Monoallelic CEBPA mutations in normal karyotype acute myeloid leukemia: independent favorable prognostic factor within NPM1 mutated patients

2012 ◽  
Vol 91 (7) ◽  
pp. 1051-1063 ◽  
Author(s):  
Annika Dufour ◽  
◽  
Friederike Schneider ◽  
Eva Hoster ◽  
Tobias Benthaus ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Normal Karyotype ◽  
Favorable Prognostic Factor ◽  
Cebpa Mutations ◽  
Acute Myeloid

NPM1, IDH1/2 and DNAH11 Gene Mutations Can Improve a Prognostic Stratification of Acute Myeloid Leukemia Patients with Normal Karyotype but Not Harboring FLT3/ITD Mutation.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2534-2534
Author(s):  
Yeo-Kyeoung Kim ◽  
Il-Kwon Lee ◽  
Dennis Dong Hwan Kim ◽  
Chul Won Jung ◽  
Jun-Ho Jang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Normal Karyotype ◽  
Adult Patients ◽  
Npm1 Mutation ◽  
Group 3 ◽  
Group 2 ◽  
Acute Myeloid ◽  
Group 1

Abstract Abstract 2534 Background: Acute myeloid leukemia with normal karyotype (AML-NK) is known to be heterogeneous in the molecular level. Accordingly, it has become more critical to dissect this group of patients according to their prognosis using a molecular genetic technology. We attempted to analyze the incidence and prognostic implication of genetic abnormalities on survival in 426 adult patients with AML-NK. Methods: A total of 67 AML-NK patients achieved complete remission (CR), candidate mutations in 21 genes were identified by whole exome sequencing which has 41–89× coverage and by single-nucleotide polymorphism array analysis using marrow mononuclear cells at diagnosis of AML-NK. Subsequently, mutation analysis of 11 genes (i.e. FLT3/ITD, NPM1, DNMT3a, IDH1, IDH2, TET2, NRAS, WT1, DNAH11, SF3B1, and PHF6) which are known to be involved in the pathogenesis of hematologic diseases, were performed using Sanger sequencing in another subset of 359 AML-NK patients as a validation cohort. Results: Of 426 patients in total (median age: 51, ranges: 15–85), FLT3/ITD, NPM1, and DNMT3a mutations were associated with higher leukocytes counts at presentation of AML-NK. In 284 patients who received standard remission induction (RI) chemotherapy (excluding 119 patients with conservative treatment and 22 early death/1 follow-up loss after RI chemotherapy), those with FLT3/ITD mutation were significantly associated with a higher risk of relapse (p=0.02), a shorter leukemic-free survival duration (LFS)(p<0.01) or overall survival (OS) (p=0.01). Accordingly, we divided the patients into FLT3/ITD+ and FLT3/ITD− population, and analyzed their treatment outcomes according to the other mutations. In the FLT3/ITD− group (n=200), those with NPM1 mutation showed a higher CR rates after one or two cycles of RI chemotherapy (p<0.01) and a longer OS duration (p<0.01), hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.25–0.73, adjusted by other clinical variables including age, leukocyte counts at diagnosis, and transplantation (Figure 1). In the FLT3/ITD+ patients (n=84), NPM1 mutation was found to be a favorable prognostic factor showing a lower relapse rate (p=0.00), a longer LFS duration (p<0.01, HR 0.35, 95% CI 0.18–0.70), and OS duration (p=0.04, HR 0.55, 95% CI 0.31–0.98) in NPM1 mutated patients. In addition, OS was significantly different in favor of those with IDH2, especially R140Q IDH2 mutation, (p=0.04, HR 0.30, 95% CI 0.09–0.99), whereas DNAH11 mutation was associated with inferior OS (p<0.01, HR 5.78, 95% CI 1.65–20.25). Accordingly, we stratified the FLT3/ITD+ patients into three subgroups according to the NPM1, IDH1/2 and DNAH11 mutation status, Group 1: NPM1 mutation and IDH1 or 2 mutations (n=16), Group 2: isolated DNAH11 mutation (n=4) and Group 3: all mutations were negative (n=64). The group 1 showed significantly better OS than group 2 (p<0.01, HR 16.90, 95% CI 3.48–82.15) or group 3 (p<0.01, HR 3.40, 95% CI 1.20–9.55) (Figure 2). In a subgroup analysis of younger patients less than 60 years of age, similar outcomes were also observed in favor of group 1 in terms of OS (data not shown). Conclusion: Our study confirmed that NPM1 mutation is an independent prognostic factor in adult patients with AML-NK not harboring FLT3/ITD mutation. In addition, several other genetic markers were identified as prognostic including IDH1/2 or DNAH11 mutations as well as NPM1 mutation in a subgroup of AML-NK patients with FLT3/ITD mutation. Disclosures: No relevant conflicts of interest to declare.

