scholarly journals Comprehensive study on ERG gene expression in normal karyotype acute myeloid leukemia: ERG expression is of limited prognostic value, whereas the accumulation of adverse prognostic markers stepwise worsens the prognosis

2016 ◽  
Vol 6 (12) ◽  
pp. e507-e507 ◽  
Author(s):  
S Weber ◽  
T Haferlach ◽  
C Haferlach ◽  
W Kern
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Prognostic Markers ◽  
Normal Karyotype ◽  
Acute Myeloid ◽  
Comprehensive Study

NPM1 Mutated AML Is Associated With Lower Expression Of Poor Prognostic Markers BAALC, ERG and MN1 In Adult Patients With Acute Myeloid Leukaemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4945-4945 ◽  
Author(s):  
Poonkuzhali Balasubramanian ◽  
Ashok kumar Jayavelu ◽  
Ajay Abraham ◽  
Savitha Varatharajan ◽  
Sreeja Karathedath ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Markers ◽  
Normal Karyotype ◽  
Adult Patients ◽  
Rna Expression ◽  
Flt3 Mutations ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a clinically and biologically complex and heterogeneous hematopoietic neoplasm. Recent advances in acute myeloid leukemia (AML) biology have lead to prognosticate and predict treatment outcome in AML based on molecular markers. Mutations in NPM1, CEBPA are considered good prognosis and High BAALC, ERG & MN1 expression associate with worse outcome in AML patients treated with standard chemotherapy. Although many efforts have been made to identify genetic mutations and modulated gene expression levels that can be used to predict outcomes in patients with AML, the association between these prognostic markers has not been evaluated. We have reported previously that the NPM1 mutated patients have significantly high dCK and hENT1 gene expression (involved in cytarabine metabolism) and low ABCG2 and ABCB1transporter expression (Abraham et al, ASH abstracts; Nov 2011; 118: 3481 and Nov 2012; 120: 143), suggesting that the good prognostic nature of this mutation is possibly due to the better metabolism and transport of the chemotherapeutic drugs used in induction therapy.  We extended this study to look for association between NPM1/FLT3 mutation status and the RNA expression of other good or poor prognostic markers in patients with AML. We prospectively included 274 adult patients with AML in this study. The median age was 42 years (range 16-74y). AML was diagnosed according to the FAB and WHO classifications. There were 238 patients with de novo AML; Secondary AML -6; Therapy related AML- 2 and Relapsed AML-28. Bone marrow cytogenetics and immunophenotyping analysis was available for all patients at diagnosis and/or relapse. Diagnostic bone marrow MNCs were isolated by ficoll- density gradient centrifugation and stored in trizol reagent for RNA expression and mutation detection. RT-PCR was used to screen AML-ETO and Inv 16, and the expression of BAALC, ERG1, MN1, CXCR4 and WT1were analyzed using RQ-PCR. NPM1-c, FLT3 ITD and TKD were screened using DNA PCR followed by gene-scan, sequencing or RFLP methods. The basic demographics and the frequency of the markers are listed in Table 1. When analyzed separately in normal karyotype AML (NK-AML), the frequencies of the mutations were: NPM1: 52.2%; FLT3-ITD: 24%; TKD: 4.3%. When the RNA expression of BAALC, WT1, ERG1, CXCR4 and MN1 was compared in patients with NPM1 or FLT3 mutations, we noticed that patients with NPM1 had significantly low expression of BAALC, MN1 and ERG1 while those with FLT3 mutations (ITD or TKD) had higher expression of these genes (Figure1). There was no significant association with CXCR4 or WT1 expression and these mutations. When analyzed separately in the normal karyotype AML, these associations were still significant. In addition, the relapsed patients had significantly higher expression of BAALC, MN1, and ERG1 RNA compared to de-novoAML cases (data not shown). To conclude, we show that NPM1 or FLT3 mutations acquire the prognostic significance due to several factors including BAALC, ERG1 and MN1expression levels in addition to drug metabolizing enzymes’ and drug transporter expression. These factors must be taken into consideration when attempting to personalize chemotherapy in AML. Disclosures: No relevant conflicts of interest to declare.

