamicin to intensive chemotherapy among 1,022 eligible patients aged <30 yearswith newly diagnosed de novo non-APL AML, excluding those with bone marrow failure syndromes, juvenile myelomonocytic leukemia, or Down syndrome (if ≤3 years of age) between 2006 and 2010. Cryopreserved pretreatment ("diagnostic") specimens from patients enrolled on AAML0531 who consented to the biology studies and had bone marrow samples were available were included in this study. Total RNA from unsorted specimens was extracted, quantified, and subjected to quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) using TaqMan primers to determine expression of MEF2C and, for normalization, the housekeeping gene, β-glucuronidase (GUSB). Patient samples were run in duplicate, and the ΔΔCT method quantified as 2(-ΔΔCT) was used to determine the expression levels of MEF2C relative to GUSB. Results: In all 751 available patient specimens, MEF2C mRNA was detectable and varied >3,000-fold relative to GUSB (0.0091-29.1272 [median: 0.7978]). Patients with the highest relative MEF2C expression (4th quartile) less likely achieved a complete remission after one course of chemotherapy than the other patients (67% vs. 78%, P=0.005). They also had an inferior overall survival (P=0.014; at 5 years: 55±8% vs. 67±4%), inferior event-free survival (P<0.001; at 5 years: 38±7% vs. 54±4%), and higher relapse risk than patients within the lower 3 quartiles of MEF2C expression (P<0.001; at 5 years: 53±9% vs. 35±5%). Of note, exploratory multiple cutpoint analyses for overall and event-free survival indicated that the most statistically significant results were centered around the Q4 cutpoint region, supporting our approach of comparing patients with the highest quartile of relative MEF2C expression with those having lower relative MEF2C expression. Importantly, MEF2C expression was strongly associated with cytogenetic and molecular abnormalities. Specifically, patients with high MEF2C expression less likely had CBF translocations (inv(16): P=0.007, and t(8;21): P<0.001) or normal karyotype AML (P<0.001); conversely, they were more likely to have leukemia with monosomy 7 (P<0.001) and abnormalities involving 11q23 (P<0.001). Furthermore, patients with high MEF2C less likely had a FLT3/ITD (P =0.018) or a mutation in either NPM1 (P=0.010) or CEBPA (P =0.002). Consistently, patients with high MEF2C expression less likely had low-risk disease (16% vs. 46%, P<0.001) and more likely had standard-risk disease (68% vs. 42%, P <0.001) than those with lower MEF2C expression. Indeed, after adjustment for disease risk, age, FAB category, and treatment arm, high MEF2C expression was no longer statistically significantly associated with inferior overall survival (hazard ratio [HR]=0.99 [95% confidence interval: 0.72-1.36], P=0.929), inferior event-free survival (HR: 1.14 [0.86-1.49], P=0.365), or higher relapse risk (HR: 1.32 [0.91-1.92], P=0.137), suggesting that MEF2C cooperates with additional pathogenic abnormalities. Conclusion: High MEF2C expression identifies a subset of AML patients with adverse-risk disease features and poor outcome. These findings provide the rationale for therapeutic targeting of MEF2C transcriptional activation in AML. Disclosures Walter: AstraZeneca, Inc.: Consultancy; Covagen AG: Consultancy; Seattle Genetics, Inc.: Research Funding; Amgen, Inc.: Research Funding; Pfizer, Inc.: Consultancy; Amphivena Therapeutics, Inc.: Consultancy, Research Funding.

scholarly journals Acute Myeloid Leukemia Treatment Outcomes: First Report from Single Center Retrospective Study in Kazakhstan