Characterization of CEBPA Mutations in Acute Myeloid Leukemia in Taiwan - Most Patients with CEBPA Mutations Have Biallelic Mutations and Show a Distinct Immunophenotype of the Leukemic Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4321-4321
Author(s):  
Liang In Lin ◽  
Chien Yuan Chen ◽  
Dong Tsamn Lin ◽  
You Chia Yeh ◽  
Hwei Fang Tien
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Topoisomerase Ii ◽  
Normal Karyotype ◽  
Leukemic Cells ◽  
Intermediate Risk ◽  
Hla Dr ◽  
Cebpa Mutations ◽  
Biallelic Mutations ◽  
Acute Myeloid

Abstract The transcription factor CCAAT/enhancer binding protein alpha (C/EBPa) encoded by the CEBPA gene, is crucial for the differentiation of immature granulocytes. Diminished or abnormal C/EBPa activity resulting from CEBPA gene mutations is widely known to contribute to the transformation of myeloid progenitors via reduction of their differentiation potential. The CEBPA mutations have been detected in approximately 7% of total acute myeloid leukemia (AML) and in 15% of those with intermediate-risk cytogenetics or those with normal karyotype. However, the age distribution of the patients with the CEBPA mutations and the immunophenotype of their leukemic cells are not known. Sequential studies of the CEBPA gene in AML patients are also limited. In this study, 104 patients with de novo acute myeloid leukemia (AML) were evaluated for the CEBPA mutation by direct sequencing. Excluding the silent mutations, 16 (15%) of the total 104 AML patients, 15 (25%) of the 61 patients with intermediate-risk cytogenetics and 11 (35%) of the 31 patients with normal karyotype showed CEBPA mutations, frequencies higher than those reported in the West. Further cloning and subsequent nucleotide sequence analysis revealed that 14 patients had heterozygous biallelic mutations: 11 had mutations involving both the N-terminal transactivation domain (TAD) and the C-terminal basic leucine zipper domain (bZIP) and three, in either the TAD region or the bZIP region. The remaining two patients had only one allele mutation in the TAD1 region. Most mutations in TAD region were repeat-number changes of simple sequence repeats and those in bZIP region were internal tandem duplications. Sequence analysis revealed that in the region spanning the bZIP mutations, there was hot spot for concensus topoisomerase II sites, which has also been shown in other AML-related mutations FLT3-ITD and MLL duplication. All but one patient with CEBPA mutations had M1 or M2 subtype of AML. The patients with CEBPA mutations had significantly higher incidences of CD7 (73%), CD15 (100%), CD34 (93%) and HLA-DR (93%) expression than others and the majority of them showed a distinct immunophenotype of the leukemic cells: HLA-DR+ CD7+ CD13+ CD14− CD15+ CD33+ CD34+. The incidence of the CEBPA mutation in children with AML was similar to that in adults. The CEBPA mutation was serially analyzed in 27 patients; the mutations disappeared at CR, but reappeared at relapse. No one developed novel mutation during the follow-up period. In conclusion, the CEBPA mutation may play an important role in the development, but not progression, of AML. The patients with the CEBPA mutations showed a distinct immunophenotype of the leukemic cells. Potential topoisomerase II cleavage sites locating in the bZIP region were first reported and we propose that this is relevant to the process of illegitimate recombination generating the internal tandem duplication pattern of bZIP mutations.

Clinical Relevance of Concomitant Gene Mutations in CEBPA Double-Mutated Acute Myeloid Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2400-2400
Author(s):  
Vera Grossmann ◽  
Susanne Schnittger ◽  
Niroshan Nadarajah ◽  
Sandra Weissmann ◽  
Annette Fasan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Outcome ◽  
Survival Data ◽  
Myeloid Leukemia ◽  
Melting Curve ◽  
454 Sequencing ◽  
Normal Karyotype ◽  
Equity Ownership ◽  
Cebpa Mutations ◽  
Acute Myeloid

