scholarly journals Coexistence and Prognostic Significance of EVI1 Expression and Driver Mutations in KMT2A-Rearranged Acute Myeloid Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1409-1409 ◽  
Author(s):  
Hidemasa Matsuo ◽  
Kenichi Yoshida ◽  
Kana Nakatani ◽  
Yasuhiko Kamikubo ◽  
Daisuke Tomizawa ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Prognostic Significance ◽  
Adult Patients ◽  
Driver Mutations ◽  
Significant Difference ◽  
Equity Ownership ◽  
Acute Myeloid

Background: KMT2A(MLL)-rearrangements are among the most frequent chromosomal abnormalities in acute myeloid leukemia (AML) and high EVI1 expression is known as an adverse prognostic factor in this subgroup. A recent study showed driver mutations are associated with poor prognosis in pediatric KMT2A-rearranged AML, however, the relationship between EVI1 expression and driver mutations is unclear. In this study, we examined coexistence and prognostic significance of these genetic abnormalities in pediatric and adult KMT2A-rearranged AML. Patients and Methods: Forty-four pediatric KMT2A-rearranged AML samples collected in the AML-05 study, conducted by the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG), were analyzed for 338 genes by targeted sequencing. In addition, 85 adult KMT2A-rearranged AML samples in MLL Munich Leukemia Laboratory were analyzed for 16 genes (ASXL1, BRAF, CBL, CEBPA, FLT3-ITD, FLT3-TKD, IDH1, IDH2, KIT, KRAS, NPM1, NRAS, PTPN11, RUNX1, TP53 and WT1) by amplicon deep-sequencing, direct Sanger sequencing, or melting curve analysis. In both studies, EVI1 expression was measured using quantitative RT-PCR. Results and Discussion: In pediatric KMT2A-rearranged AML (n=44), among 28 patients with low EVI1 expression, 13 patients (EVI1-WT, 46.4%) had no driver mutations and 15 patients (EVI1-MT, 53.6%) had one or more driver mutations. Among 16 patients with high EVI1 expression, 2 patients (EVI1+WT, 12.5%) had no driver mutations and 14 patients (EVI1+MT, 87.5%) had one or more driver mutations. Mutations in activated signaling pathway genes (FLT3, NRAS, KRAS, PTPN11, CBL, and BRAF) were detected in most patients with EVI1-MT (12/15, 80.0%) and EVI1+MT (13/14, 93.3%). The frequency of mutations in epigenetic regulator genes (SETD2, ASXL1, ASXL2, BCOR, KDM6A, and CREBBP) was significantly higher in EVI1-MT patients (7/15, 46.7%), compared with EVI1+MT patients (1/14, 7.1%) (P=0.04). By contrast, the frequency of mutations in cohesion complex genes (STAG2 and SMC3) was significantly lower in patients with EVI1-MT patients (0/15, 0.0%), compared with EVI1+MT patients (4/14, 28.6%) (P=0.04). The frequency of mutations in transcription factor genes (WT1, MECOM, SPI1, GATA2, and RUNX1) was also lower in EVI1-MT patients (2/15, 13.3%), compared with EVI1+MT patients (5/14, 35.7%) (P=0.21). In adult patients, the frequency of ASXL1 mutations was higher in EVI1-MT patients (3/18, 18.8%), compared with EVI1+MT patients (1/29, 3.4%) (P=0.15) and those of WT1 and RUNX1 mutations were lower in EVI1-MT patients (0/18, 0.0%), compared with EVI1+MT patients (4/29, 13.8%) (P=0.28), which were compatible with the tendency in pediatric KMT2A-rearranged AML. Next, we examined the prognostic significance of EVI1 expression and driver mutations. Compared with EVI1-WT patients, EVI1-MT patients had lower event-free survival (EFS) (3-years EFS: 84.6% vs. 65.2%, P=0.24). EFS of EVI1+MT patients (3-years EFS: 30.8%) was significantly lower than that of EVI1-WT patients (P=0.001) and EVI1-MT patients (P=0.04). EFS of EVI1+WT patients (3-years EFS: 0.0%) was also lower than that of EVI1-WT patients (P=0.003) and EVI1-MT patients (P=0.09). There was no significant difference in EFS between EVI1+WT and EVI1+MT patients (P=0.88). The results of overall survival (OS) were similar except for EVI1+WT patients (n=2) (3-years OS: EVI1-WT 92.3%, EVI1-MT 70.6%, EVI1+WT 100.0%, EVI1+MT 46.6%). Multivariate analysis including EVI1 expression, driver mutations, age, white blood cell count, and KMT2A-MLLT4 fusion showed EVI1+ is an independent prognostic factor for EFS (hazard ratio (HR): 3.02, 95% confidence interval (CI): 1.08-9.48, P=0.04). There was no prognostic significance in driver mutations (HR:1.24, 95%CI: 0.39-4.74, P=0.73). As a whole, adult patients' survival data were lower, however, the tendency was similar to that of pediatric data (3-years EFS: EVI1-WT 41.7%, EVI1-MT 24.5%, EVI1+WT 9.1%, EVI1+MT 13.5%; 3-years OS: EVI1-WT 55.6%, EVI1-MT 30.7%, EVI1+WT 18.2%, EVI1+MT 36.2%). These data showed that there is an association between EVI1 expression and the pathway of driver mutations, suggesting these abnormalities may have some cooperative mechanisms in leukemogenesis. Compared with driver mutations, high EVI1 expression may have a stronger impact on poor prognosis in KMT2A-rearranged AML, however, the results should be confirmed in the larger cohort. Disclosures Ogawa: RegCell Corporation: Equity Ownership; Kan Research Laboratory, Inc.: Consultancy; ChordiaTherapeutics, Inc.: Consultancy, Equity Ownership; Dainippon-Sumitomo Pharmaceutical, Inc.: Research Funding; Asahi Genomics: Equity Ownership; Qiagen Corporation: Patents & Royalties. Meggendorfer:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