Value of Gene Expression Profiling by Taqman® Low Density Arrays in the Diagnosis and Prognosis of Acute Myeloid Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1620-1620
Author(s):  
Carmen Chillon ◽  
Carlos Santamaria ◽  
Ramon Garcia-Sanz ◽  
Montserrat Hernandez ◽  
Norma C. Gutiérrez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Normal Karyotype ◽  
Low Density ◽  
Fusion Transcripts ◽  
11Q23 Abnormalities ◽  
Diagnostic And Prognostic Value ◽  
Acute Myeloid

Abstract Abstract 1620 Poster Board I-646 Background So far, none of the high-density microarray studies in acute myeloid leukemia (AML) have provided a useful approach with relevant diagnostic and prognostic value for the routine clinical practice. We aimed to assess the clinical utility of a small combination of genes and fusion genes included in a microfluidic card by means of real-time quantitative PCR (RQ-PCR) in AML patients. Patients and methods Ninety-six clinically relevant markers were analyzed simultaneously using TaqMan® Low Density Arrays (TLDAs) (Applied Biosystems, Foster City, CA). This plataform includes: 3 control genes (ABL1, GADPH and GUS), 36 AML specific fusion transcripts described, NPM1 mutations and 55 genes which RNA expression levels have been associated with prognosis or pathogenic process in AML. To assess the feasibility of the designed TLDA we evaluated the gene expression profile of 191 leukemia patients at diagnosis: 167 AML (inv(16): n=11, t(8;21): n=9, t(15;17): n=7, with 11q23 abnormalities: n=27, with other cytogenetic abnormalities: n=20 and normal karyotype n=93), 16 pre-B-ALL, 5 T-ALL and 3 CML with rare BCR-ABL fusions (b2a3, b3a3 and e19a2). Results We observed a high correlation between TLDA results for fusion transcripts and those obtained by gold standard techniques (RQ-PCR based on Europe against Cancer protocols). Indeed, we identified 89 patients with different fusion transcripts, including 18 cases previously reported as negative by cytogenetics or FISH approach. Patients with a favorable karyotype showed a distinctive gene expression profile. Thus, inv(16) AML overexpressed: MYH11, CLIP3, CTNNB1, SPARC, SNAI1 and MN1; t(8;21) AML expressed high levels of ETO, POU4F1, CAV1, CD34, FOXO3A, PRAME and BAALC, and t(15;17) AML showed upregulation of HGF, FGF13, WT1 and PRAME. Further, the 51 NPM1 mutated patients (38 A, 5 B, 6 D and 2 DD1, confirmed by sequencing) also showed a specific gene profile, showing high NPM1, CD34, ABCB1, ABCG2, BAALC, PROM1 or BCL2 RNA levels and low HOXA7, HOXA9 and MEIS1 RNA levels. In contrast, AML with 11q23 abnormalities or with FLT3-ITD mutations did not exhibit a characteristic pattern. Several genes (EVI1, BAALC, ERG, PRAME or PIM1) showed prognostic significance in AML with normal karyotype and AML with NPM1 mutations, thus confirming TLDA as a useful approach for risk assessment in AML. Interestingly, PIM1 overexpression was an independent predictor for shorter relapse-free (RFS) and overall survival (OS) in patients with normal karyotype (p=0.012 and p<0.001, respectively) and patients harboring NPM1 mutations (p=0.004 and p=0.002). Moreover, patients with FLT3-ITD mutations and high levels of PIM1 showed an extremely poor prognosis (2-year RFS 26% and OS 30%). These results were confirmed in multivariate analyses. Conclusions We showed the diagnostic and prognostic value of the designed TLDA platform for evaluation of AML patients. Furthermore, in our series PIM1 has been identified as the most important prognostic marker and thus this oncogene could be used for a more accurate risk classification of AML patients. Disclosures Gutiérrez: Janssen Cilag: Honoraria; Celgene: Honoraria. Díaz-Mediavilla:Janssen-Cilag: Honoraria; Celgene: Honoraria.

scholarly journals Prognostic value of CIP2A gene expression in adult Egyptian acute myeloid leukemia patients