Abstract Abstract 2400 Background: CEBPA mutations occur in 5–14% of patients with acute myeloid leukemia (AML). A difference in clinical outcome between single- (sm) and double-mutated (dm) cases has been reported, whereupon dm cases were shown to be associated with longer overall (OS) and event-free survival (EFS). Aims: 1. Determine the frequency and clinical impact of CEBPA sm and dm in a large AML cohort. 2. Evaluate the spectrum of additional molecular mutations in CEBPA dm AML and their prognostic influence. Patients and Methods: First, we investigated CEBPA mutations in a cohort of 997 AML cases (462 female, 535 male; median age: 66.8 years) by 454 deep-sequencing (454 Life Sciences, Branford, CT). The cohort included: t(15;17)(q22;q12) n=33; t(8;21)(q22;q22) n=39; inv(16)(p13q22) n=31; normal karyotype (NK) n=447; complex karyotype (CK) (≥4 abnormalities) n=116; other abnormalities n=331. Second, we investigated an additional cohort of 111 AML dm CEBPA cases for mutations in ASXL1, DNMT3A, FLT3-ITD, FLT3-TKD, GATA2, IDH1/2, KRAS, MLL-PTD, NPM1, NRAS, RUNX1, TET2, TP53, and WT1 using 454 sequencing, Sanger sequencing, conventional PCR and melting curve analyses. This cohort was composed of 60 female and 51 male cases; median age: 62.3 years; 76 cases showed NK, 19 aberrant karyotype (n=4 n.a.). Survival data was available in 90/111 (81.1%) cases. Results: 1. In total, CEBPA mutations were detected in 75/997 (7.5%) of cases (t(15;17)(q22;q12) n=2/33; NK n=52/447; CK n=1/116; other abnormalities n=20/331). Of the 75 patients with CEPBA mutations 31 (41.3%) were sm, while 44 (58.7%) were dm. Patients with dm CEPBA showed better outcome compared to sm cases (OS at 3 yrs: 78.9% vs 38.5%, P=0.014; EFS after 3 yrs: 53.9% vs 36.6%, P=0.108). OS and EFS of CEBPA sm cases were comparable to CEPBA wt cases (OS at 3 yrs: 38.5% and 43.6%, P=0.689, EFS at 3 yrs: 36.6% and 29.4%, P=0.678). OS of CEBPA dm cases was comparable to patients with t(15;17)(q22;q12) (OS after 3 yrs: 78.9% vs 86.1%, P=0.597). 2. In the cohort of 111 patients we detected 227 CEBPA mutations. In 106 (95.5%) cases two mutations, and in 5 (4.5%) cases three mutations were detected. The median mutation load was 42% (range: 2–98%). The majority of mutations were frame-shift (n=135) and in-frame (n=66). Further, missense (n=19) and nonsense (n=7) mutations were observed. Most cases showed one N- and one C-terminal mutation (92/111, 82.8%), 10 (9.0%) cases harbored two N-terminal mutations, and 4 (3.6%) cases showed two C-terminal mutations. In addition, two cases showed one N- and two C-terminal mutations, two cases two N- and one C-terminal mutations, and one case harbored three N-terminal mutations. In 92/111 (82.9%) cases we observed at least one additional mutation (mean: 1.6 mutations; range: 1–4): TET2 39/109 (35.8%), ASXL1 20/111 (18.0%), GATA2 20/111 (18.0%), WT1 14/111 (12.6%), DNMT3A 11/109 (10.1%), IDH1/2 9/111 (8.1%) (IDH1 n=2, IDH2 n=7), NRAS 9/111 (8.1%), RUNX1 7/111 (6.3%), FLT3-ITD 7/111 (6.3%), KRAS 4/109 (3.7%), NPM1 3/111 (2.7%), FLT3-TKD 2/110 (1.8%), MLL-PTD 1/111 (1.0%), and TP53 1/110 (1.0%). With respect to clinical outcome we observed no differences in OS for concomitant mutations in DNMT3A, FLT3-ITD, IDH1/2, NRAS, TET2 and WT1. Cases with additional GATA2 mutations showed longer survival than wt cases (OS at 3 yrs: 100% versus 73.4%, P=0.026, EFS at 3 yrs: 67.5% versus 48.5%, P=0.137). In contrast, cases harboring additional ASXL1 or RUNX1 mutations were associated with worse outcome (ASXL1: OS at 3 yrs: 32.8% versus 85.7%, P<0.001, EFS at 3 yrs: 0% versus 57.9%, P=0.002; RUNX1: OS at 3 yrs: 0% versus 81.8%, P=0.001, EFS at 3 yeaers: 0% versus 53.8%, P=0.003). Since mutations in ASXL1 and RUNX1 frequently occurred concomitantly, they were grouped together (n=21). When then separating cases into (1) GATA2 mut, (2) GATA2 wt, ASXL1wt, RUNX1wt and (3) ASXL1mut and/or RUNX1mut we observed 3 distinct survival curves (OS at 3 yrs: 100% vs 81.2% vs 32.8, P<0.001, EFS at 3 yrs: 67.5% and 55.3% and 0%, P=0.005). No statistical analysis was performed for FLT3-TKD, KRAS, MLL-PTD, NPM1, TP53 due to the low number of mutations. Conclusions: 1. In CEBPA dm cases a high frequency of concomitant mutations (82.9%) was observed. 2. Most common mutated genes were TET2 (35.8%), ASXL1 (18.0%), GATA2 (18.0%), WT1 (12.6%), DNMT3A (10.1%), and RUNX1 (6.3%). 3. In CEBPA dm cases GATA2 mutations were associated with longer OS, whereas OS was poor in ASXL1 and/or RUNX1 mutated cases. Disclosures: Grossmann: MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership. Nadarajah:MLL Munich Leukemia Laboratory: Employment. Weissmann:MLL Munich Leukemia Laboratory: Employment. Fasan:MLL Munich Leukemia Laboratory: Employment. Eder:MLL Munich Leukemia Laboratory: Employment. Stopp:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.

