Association of Next Generation Sequencing Based Genotypic Profiling with MICM Characteristics in NPM1 Mutated Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explain the clinicobiological heterogeneity of NPM1 mutated (NPM1mut) acute myeloid leukemia (AML) by analyzing the association between next-generation sequencing (NGS) profiles and MICM characteristics in patients with this AML subtype.@*METHODS@#Data of 238 NPM1mut patients with available NGS information on 112 genes related to blood disease was collected, and χ2 test and nonparametric test were used to analyze the distribution association between NGS-detecting mutations and conventional MICM parameters.@*RESULTS@#In entire NPM1mut cohort, totaling 240 NPM1 mutation events were identified, of whom 10 (10/240, 4.2%) were missense mutations, which did not involve any W288 or W290 locus and were found exclusively in NPM1mut/FLT3-ITD- group. All but one of these missense mutations (9/10, 90%) were accompanied by AML subtype-defining recurrent cytogenetic or molecular abnormalities, of which 7 cases were in the low risk and 2 in the high risk. NPM1mut occurred solely as an insertion/deletion (indel) type in the NPM1mut/FLT3-ITD+ group. The incidence of favorable plus unfavorable karyotypes in NPM1mut/FLT3-ITD- group was higher than in NPM1mut/FLT3-ITD+ group (6.4% vs. 0, P=0.031). The positive rates of CD34 and CD7 in NPM1mut/FLT3-ITD+ group were significantly higher than in NPM1mut/FLT3-ITD- group (CD34: 47.9% vs. 20.6%, P<0.001; CD7: 61.5% vs. 29.9%, P<0.001). Logistic analysis showed that FLT3-ITD independently predicted for CD34+ and CD7+ [odds ratio (OR)=5.29, 95%CI: 2.64-10.60, P<0.001; OR=3.47, 95%CI: 1.79-6.73, P<0.001; respectively]. Ras-pathway mutations independently predicted for HLA-DR+ (OR=4.05, 95%CI: 1.70-9.63, P=0.002), and KRAS mutation for MPO- (OR=0.18, 95%CI: 0.05-0.62, P=0.007). TET2/IDH1 mutations independently predicted for CD34- and CD7- (OR=0.26, 95%CI: 0.11-0.62, P=0.002; OR=0.30, 95%CI: 0.14-0.62, P=0.001; respectively), and MPO+ (OR=3.52, 95%CI: 1.48-8.38, P=0.004). DNMT3A-R882 independently predicted for CD7+ and HLA-DR+ (OR=3.59, 95%CI: 1.80-7.16, P<0.001; OR=13.41, 95%CI: 4.56-39.45, P<0.001; respectively), and DNMT3A mutation for MPO-(OR=0.35, 95%CI: 1.48-8.38, P=0.004).@*CONCLUSION@#Co-existing FLT3-ITD in NPM1mut AML independently predicts for CD34+ and CD7+, co-existing Ras-pathway mutation for HLA-DR+ and MPO-, co-existing TET2/IDH1 mutation for CD34-, CD7-, and MPO+, and co-existing DNMT3A mutation for HLA-DR+, CD7+, and MPO-, thereby providing a new mechanism explanation for the immunophenotypic heterogeneity of these AML patients.

The Mutated Gene Sequenced by NGS and the Correlation of Their Coexistent Mutual Exclusiveness in NPM1 Mutated Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinicobiological heterogeneity of NPM1 mutated (NPM1@*METHODS@#The NGS data based on 112 genes related to blood disease in 238 newly diagnosed patients with NPM1@*RESULTS@#Among all the patients, at least one co-mutation was detected out. The median number per case of the mutated genes, including NPM1@*CONCLUSION@#Prognoses of AML involving less common NPM1 missense mutations should be stated on a case by case basis. The mutational landscape and co-occurrence and mutual exclusivity correlations of NPM1

Clinical significance of automatic warning function of cardiac remote monitoring systems in preventing acute cardiac episodes

In addition to ambulatory Holter electrocardiographic recording and transtelephonic electrocardiographic monitoring [TTM], a cardiac remote monitoring system can provide an automatic warning function through the general packet radio service [GPRS] network, enabling earlier diagnosis, treatment and improved outcome of cardiac diseases. The purpose of this study was to estimate its clinical significance in preventing acute cardiac episodes. Using 2 leads [V1 and V5 leads] and the automatic warning mode, 7160 patients were tested with a cardiac remote monitoring system from October 2004 to September 2007. If malignant arrhythmias or obvious ST-T changes appeared in the electrocardiogram records was automatically transferred to the monitoring center, the patient and his family members were informed, and the corresponding precautionary or therapeutic measures were implemented immediately. In our study, 274 cases of malignant arrhythmia, including sinus standstill and ventricular tachycardia, and 43 cases of obvious ST-segment elevation were detected and treated. Because of early detection, there was no death or deformity. A cardiac remote monitoring system providing an automatic warning function can play an important role in preventing acute cardiac episodes

Impact of diabetes on dynamics of serum myocardium biomarkers, infarct size, and in hospital outcomes in patients with a first acute myocardial infarction

Diabetic patients with acute myocardial infarction [AMI] have poor prognosis. The aim of this study was to compare the influence of diabetes on prognosis after AMI by serial changes of serum myocardium biomarkers and infarct size. CK-MBmass and CK-MBact were measured by the microparticle enzyme immunoassay and immunoinhibition assay respectively. The size of the myocardial infarction area was calculated on the basis of serial changes. In diabetic AMI patients [n=72], the peak values of CK-MBmass and CK-MBact appeared at 23.1 h and 24.2 h, and maintained at peak level for 16.6 h and 17.3 h before returned to normal by 62.3 h and 69.2 h respectively. In contrary, the peak values of these enzymes in non-diabetic AMI surfers [n=154] returned to normal by 58.4 h and 63.2 h respectively [both P<0.01]. Patients with diabetes also had larger infarct size as calculated by the serial serum measurements of CK-MBmass [47.3 +/- 10.5 vs 41.6 +/- 10.7, P<0.01] and CK-MBact [52.4 +/- 12.8 vs 46.9 +/- 13.4, P<0.01], accompanying with higher occurrences of arrhythmias [40.3% vs 29.9%, P<0.01], cardiac dysfunction [34.7% vs 24.0%, P<0.01], and mortality [11.1% vs 7.1%, P<0.01]. Diabetic patients with AMI are associated with increased release of serum myocardium biomarkers, larger infarct size, and higher incidence of in-hospital complications and mortality. These associations could explain the poor prognosis in diabetic patients with AMI