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Roxan E. Shafik ◽  
Azza M. Ibrahim ◽  
Fadwa Said ◽  
Naglaa M. Hassan ◽  
Hanan E. Shafik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Acute Myeloid

RNA-Sequencing Unveils Cryptic Fusions in Patients with Acute Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1278-1278
Author(s):  
Fabiana Ostronoff ◽  
Matthew Fitzgibbon ◽  
Martin McIntosh ◽  
Rhonda E. Ries ◽  
Alan S. Gamis ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Rna Sequencing ◽  
Myeloid Leukemia ◽  
Prognostic Markers ◽  
Normal Karyotype ◽  
Fusion Transcript ◽  
Rna Seq ◽  
Illumina Hiseq ◽  
Normal Controls ◽  
Acute Myeloid

Abstract Abstract 1278 Introduction: Acute myeloid leukemia (AML) represents a heterogeneous group of malignancies with great variability in response to therapy. In recent years, an increasing list of molecular markers with prognostic significance in AML has been identified; nonetheless, new prognostic markers and therapeutic targets are still needed. The aim of this study was to identify and verify fusion transcripts using RNA-Sequencing (RNA-Seq) that would be otherwise undetectable by conventional karyotyping. Methods: Transcriptome Sequence data is generated by high-throughput short-read RNA-Seq performed for each AML sample on the Illumina HiSeq. Poly(A) RNA is captured with poly(T) magnetic beads, fragmented, copied to cDNA libraries with reverse transcriptase and random primers. Each library is subjected to 50-cycle paired-end sequencing on the Illumina HiSeq at Hudson Alpha. Filtered Fastq files are processed with TopHat-Fusion [Kim2011,Trapnell2009] alignment software to discover cryptic fusions in RNA-Seq data without relying on known, annotated models. This process yielded an average of 20 million alignable reads per sample. Cord blood blast cell transcripts are also processed and serve as normal controls. A series of filtering steps eliminate junctions commonly found to be in error. Filtered junctions found in at least 3 AML samples and no normal controls are retained as AML-associated candidate junctions. Visual curation of candidates is performed using Integrative Genomics Viewer. Candidate fusions were verified by RT-PCR amplification of the AML-associated fusions in the index cases. Fusion transcript product, as well as the break point junction was verified by Sanger sequencing Results: Diagnostic specimens from 70 patients with de novo AML that included patients with normal karyotype (NK, N=31), core-binding factor (CBF) AML (N=33) and other (N=6) were sequenced. Age at diagnosis varied from 10 months to 69 years (Median 12 years). White blood cell count (WBC) and blast percentage were 49×109/L (range, 2.4 to 496×109/L) and 78% (40% to 100%), respectively. Bioinformatic evaluation of the RNA-Seq data revealed 67 high-value novel fusions that were not detected by conventional karyotyping: 54 (80.6%) were intra- and 13 (19.4%) inter-chromosomal junctions. The number of novel translocations varied in different cytogenetic groups, with 22 novel fusions detected in those with NK (16 intra and 6 inter-chromosomal junctions), 37 CBF (32 intra and 5 inter-chromosomal junctions) and 8 in “other” (6 intra and 2 inter-chromosomal junctions). Thirteen novel fusions (19.4%) were found in at least 2 or more screened-patients: two (15.4%) inter- and 11 (84.6%) intra-chromosomal junctions. Median number of fusions identified per patient was 2 (range, 1 to 6). Novel fusions involving PDGFR-β gene were identified in two patients, each with a different translocation partner (G3BP1 and ETV6, which was an intra and inter-chromosomal fusions, respectively). Sequencing of the fusion transcript junctions verified the fusion junctions and demonstrated in frame fusions of G3BP1 and ETV6 to the kinase domain coding region of PDGFR-β, identical junction to that seen in cases of imatinib sensitive idiopathic hypereosinophilic syndrome (IHES). Frequency validation in 100 adult and 100 pediatric cases identified one additional patient with G3BP1-PDGFR-β. Cryptic NUP98/NSD1 was identified and verified in two patients with normal karyotype as well as NUP98/HOXD13 translocation in one patient. Frequency determination of NUP98/NSD1 demonstrated prevalence of 7.8% in patients with NK, and that of 13% in patients with FLT3/ITD. Patients who harbored both NUP98/NSD1 fusion and FLT3/ITD had a dismal remission induction rate (CR rate in FLT3/ITD with and without NUP98/NSD1 was 28% vs. 73%; p=0.002). Conclusion: Our data show the applicability of RNA-Seq as a tool to discover cryptic fusion transcripts in AML. These novel fusions may define new independent prognostic markers and potential therapeutic targets for patients with this highly treatment-resistant disease. Disclosures: No relevant conflicts of interest to declare.