ERG Expression Is an Independent Prognostic Factor and Allows Refined Risk Stratification in Cytogenetically Normal Acute Myeloid Leukemia: A Comprehensive Analysis of ERG, MN1, and BAALC Transcript Levels Using Oligonucleotide Microarrays

2009 ◽  
Vol 27 (30) ◽  
pp. 5031-5038 ◽  
Author(s):  
Klaus H. Metzeler ◽  
Annika Dufour ◽  
Tobias Benthaus ◽  
Manuela Hummel ◽  
Maria-Cristina Sauerland ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Oligonucleotide Microarrays ◽  
Prognostic Information ◽  
Transcript Levels ◽  
Expression Levels ◽  
Positive Correlations ◽  
Cebpa Mutations ◽  
Acute Myeloid

Purpose Recently, several novel molecular prognostic markers were identified in cytogenetically normal acute myeloid leukemia (CN-AML). In addition to the well-known influence of FLT3, NPM1, and CEBPA mutations, high transcript levels of the ERG, BAALC, and MN1 genes have been associated with inferior outcomes, but the relative importance of these risk markers remains to be defined. Patients and Methods We analyzed ERG, BAALC, and MN1 expression levels in a cohort of 210 patients with CN-AML who received intensive chemotherapy. Expression levels of ERG, BAALC, and MN1 were determined in bone marrow samples by using oligonucleotide microarrays. Results High transcript levels of ERG, BAALC, and MN1 were predictors for inferior overall survival (OS) and a lower rate of complete remissions (CRs). There were significant positive correlations between the expression levels of all three genes. ERG expression levels predicted OS in elderly patients (ie, age 60 years or older) with CN-AML (P = .006) as well as in younger patients (P = .013). In multivariate analyses, high ERG expression was independently associated with a lower CR rate (P = .013), shorter event-free survival (P = .008), and shorter OS (P = .005). Patients who had low ERG levels and absent FLT3 internal tandem duplication (ITD) had a 5-year OS of 44%, and patients who had high ERG expression and FLT3 ITD had a 5-year OS of only 5%. Conclusion We analyzed a comprehensive set of molecular risk factors in a large, homogeneous CN-AML patient cohort. In this study, high ERG expression levels emerged as a strong negative prognostic factor and provided prognostic information in addition to established molecular markers.

scholarly journals CIP2A high expression is a poor prognostic factor in normal karyotype acute myeloid leukemia

Haematologica ◽  
2015 ◽  
Vol 100 (5) ◽  
pp. e183-e185 ◽  
Author(s):  
E. Barragan ◽  
M. C. Chillon ◽  
R. Castello-Cros ◽  
N. Marcotegui ◽  
M. I. Prieto ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Normal Karyotype ◽  
High Expression ◽  
Poor Prognostic Factor ◽  
Acute Myeloid

Mutation of the Wilms’ Tumor 1 Gene Is a Poor Prognostic Factor Associated With Chemotherapy Resistance in Normal Karyotype Acute Myeloid Leukemia: The United Kingdom Medical Research Council Adult Leukaemia Working Party