Expression of c-mpl mRNA, the receptor for thrombopoietin, in acute myeloid leukemia blasts identifies a group of patients with poor response to intensive chemotherapy.

1997 ◽  
Vol 15 (6) ◽  
pp. 2262-2268 ◽  
Author(s):  
M Wetzler ◽  
M R Baer ◽  
S H Bernstein ◽  
L Blumenson ◽  
C Stewart ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Prognostic Significance ◽  
Poor Response ◽  
Significant Difference ◽  
De Novo Aml ◽  
Cd34 Expression ◽  
Acute Myeloid

PURPOSE c-mpl, the human homolog of v-mpl, is the receptor for thrombopoietin. Given that c-mpl expression carries an adverse prognosis in myelodysplastic syndrome and given the prognostic significance of expression of other growth factor receptors in other diseases, we attempted to determine whether c-mp/mRNA expression is a prognostic factor in acute myeloid leukemia (AML). PATIENTS AND METHODS We analyzed bone marrow samples from 45 newly diagnosed AML patients by reverse-transcription polymerase chain reaction. RESULTS Samples from 27 patients (60%) expressed c-mpl mRNA (c-mpl+); their clinical and laboratory features were compared with those of the 18 patients without detectable levels of c-mpl(c-mpl-). No significant differences in age, sex, leukocyte count, French-American-British subtype, or karyotype group were found. c-mpl+ patients more commonly had secondary AML (41% v 11%; P = .046) and more commonly expressed CD34 (67% v 12%; P = .0004). There was no significant difference in complete remission (CR) rate. However, c-mpl+ patients had shorter CR durations (P = .008; median, 6.0 v > 17.0 months). This was true when only de novo AML patients were considered and when controlling for age, cytogenetics, or CD34 expression. There was a trend toward shorter survival in c-mpl+ patients (P = .058; median, 7.8 v 9.0 months). CONCLUSION These data suggest that c-mpl expression is an adverse prognostic factor for treatment outcome in adult AML that must be considered in the analysis of clinical studies using thrombopoietin in AML.

scholarly journals The Prognostic Significance of IRF8 Transcripts in Adult Patients with Acute Myeloid Leukemia

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e70812 ◽  
Author(s):  
Era L. Pogosova-Agadjanyan ◽  
Kenneth J. Kopecky ◽  
Fabiana Ostronoff ◽  
Frederick R. Appelbaum ◽  
John Godwin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Adult Patients ◽  
Acute Myeloid

scholarly journals High CXCR2 expression predicts poor prognosis in adult patients with acute myeloid leukemia

2020 ◽  
Vol 11 ◽  
pp. 204062072095858
Author(s):  
Wei Tang ◽  
Zunyan Li ◽  
Xian Li ◽  
Zhonghua Huo
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Mononuclear Cells ◽  
Cox Proportional Hazards ◽  
Adult Patients ◽  
The Cancer Genome Atlas ◽  
Clinical Parameters ◽  
Cxcr2 Expression ◽  
Acute Myeloid

