The molecular profile of adult T-cell acute lymphoblastic leukemia: mutations in RUNX1 and DNMT3A are associated with poor prognosis in T-ALL.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and heterogeneous disease. The diagnosis is predominantly based on immunophenotyping. In addition to known cytogenetic abnormalities molecular mutations were recently identified. Here, 90 adult T-ALL cases were investigated for mutations in NOTCH1, FBXW7, PHF6, CDKN2A, DNMT3A, FLT3, PTEN, and RUNX1 using 454 next-generation amplicon sequencing and melting curve analyses. These data were further complemented by FISH, chromosome banding, array CGH, and CDKN2B promoter methylation analyses. NOTCH1 was the most frequently mutated gene with a 71.1% frequency followed by FBXW7 (18.9%), PHF6 (39.5%), DNMT3A (17.8%), RUNX1 (15.5%), PTEN (10.0%), CDKN2A (4.4%), FLT3-ITD (2.2%), and FLT3-TKD (1.1%). In total, 84/90 (93.3%) cases harbored at least one mutation. Combining these data with CDKN2A/B deletions and CDKN2B methylation status, we detected minimum one aberration in 89/90 (98.9%) patients. Survival analyses revealed the subtype as defined by the immunophenotype as the strongest independent prognostic factor. When restricting the survival analysis to the early T-ALL subtype, a strong association of RUNX1 (P = 0.027) and DNMT3A (P = 0.005) mutations with shorter overall survival was observed. In conclusion, RUNX1 and DNMT3A are frequently mutated in T-ALL and are associated with poor prognosis in early T-ALL.

Discovering the truth in attempted suicide.

The findings of an international workshop on improving clinical interactions between mental health workers and suicidal patients are reported. Expert clinician-researchers identified common contemporary problems in interviews of suicide attempters. Various videotaped interviews of suicide attempters were critically discussed in relation to expert experience and the existing literature in this area. The working group agreed that current mental health practice often does not take into account the subjective experience of patients attempting suicide, and that contemporary clinical assessments of suicidal behavior are more clinician-centered than patient-centered. The group concluded that clinicians should strive for a shared understanding of the patient's suicidality; and that interviewers should be more aware of the suicidal patient's inner experience of mental pain and loss of self-respect. Collaborative and narrative approaches to the suicidal patient are more promising, enhancing the clinician's ability to empathize and help the patient begin to reestablish a sense of mastery, thereby strengthening the clinical alliance.

Therapist sensitivity towards emotional life-career issues and the working alliance with suicide attempters.

This study investigated the usefulness of an action theoretical model of suicide in interviewing suicide attempters. Eighteen interviews were video-recorded and transcribed. The patients' narratives were reconstructed and life-career issues relevant for the patient's suicidality formulated. Skin conductance response was used to determine narrative content associated with actualized emotions. Scores of the patients' ratings of helping alliance experienced in the interview were positively associated with the therapists' sensitivity towards emotionally relevant life-career issues. Furthermore, relationship satisfaction was related to a narrative interviewing style. We conclude that working alliance in clinical interviews with suicide attempters can be improved when the interviewer uses a patient-oriented approach aimed at understanding the patient's suicidality in the context of personal life-career, or identity issues.