2021 ◽  
Author(s):  
Jamilya Saparbay ◽  
Gulnara Kulkayeva ◽  
Vadim Kemaykin ◽  
Aset Kuttymuratov ◽  
Zhanna Burlaka ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Good Prognosis ◽  
Event Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is the most common hematological malignancy in adults. In the last decade, internationally approved AML treatment guidelines, including hematopoietic stem cell transplantation are widely used in Kazakhstan. The categorization of acute myeloid leukemia was done according to the French-American British classification. The prognosis of patients at the time of diagnosis was determined by cytogenetic tests following the guidelines of the European LeukemiaNet. The overall survival and event-free survival were analyzed using the Kaplan-Meier method, and hazard ratios were defined with Cox regression. Totally 398 patients with AML were treated in the National Research Oncology Center between 2010 and 2020. The mean age was 38.3 years. We have found the correlation between ethnicity, cytogenetic group, white blood cell count, and treatment approaches with overall and event-free survival. There was a significantly longer OS in a cytogenetic group with a good prognosis compared with intermediate and poor prognosis. The median survival time in the group with a good prognosis was 43 months, 23 months in the intermediate group (p=0.7), and 12 months in the poor prognosis group (p=0.016). There was a significantly longer OS for the group of patients who received hematopoietic stem cell transplantation (HSCT), 52 months versus 10 months in the group who received chemotherapy only, p-value < 0.0001. Prognostic factors, such as cytogenetic group, initial WBC count, and treatment approaches are significantly associated with patient survival. Our study data were consistent with previous reports.

Long noncoding RNA MIAT promotes the progression of acute myeloid leukemia by negatively regulating miR-495

2019 ◽  
Vol 87 ◽  
pp. 106265 ◽  
Author(s):  
Gaoyan Wang ◽  
Xuerong Li ◽  
Liang Song ◽  
Hua Pan ◽  
Jian Jiang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Long Noncoding Rna ◽  
Myeloid Leukemia ◽  
Noncoding Rna ◽  
Acute Myeloid

scholarly journals Pathologic Features of Down Syndrome Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Report From the Children's Oncology Group Protocol AAML0431

2019 ◽  
Vol 144 (4) ◽  
pp. 466-472 ◽  
Author(s):  
Kelley J. Mast ◽  
Jeffrey W. Taub ◽  
Todd A. Alonzo ◽  
Alan S. Gamis ◽  
Claudio A. Mosse ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Down Syndrome ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Event Free Survival ◽  
Diagnostic Features ◽  
Free Survival ◽  
Minimal Residual ◽  
Acute Myeloid

Context.— Detailed diagnostic features of acute myeloid leukemia in Down syndrome are lacking, leading to potential misdiagnoses as standard acute myeloid leukemia occurring in patients with Down syndrome. Objective.— To evaluate diagnostic features of acute myeloid leukemia and myelodysplastic syndrome in patients with Down syndrome. Design.— Diagnostic bone marrow samples from 163 patients enrolled in the Children's Oncology Group study AAML0431 were evaluated by using central morphologic review and institutional immunophenotyping. Results were compared to overall survival, event-free survival, GATA1 mutation status, cytogenetics, and minimal residual disease results. Results.— Sixty myelodysplastic syndrome and 103 acute myeloid leukemia samples were reviewed. Both had distinctive features compared to those of patients without Down syndrome. They showed megakaryocytic and erythroid but little myeloid dysplasia, and marked megakaryocytic hyperplasia with unusual megakaryocyte morphology. In acute myeloid leukemia cases, megakaryoblastic differentiation of blasts was most common (54 of 103, 52%); other cases showed erythroblastic (11 of 103, 11%), mixed erythroid/megakaryoblastic (20 of 103, 19%), or no differentiation (10 of 103, 10%). Myelodysplastic syndrome and acute myeloid leukemia cases had similar event-free survival and overall survival. Leukemic subgroups showed interesting, but not statistically significant, trends for survival and minimal residual disease. Cases with institutional diagnoses of French American British M1-5 morphology showed typical features of Down syndrome disease, with survival approaching that of other cases. Conclusions.— Myelodysplastic syndrome and acute myeloid leukemia in Down syndrome display features that allow discrimination from standard cases of disease. These distinctions are important for treatment decisions, and for understanding disease pathogenesis. We propose specific diagnostic criteria for Down syndrome–related subtypes of acute myeloid leukemia and myelodysplastic syndrome.

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