Overall Hydroxymethylation Levels As an Independent Prognostic Marker in Intermediate-Cytogenetic Risk Acute Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1375-1375
Author(s):  
Marina Díaz-Beyá ◽  
Alfons Navarro ◽  
Rut Tejero ◽  
Marta Pratcorona ◽  
Tania Díaz ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Prognostic Markers ◽  
Response Rate ◽  
Wild Type ◽  
Mirna Signature ◽  
Worse Prognosis ◽  
Acute Myeloid

Abstract Abstract 1375 Introduction: Acute myeloid leukemia (AML) is a highly heterogeneous disease, with diverse genetic and epigenetic variables determining sensitivity to current standard therapy. A disruption of the normal DNA methylation pattern, which can result in altered gene and microRNA (miRNAs) expression, has been observed in different AML subtypes. Hydroxymethylation of 5-methylcytosine (5-mC) has recently been described as an intermediate key step in the process of DNA demethylation. Nonetheless, the correlation of DNA methylation and hydroxymethylation levels with clinical and biological characteristics and clinical outcome in AML is mostly unknown. Aim: To investigate the prognostic impact of overall methylation and hydroxymethylation levels in patients with intermediate-cytogenetic risk AML (IR-AML) and to identify miRNAs correlated with methylation and hydroxymethylation in these patients. Patients and Methods: We have analyzed 86 IR-AML patients (median age, 53 [range, 17–74]; 52% males) who received intensive therapy from 1994 to 2009 in a single institution. The level of overall methylation and hydroxymethylation in total DNA was estimated after determining the percentage of 5-mC and hydroxymethylcytosine (5-hmC), using anti-5-mC and anti-5-hmC monoclonal antibodies (MethylFlash Methylated or Hydroxymethylated DNA Quantification Kit, Epigentek). The expression of 670 mature miRNAs was analyzed using TaqMan Human MicroRNA Arrays (Applied Biosystems). The statistical analysis was performed with SPSS version 15.0.1 and R software version 2.9.0. MaxStat package of R was used to determine the optimal cutoffs. Results: The univariate analysis for overall methylation showed that patients with lower levels of methylation (cutoff < percentile 75) had shorter overall survival (OS) than those with higher 5-mC levels (5-year OS: 30±6% vs 52±11%; p=0.03) and a trend for shorter leukemia-free survival (LFS)(p=0.06). Overall methylation levels did not show any correlation with clinical features at diagnosis or with gene mutations, including DNMT3A. Concerning hydroxymethylation, patients with lower 5-hmC levels had a worse prognosis than those with higher 5-hmC levels, with a lower complete response rate (79% vs. 96%; p=0.04), shorter OS (5-yr OS: 21± 6% vs. 55± 6%; p=0.008), and shorter LFS (5-yr LFS: 24±8% vs. 52 ±10%; p=0.03). Interestingly, when analyzed as a continuous variable, 5-hmC levels retained their prognostic value as a marker of response rate (T-test, p=0.007), OS (Cox, p=0.015), and LFS (Cox, p=0.041). Moreover, 5-hmC levels were inversely correlated with FLT3-ITD (p=0.001) and the FLT3-ITD/FLT3wild-type ratio (Pearson correlation:-0.6; p=0.01). The multivariate analyses, including the main clinical and biological variables, identified older age, wild-type NPM1, FLT3-ITD, and lower 5-hmC levels (HR=3.072; 95% CI: 1.096–3.917; p=0.025) as independent prognostic markers of shorter OS and wild-type NPM1, FLT3-ITD, and lower 5-hmC levels (HR=2.002, 95% CI: 1.032–3.881, p=0.040) as independent prognostic markers of shorter LFS. Of note, lower 5-hmC levels retained their value as a marker of worse prognosis in the subgroup of IR-AML patients with unfavorable molecular markers (wild-type NPM1 and CEBPA and/or FLT3-ITD; p= 0.037). Finally, we have identified a 3-miRNA signature (miR-378*, p=0.02; miR-493, p=0.02; and miR-181, p=0.02) associated with global methylation levels, and a 12-miRNA signature associated with hydroxymethylation, including miR-183* (p=0.001), miR-125a-3p (p= 0.01), miR-586 (p=0.02), and miR-513–3p (p=0.02). Conclusions: Hydroxymethylation levels appear as an independent prognostic factor in IR-AML and maintain their prognostic value in the subset of patients with unfavorable molecular markers. Moreover, methylation and hydroxymethylation are associated with specific miRNA profiles. Further studies are warranted to confirm the clinical impact of these findings and to clarify the underlying molecular mechanisms. Disclosures: No relevant conflicts of interest to declare.