2008 ◽  
Vol 26 (33) ◽  
pp. 5429-5435 ◽  
Author(s):  
Priya Virappane ◽  
Rosemary Gale ◽  
Robert Hills ◽  
Ioannis Kakkas ◽  
Karin Summers ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Wilms Tumor ◽  
Normal Karyotype ◽  
Npm1 Mutation ◽  
Poor Prognostic Factor ◽  
Exon 9 ◽  
Wilms Tumor 1 ◽  
Acute Myeloid

Purpose To determine the clinical relevance of Wilms’ tumor 1 (WT1) gene mutations in acute myeloid leukemia (AML) with normal karyotype (NK). Patients and Methods Exons 7 and 9 of WT1 were screened in samples from 470 young adult NK AMLs using a combination of direct sequencing and high-resolution capillary electrophoresis. Results Overall, 51 mutations were detected in 47 cases (10%): 46 frameshift mutations with insertion/deletion of one to 28 base pairs in exon 7 (n = 45) or exon 9 (n = 1), with a median mutant level of 45% (range, 8% to 86%), and five substitutions in exon 9: D396N (n = 3), H397Y (n = 1) and H397Q (n = 1). Patients with WT1 mutations had an inferior response to induction chemotherapy compared with wild-type cases (complete remission rate, 79% v 90%, odds ratio [OR] = 3.02; 95% CI, 1.17 to 7.82; P = .02), a higher rate of resistant disease (15% v 4%; OR = 9.33; 95% CI, 2.38 to 36.6; P = .001), an increased cumulative incidence of relapse (67% v 43%, hazard ratio [HR] = 3.02; 95% CI, 1.69 to 5.38; P = .0008), with a reduction in both relapse-free survival (22% v 44%; HR = 2.16; 95% CI, 1.32 to 3.55; P = .005) and overall survival (26% v 47%; HR = 1.91; 95% CI, 1.23 to 2.95; P = .007) at 5 years. In multivariate analysis, which included FLT3 internal tandem duplication and NPM1 mutation status, the presence of a WT1 mutation remained an independent adverse prognostic factor. Conclusion WT1 mutations are a negative prognostic indicator in NK AML and may be suitable for the development of targeted therapy.

Genome-Wide Single-Nucleotide Polymorphism-Array Based Karyotyping Detects Clonal Aberrations Including Uniparental Disomy (UPD), Gain or Loss Which Were Unfavorable Prognostic Factor In Acute Myeloid Leukemia with Normal Karyotype.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1669-1669
Author(s):  
Dong Hwan (Dennis) Kim ◽  
Jungwon Huh ◽  
Boram Han ◽  
Ha Yeon Lee ◽  
Jun Ho Yi ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Normal Karyotype ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Unfavorable Prognostic Factor ◽  
Genome Wide ◽  
Acute Myeloid

Abstract Abstract 1669 Background: Acute myeloid leukemia (AML) with normal karyotype (NK) comprises of 40–50% in overall AML population, presenting diverse and heterogeneous clinical behavior and prognosis. Recent study by Tiu et al (JCO 2009, 27(31); 5219-26) presented that new lesions detected by genome-wide single nucleotide polymorphism arrays (SNP-A) based karyotyping represent worse prognosis in 140 AML patients including 50 patients with AML-NK. The current study investigated diagnostic and prognostic role of SNP-A based karyotying in 100 patients with AML-NK treated with homogeneous treatment protocol. Methods and materials: A total of 100 patients with AML-NK confirmed by cytogenetic analysis and FISH analysis included in this study. All of the patients were diagnosed as AML-NK between 1998 and 2009 and received idarubicin plus cytarabine 3+7 induction chemotherapy at 4 hospitals in Korea. Genome-Wide Human SNP 6.0 Array (Affymetrix, CA, USA) was performed using DNAs derived from marrow samples taken at the time of diagnosis. Genotyping Console version 3.1 software was used for SNP-A karyotyping analysis. Results: In overall patients, complete remission (CR) rate was 89%, and the 2-years' rate of EFS and OS was 56.6±5.6% and 63.2±5.5%, respectively. The median duration of EFS and OS was 32.7 months and 76.6 months. Ninty-six clonal aberrations (CAs) were identified in 34 patients (34%) which were not detected by metaphase cytogenetics which were normal karyotype. These CAs included 44 losses at 17q, 17p, 7q, 11p, 1p, 5q, 6q, 7p, and 19p; 23 gains at chromosome 8, 9p, 15q, 17p, 17q, 21q, and 22q; and 29 uniparental disomies (UPDs) at 13q, 11p, 11q, 19q, 21q and 22q. When analyzed the CR rate according to the presence of CAs, no association was noted between the group with and without CAs (91% vs 87%; p=0.6). With respect to EFS, the group with CAs showed worse 2-years' EFS rate than those without CAs (39.0±9.5% vs 64.9±6.6%; p=0.05). As regards to OS, the group with CAs showed worse 2-years' EFS rate than those without CAs (40.7±9.6% vs 73.7±6.4%; p=0.01). Multivariate analyses showed that the CAs detected by SNP-A karyotyping has unfavorable prognostic value for EFS (hazard ratio [HR] = 3.29; 95% CI, 1.70 to 6.37; P<0 .001) and OS (HR = 4.06; 95% CI, 1.93 to 8.56; P<0.001) together with other significant prognostic factors (age above 60 years and WBC counts over 100×109/L at presentation). Conclusion: Our data showed that 1) Ninty six CAs were detected in one third of patients with AML-NK, and that 2) CAs represent unfavorable prognostic factor, thus requiring further sophisticated treatment strategy including allogeneic stem cell transplantation and novel therapy. Overall and event free survival by the presence of clonal aberrations (CAs) detected by SNP-array karyotyping (dot: group without CAs/line: group with CAs) Disclosures: No relevant conflicts of interest to declare.