Aims: This study aimed to assess the associations between clinical parameters, long-term outcomes, and expression of chemokine receptor CXCR2 in patients with acute myeloid leukemia (AML). Methods: From May 2013 to May 2017, 83 adult patients newly diagnosed with AML in the Affiliated Hospital of BeiHua University and Jilin Chemical Hospital, were enrolled in this study. The expression of CXCR2 in bone marrow mononuclear cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Clinical information and RNA-sequencing datasets of The Cancer Genome Atlas (TCGA) ( n = 136) were obtained. The associations between clinical parameters, prognosis, and CXCR2 expression were analyzed. Results: From both cohorts, patients with AML with M4 and M5 subtypes showed higher CXCR2 expression levels than those with other French-American-British (FAB) subtypes. Patients with extramedullary leukemia infiltration had higher CXCR2 levels than those without. In our cohort, patients with high CXCR2 levels (⩾2.099) had lower relapse-free survival (RFS) ( p < 0.000001) and overall survival (OS) ( p = 0.000107) than those with low levels (<2.099). High CXCR2 levels (⩾2.082) also indicated a poor OS in the TCGA cohort but only in patients younger than 65 years (5-year OS: 7.7% versus 29.9% in those with CXCR2 levels < 2.082). High CXCR2 levels independently predicted poor prognosis in AML patients, as determined by Cox proportional hazards models. Conclusion: Our results suggest that high CXCR2 expression associates with the monocytic lineage of AML and is an independent risk factor for poor patient prognosis.

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.

scholarly journals High Expression of PXN Predicts a Poor Prognosis in Acute myeloid leukemia

2021 ◽  
Author(s):  
xinwen zhang ◽  
Hao Xiong ◽  
Jialin Duan ◽  
Xiaomin Chen ◽  
Yang Liu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Receive Treatment ◽  
To Receive ◽  
Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) is one of the common malignant diseases of hematopoietic system. Paxillin ( PXN ) is an important part of focal adhesions (FAs), which is related to the poor prognosis of many kinds of malignant tumors. However, no research has focused on the expression of PXN in AML. We aimed to investigate the expression of PXN in AML and its prognostic significance. Methods: Using GEPIA and UALCAN database to analyze the expression of PXN in AML patients and its prognostic significance. Bone marrow samples of newly diagnosed AML patients were collected to extract RNA, and qRT-PCR was used to detect the expression of PXN . The prognosis was followed up. Chi-square test was used to analyze the relationship between PXN expression and clinical laboratory characteristics. Kaplan-Meier analysis was used to draw survival curve, and Cox regression analysis was used to analyze the independent factors affecting the prognosis of patients with AML. The co-expression genes of PXN were analyzed by LinkedOmics to explore its biological significance in AML. Results: Kaplan-Meier analysis showed that the overall survival time of AML patients was related to whether to receive treatment and PXN expression(P<0.05). COX regression analysis showed that whether to receive treatment (HR=0.227，95%CI=0.075-0.689， P =0.009) and high expression of PXN (HR=4.484，95%CI=1.449-13.889， P =0.009) were independent poor prognostic factors in patients with AML. Conclusion: PXN is highly expressed in AML patient, and high PXN expression is an indicator of poor prognosis in AML patient.

scholarly journals The Expression of I-Mfa in Adult Patients with De Novo Acute Myeloid Leukemia and Its Clinical Significance

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5316-5316
Author(s):  
Bing Xu ◽  
Huijuan Dong ◽  
Feili Chen ◽  
Yong Zhou ◽  
Jiabao Liang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Clinical Significance ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Adult Patients ◽  
Expression Level ◽  
Significant Difference ◽  
Median Expression ◽  
Acute Myeloid

Abstract Background: I-mfa has been identified as an inhibitor of MyoD and other related myogenic basic helix-loop-helix proteins. I-mfa contains a cysteine-rich C-terminal domain, and has been reported to function as transcriptional regulator of different pathways including Wnt signaling, c-jun N-terminal kinase signaling, and the regulatory properties of I-mfa depend on the C-terminal domain. Furthermore, recent studies have found that the I-mfa domain may have a close correlation with the development of myeloid neoplasms, however the role of I-mfa in adult patients with de novo acute myeloid leukemia still remain unclear. Aims: The aim of this study was to determine I-mfa expression in adult patients with de novo acute myeloid leukemia and its clinical significance. Methods: BM samples form 110 adult patients with de novo AML were analyzed. Of the 110 AML patients, 66 were males and 44 were females, with a mean age of 32 years( range from 12 to 77 years). Among them, 1 out of 110 patients was M1, 49 were M2, 14 were M4, 28 were M5, 1was M6 and 17 were acute unclassified leukemia. All patients received 1 to 2 cycles of induction of standard-dose cytarabine continuous infusion×7 days with idarubicin or daunorubicin×3days, fellowed by consolidation therapy with HiDAC and then stem cell transplantation according to patient’s condition. Real-time reverse transcription-polymerase chain reaction(RT-PCR) was used to detect the expression of I-mfa gene in 110 de novo adult AML patients, and the patients were divided into high and low I-mfa expression groups accordint to the median expression of I-mfa mRNA. Comparisons were performed using Mann-Whitney U test, Chi-square test and Kaplan-Meier method. Results:Distribution of I-mfa gene expression in different FAB subtypes was with no significant differences (P=0.169). The median age of AML pateints in low and high I-mfa gene epxression groups were 35 and 40 years old(P=0.162), and the median expression of I-mfa in 44 female patients and 66 male patients was 0.018 and 0.013 separately(P=0.728). What’s more, there was no significant difference of WBC, Hb level, PLT, bone marrow blast counts between the two groups (P＞0.05), and the I-mfa expression level was also not correlated with chromosome risk stratification and the expression of CD34 (P＞0.05). High I-mfa expression group had a lower complete remission rate than that in the low expression group (81.8% vs 63.6%, P=0.032), However, the overall survival rate was with no significant difference in the low and hign I-mfa gene expression groups(76.4% vs 76.4%, P=0.471). Conclusions: Our results showed high I-mfa expression correlates with a poor treatment response, the OS rate was with no significant difference in the two groups. There is somewhat correlation between the expression level of I-mfa gene and prognosis and the expression of I-mfa may be a prognostic factor for adult patients with de novo acute myeloid leukemia. Disclosures No relevant conflicts of interest to declare.