Prognostic value of renin gene expression in acute myeloid leukemia

2018 ◽  
Vol 43 (2) ◽  
pp. 69
Author(s):  
NevinM.Al Azhary ◽  
NahelaA Shalaby ◽  
DeenaS Eissa ◽  
NaglaaM Hassan ◽  
AmanyA Saleh
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Renin Gene ◽  
Acute Myeloid

Activating FLT3 Mutations Display a Wide Range Of Transforming Potential and a Characteristic Pathway Profile Associated With Prognosis In Acute Myeloid Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1312-1312
Author(s):  
Hanna Janke ◽  
Friederike Schneider ◽  
Daniela Schumacher ◽  
Tobias Herold ◽  
Hopfner Karl-Peter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Gene Expression Profile ◽  
Myeloid Leukemia ◽  
Normal Karyotype ◽  
Wide Range ◽  
Flt3 Mutations ◽  
Acute Myeloid

Abstract Background Internal tandem duplication (ITD) and pointmutations in the tyrosine kinase domain (TKD) of the receptor tyrosine kinase FLT3 occur in about 30% of patients with acute myeloid leukemia (AML). In contrast to the negative prognostic impact of FLT3-ITD in normal karyotype AML, FLT3 pointmutations occurring in the TKD and juxtamembrane (JM) region are less frequent and of unclear clinical impact. Although TKD mutations can induce resistance to tyrosine kinase inhibitors the individual transforming potential of FLT3 pointmutations has not been analysed in detail. In this study we have performed a comprehensive analysis of various FLT3 mutants in a comparative setting in vitro and analyzed gene expression profiles, and clinical outcome with respect to FLT3mutation status. Material and Methods We analyzed relapse and survival in 672 cytogenetically normal AML patients and the FLT3 status at diagnosis and relapse in 156 patients. In the murine Ba/F3 cell model we analyzed the transforming potential, subcellular localization, phosphorylation status and signaling properties of eight different FLT3 mutants. The investigated FLT3 mutations include three ITD of different length and insertion site, V592A in the JM region, common FLT3-TKD mutations D835V and D835Y as well as D839G and I867S in the second TKD. FLT3-D839G and -I867S were recently found in AML patients by our group during routine diagnostics but have not been functionally characterized before. The corresponding remission samples did not express these mutations. Further a gene expression profile analysis with respect to FLT3-ITD and -TKD mutation status and evaluation of differences in activation of predefined STAT5 target gene set was performed. Results In 672 normal karyotype AML patients FLT3-ITD, but not FLT3-TKD mutations were associated with an inferior relapse free and overall survival in multivariate analysis. In paired diagnosis-relapse samples FLT3-ITD showed higher stability (70%) compared to FLT3-TKD (30%). In vitro, FLT3-ITD induced a fully transformed phenotype in Ba/F3 cells, whereas FLT3 pointmutations showed a weaker but clearly transformed phenotype with gradual increase in proliferation and protection from apoptosis. The transforming capacity of the investigated mutants was associated with cell surface expression and tyrosine 591 phosphorylation of the FLT3 receptor. Western blot experiments revealed STAT5 activation only in FLT3-ITD transformed cells, further gene expression profile analyses displayed differences in predefined STAT5 target genes between FLT3-ITD and FLT3-TKD mutations. In contrast, FLT3-non-ITD mutants had an enhanced signal of AKT and MAPK activation. Further differences were found on mRNA level presenting deregulation of SOCS2, ENPP2, PRUNE2 and ART3 expression between FLT3-ITD, FLT3-TKD and FLT3-WT. Conclusion Although apparently divergent in response to treatment all functionally characterized mutants showed a clear gain-of-function phenotype with a wide range of transforming activity associated with clinical prognosis and signaling. Disclosures: No relevant conflicts of interest to declare.

Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia

Blood ◽  
2011 ◽  
Vol 118 (22) ◽  
pp. 5905-5913 ◽  
Author(s):  
Anna Staffas ◽  
Meena Kanduri ◽  
Randi Hovland ◽  
Richard Rosenquist ◽  
Hans Beier Ommen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Markers ◽  
Npm1 Mutation ◽  
Mutation Status ◽  
Expression Levels ◽  
Pediatric Aml ◽  
Gene Expression Levels ◽  
Acute Myeloid

Abstract Mutation status of FLT3, NPM1, CEBPA, and WT1 genes and gene expression levels of ERG, MN1, BAALC, FLT3, and WT1 have been identified as possible prognostic markers in acute myeloid leukemia (AML). We have performed a thorough prognostic evaluation of these genetic markers in patients with pediatric AML enrolled in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) 1993 or NOPHO 2004 protocols. Mutation status and expression levels were analyzed in 185 and 149 patients, respectively. Presence of FLT3-internal tandem duplication (ITD) was associated with significantly inferior event-free survival (EFS), whereas presence of an NPM1 mutation in the absence of FLT3-ITD correlated with significantly improved EFS. Furthermore, high levels of ERG and BAALC transcripts were associated with inferior EFS. No significant correlation with survival was seen for mutations in CEBPA and WT1 or with gene expression levels of MN1, FLT3, and WT1. In multivariate analysis, the presence of FLT3-ITD and high BAALC expression were identified as independent prognostic markers of inferior EFS. We conclude that analysis of the mutational status of FLT3 and NPM1 at diagnosis is important for prognostic stratification of patients with pediatric AML and that determination of the BAALC gene expression level can add valuable information.

scholarly journals Prognostic value of monosomal karyotype in comparison to complex aberrant karyotype in acute myeloid leukemia: a study on 824 cases with aberrant karyotype

Blood ◽  
2012 ◽  
Vol 119 (9) ◽  
pp. 2122-2125 ◽  
Author(s):  
Claudia Haferlach ◽  
Tamara Alpermann ◽  
Susanne Schnittger ◽  
Wolfgang Kern ◽  
Jörg Chromik ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Normal Karyotype ◽  
Complex Karyotype ◽  
Hazard Ratios ◽  
Number Of Patients ◽  
Prognostic Group ◽  
Monosomal Karyotype ◽  
Acute Myeloid

Abstract In acute myeloid leukemia (AML) the subset with complex karyotype (CK) is traditionally regarded as the worst prognostic group. However, ≥ 3, ≥ 4, or ≥ 5 abnormalities have been variably used for its definition. Recently, monosomal karyotype (MSK) was suggested to indicate an even inferior outcome. We tested which definition fits best to identify the most unfavorable subgroup. After excluding patients with t(15;17)/PML-RARA, t(8;21)/RUNX1-RUNX1T1, inv (16)/t(16;16)/CBFB-MYH11, and normal karyotype, 824 patients with AML with cytogenetic abnormalities were analyzed. Patients with MSK or CK defined as ≥ 3, ≥ 4, or ≥ 5 abnormalities showed an inferior overall survival compared with the respective remaining patients not fulfilling these criteria (for all, P < .001). Hazard ratios were 1.93, 1.68, 1.94, and 1.92. CK ≥ 4 as a single parameter identified the largest proportion of patients with very poor risk. However, combining CK ≥ 4 and MSK detected an even larger number of patients with very unfavorable outcome (261 of 824; 31.7%).

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