Simultaneous detection of ABL1 mutation and IKZF1 deletion in Philadelphia chromosome-positive acute lymphoblastic leukemia using a customized target enrichment system panel.

INTRODUCTION: Recent clinical outcomes of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) vastly improved owing to tyrosine kinase inhibitor (TKI). However, the genetic status would be different in each case with ABL1 gene mutation or copy number variants (CNVs) such as IKZF1 deletion. In particular, the TKI resistant clone with ABL1 kinase mutation remains problematic. The comprehensive assessment of genetic status including mutation, insertion and deletion (indel) and CNVs is necessary. METHODS: We evaluated a next-generation sequencing (NGS)-based customized HaloPlex target enrichment system panel to simultaneously detect coding mutations, indel and CNVs. We analysed approximately 160 known genes associated with hematological disorders in 5 pediatric Ph+ALL patients. RESULTS: Mono-allelic IKZF1 deletions were found in 4 patients at diagnosis. Furthermore, the mono-allelic deletions were found in exons of RB1, EBF1, PAX5 and ETV6 genes. Bi-allelic deletions were detected in CDKN2A and CDKN2B genes in 1 patient. ABL1 mutation was also detected in 1 patient at relapse. These results were almost comparable with the results of the multiplex ligation-dependent probe amplification (MLPA) method or Sanger sequence. CONCLUSION: Next-generation sequencing-based custom HaloPlex target enrichment system panel allows us to detect the coding mutations, indel, and CNVs in pediatric Ph+ALL simultaneously, and its results seem comparable with those of other methods.

Cardiac tumor biopsy under the guidance of intracardiac echocardiography.

Transthoracic echocardiography or transesophageal echocardiography is sometimes useful in intracardiac tumor biopsy. Intracardiac echocardiography was used as an alternative to either of these for performing a biopsy of a right cardiac tumor in a 79-year-old woman. The procedure was well tolerated and no complications occurred. Histopathological findings and immunohistological staining were compatible with the diagnosis of neurogenic sarcoma.

Dependency on atrial electrophysiological properties of appearance of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome: evidence from atrial vulnerability before and after radiofrequency catheter ablation and surgical cryoablation.

The pathogenesis of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome and the effects of elimination of accessory pathways on the appearance of atrial fibrillation are still controversial. Fifty-four patients with Wolff-Parkinson-White syndrome were classified into three groups: a No AF group (n = 24), patients without paroxysmal atrial fibrillation; an RF-AF Group (n = 12), patients with paroxysmal atrial fibrillation whose accessory pathways were eliminated using radiofrequency catheter ablation; and a Cryo-AF Group (n = 18), patients with paroxysmal atrial fibrillation whose accessory pathways were eliminated with surgical cryoablation. The electrophysiological characteristics of each group were evaluated prior to and following the elimination of their accessory pathways. As indices of atrial vulnerability, the presence of fragmented atrial activity and repetitive atrial firing zones were assessed. Inducibility of atrial fibrillation was significantly reduced following ablation of accessory pathways in the Cryo-AF group (83.3%-5.6%, P < 0.0001), while it was unchanged in the RF-AF group (83.3%-75%). In preablation studies, the effective refractory periods of the atrium in the RF-AF group and the Cryo-AF group were significantly shorter compared with the No AF group (204 +/- 18 ms, 197 +/- 16 ms vs 246 +/- 44 ms, respectively, P < 0.0001). Following ablation, the effective refractory period for patients in the Cryo-AF group was significantly prolonged compared with before ablation (197 +/- 16 ms to 232 +/- 24 ms, P < 0.0001). As a result of this prolongation of the effective refractory period of the atrium, the fragmented atrial activity and repetitive atrial response zones narrowed following ablation in the Cryo-AF group, but not in the RF-AF group. Therefore, the pathogenesis of atrial fibrillation in patients with Wolff-Parkinson-White syndrome may depend on the refractory period of the atrium rather than on the presence of accessory pathways.

The role of the accessory pathway in the onset of atrial fibrillation in Wolff-Parkinson-White syndrome--electrophysiological examination before and after surgical ablation.

To determine the role of the accessory pathway in the pathogenesis of atrial fibrillation, we compared electrophysiological findings in 17 patients (44.7 +/- 10.2 years) with a history of atrial fibrillation before and after surgical ablation of the accessory pathway. The PA interval was shortened, and the atrial refractory periods and the potential minimal wavelength of an atrial impulse (FRPA/PA) were significantly increased, after surgery. Fragmented atrial activity (an increase of 150% or more in the duration of the high right atrial electrogram) was observed in 80% of the patients before surgery and in 25% after surgery. Its zone was significantly decreased after surgery. Repetitive atrial firing was defined as the occurrence of 3 or more successive atrial electrograms induced by a premature stimulation. This was observed in 60% of the patients before surgery, but in none after surgery. Atrial fibrillation was induced in 16 patients during the preoperative study, but in only 1 patient postoperatively. In conclusion, these results suggest that accessory pathways affect atrial vulnerability and play an important role in the onset of atrial fibrillation in WPW syndrome.