Clonal Heterogeneity As Detected by Metaphase Karyotyping Is an Indicator of Poor Prognosis in Acute Myeloid Leukemia

2013 ◽  
Vol 31 (31) ◽  
pp. 3898-3905 ◽  
Author(s):  
Tilmann Bochtler ◽  
Friedrich Stölzel ◽  
Christoph E. Heilig ◽  
Christina Kunz ◽  
Brigitte Mohr ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Clonal Evolution ◽  
Prognostic Significance ◽  
Genomic Diversity ◽  
Prognostic Information ◽  
Clonal Heterogeneity ◽  
Landmark Analyses ◽  
Acute Myeloid

Purpose In acute myeloid leukemia (AML), studies based on whole-genome sequencing have shown genomic diversity within leukemic clones. The aim of this study was to address clonal heterogeneity in AML based on metaphase cytogenetics. Patients and Methods This analysis included all patients enrolled onto two consecutive, prospective, randomized multicenter trials of the Study Alliance Leukemia. Patients were newly diagnosed with non-M3 AML and were fit for intensive chemotherapy. Results Cytogenetic subclones were detected in 418 (15.8%) of 2,639 patients from the whole study population and in 418 (32.8%) of 1,274 patients with aberrant karyotypes. Among those, 252 karyotypes (60.3%) displayed a defined number of distinct subclones, and 166 (39.7%) were classified as composite karyotypes. Subclone formation was particularly frequent in the cytogenetically adverse group, with subclone formation in 69.0%, 67.1%, and 64.8% of patients with complex aberrant, monosomal, and abnl(17p) karyotypes (P < .001 each). Two-subclone patterns typically followed a mother-daughter evolution, whereas for ≥ three subclones, a branched pattern prevailed. In non–core binding factor AML, subclone formation was associated with inferior event-free and overall survival and was confirmed as an independent predictor of poor prognosis in multivariate analysis. Subgroup analysis showed that subclone formation adds prognostic information particularly in the cytogenetic adverse-risk group. Allogeneic stem-cell transplantation improved the prognosis of patients with subclone karyotypes as shown in landmark analyses. Conclusion Cytogenetic subclones are frequent in AML and permit tracing of clonal evolution and architecture. They bear prognostic significance with clonal heterogeneity as an independent adverse prognostic marker in cytogenetically adverse-risk AML.

The prognostic significance of IDH1 mutations in younger adult patients with acute myeloid leukemia is dependent on FLT3/ITD status

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2779-2782 ◽  
Author(s):  
Claire L. Green ◽  
Catherine M. Evans ◽  
Robert K. Hills ◽  
Alan K. Burnett ◽  
David C. Linch ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Idh1 Mutation ◽  
Adult Patients ◽  
Npm1 Mutation ◽  
Mutation Status ◽  
The United Kingdom ◽  
Dehydrogenase Gene ◽  
Acute Myeloid

Abstract Mutations in the isocitrate dehydrogenase gene (IDH1) were recently described in patients with acute myeloid leukemia (AML). To investigate their prognostic significance we determined IDH1 status in 1333 young adult patients, excluding acute promyelocytic leukemia, treated in the United Kingdom MRC AML10 and 12 trials. A mutation was detected in 107 patients (8%). Most IDH1+ patients (91%) had intermediate-risk cytogenetics. Mutations correlated significantly with an NPM1 mutation (P < .0001) but not a FLT3/ITD (P = .9). No difference in outcome between IDH1+ and IDH1− patients was found in univariate or multivariate analysis, or if the results were stratified by NPM1 mutation status. However, when stratified by FLT3/ITD status, an IDH1 mutation was an independent adverse factor for relapse in FLT3/ITD− patients (P = .008) and a favorable factor in FLT3/ITD+ patients (P = .02). These results suggest that metabolic changes induced by an IDH1 mutation may influence chemoresistance in a manner that is context-dependent.

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