scholarly journals Lymphoid enhancer-binding factor 1 (LEF-1): a favorable prognostic factor in adult acute myeloid leukemia in Egyptian patients

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Botheina Ahmed Thabet Farweez ◽  
Nahela Ahmed Shalaby ◽  
Doaa Ahmed Gamal Eissa ◽  
Raghda El Sayed Abdel Monem Galal ◽  
Nashwa El-khazragy ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Binding Factor ◽  
Egyptian Patients ◽  
Favorable Prognostic Factor ◽  
Acute Myeloid

The Presence of FLT3/ITD Mutations Is an Independent Prognostic Factor in Acute Myeloid Leukemia Patients with Normal Karyotype.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3008-3008 ◽  
Author(s):  
Yeo-Kyeoung Kim ◽  
Je-Jung Lee ◽  
Yu-Ra Lee ◽  
Il-Kwon Lee ◽  
Hee-Nam Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Normal Karyotype ◽  
Intermediate Risk ◽  
Free Survival ◽  
Significant Difference ◽  
Acute Myeloid

Abstract An internal tandem duplication of the FLT3 gene (FLT3/ITD) has been detected in approximately 20–30% of patients with acute myeloid leukemia (AML). These are frequently associated with poor outcome in AML patients, but it is still a matter of debate whether the FLT3/ITD mutations play a role in the prognosis of AML patients independently or not. We investigated the presence of FLT3/ITD mutation in 165 patients with de novo AML, except acute promyelocytic leukemia (APL), to evaluate its clinical and prognostic significance. The FLT3/ITD mutations were studied on bone marrow samples at diagnosis using PCR assay. Of the patients, 58 patients (35.2%) demonstrated the aberrant FLT3/ITD mutations. The patients with FLT3/ITD had significantly higher WBC counts at presentation compared with patients without FLT3/ITD (52.9 ± 66.9 ×109/L vs. 32.4 ± 41.8 ×109/L, p &lt; 0.05). However, there was no statistically significant difference in age, gender, hemoglobin level, platelet count, percentage of peripheral or bone marrow blasts, or the presence of molecular abnormalities between the patients with FLT3/ITD and the patients without FLT3/ITD. To analyze the response to or outcome of therapy, we evaluated 118 patients who received intensive induction chemotherapy. In univariate analysis, there was no significant difference in complete response rate (p = 0.21), in median duration of overall survival (13.9±3.8 ms. vs. 16.5±0 ms., p = 0.07), or in median duration of leukemic-free survival (LFS) (9.8±3.5 ms. vs. 34.6±17.9 ms., p = 0.09) between the patients with FLT3/ITD and the patients without FLT3/ITD. However, the presence of FLT3/ITD was associated with lower LFS in the patients with a cytogenetically intermediate-risk group (p &lt; 0.05). Furthermore, in multivariate analysis, FLT3/ITD mutations were an independent prognostic factor in LFS in AML patients with normal karyotype (p &lt; 0.05). In conclusion, this study demonstrates that the presence of FLT3/ITD mutations is a significantly poor prognostic factor for leukemic free survival in non-APL patients with a cytogenetically intermediate-risk group, especially normal karyotype.

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