KIT-D816V-independent oncogenic signaling in neoplastic cells in systemic mastocytosis: role of Lyn and Btk activation and disruption by dasatinib and bosutinib

Systemic mastocytosis (SM) either presents as a malignant neoplasm with short survival or as an indolent disease with normal life expectancy. In both instances, neoplastic mast cells (MCs) harbor D816V-mutated KIT, suggesting that additional oncogenic mechanisms are involved in malignant transformation. We here describe that Lyn and Btk are phosphorylated in a KIT-independent manner in neoplastic MCs in advanced SM and in the MC leukemia cell line HMC-1. Lyn and Btk activation was not only detected in KIT D816V-positive HMC-1.2 cells, but also in the KIT D816V-negative HMC-1.1 subclone. Moreover, KIT D816V did not induce Lyn/Btk activation in Ba/F3 cells, and deactivation of KIT D816V by midostaurin did not alter Lyn/Btk activation. siRNAs against Btk and Lyn were found to block survival in neoplastic MCs and to cooperate with midostaurin in producing growth inhibition. Growth inhibitory effects were also obtained with 2 targeted drugs, dasatinib which blocks KIT, Lyn, and Btk activation in MCs, and bosutinib, a drug that deactivates Lyn and Btk without blocking KIT activity. Together, KIT-independent signaling via Lyn/Btk contributes to growth of neoplastic MCs in advanced SM. Dasatinib and bosutinib disrupt Lyn/Btk-driven oncogenic signaling in neoplastic MC, which may have clinical implications and explain synergistic drug interactions.     

Nursing emotion work and interprofessional collaboration in general internal medicine wards: a qualitative study

Title. Nursing emotion work and interprofessional collaboration in general internal medicine wards: a qualitative study Aim. This paper is a report of a study to examine nursing emotion work and interprofessional collaboration in order to understand and improve collaborative nursing practice. Background. Nursing standards identify collaborative practice as necessary for quality patient care yet many nurses are often reluctant to participate in interprofessional teams. Strategies intended to improve participation often fail which suggests that the factors underpinning nurses’ disinclination towards interprofessional collaboration have yet to be understood. The concept of emotion work has not been applied to nursing interprofessionalism, and holds the potential to improve collaborative practice. Nursing emotion work is defined as the management of the emotions of self and others in order to improve patient care. Methods. Qualitative data were collected in 2006 using non‐participant observation, shadowing and semi‐structured interviews with nursing, medical and allied professionals in the general internal medicine wards of three hospitals in urban Canada. Findings. Nurses’ collaborations with other professionals are influenced by emotion work considerations. The establishment and maintenance of a nursing esprit de corps, corridor conflicts with physicians, and the failure of the interdisciplinary team to acknowledge the importance of nursing’s core caring values are important factors underpinning nurses’ interprofessional disengagement. Conclusion. Longstanding emotion work issues must be addressed before nurses will engage collaboratively. We suggest improving nursing collaboration through the refining of holistic nursing information, and reflections on practice by all interprofessional team members.     

Emotion identification in girls at high risk for depression

Background: Children of depressed mothers are themselves at elevated risk for developing a depressive disorder. We have little understanding, however, of the specific factors that contribute to this increased risk. This study investigated whether never‐disordered daughters whose mothers have experienced recurrent episodes of depression during their daughters’ lifetime differ from never‐disordered daughters of never‐disordered mothers in their processing of facial expressions of emotion. Method: Following a negative mood induction, daughters completed an emotion identification task in which they watched faces slowly change from a neutral to a full‐intensity happy, sad, or angry expression. We assessed both the intensity that was required to accurately identify the emotion being expressed and errors in emotion identification. Results: Daughters of depressed mothers required greater intensity than did daughters of control mothers to accurately identify sad facial expressions; they also made significantly more errors identifying angry expressions. Conclusion: Cognitive biases may increase vulnerability for the onset of disorders and should be considered in early intervention and prevention efforts.     

Available and emerging therapies for bona fide advanced systemic mastocytosis and primary eosinophilic neoplasms

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Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes

Eosinophilia and eosinophil activation are recurrent features in various reactive states and certain hematologic malignancies. In patients with hypereosinophilia (HE), HE-induced organ damage is often encountered and may lead to the diagnosis of a hypereosinophilic syndrome (HES). A number of known mechanisms and etiologies contribute to the development of HE and HES. Based on these etiologies and the origin of eosinophils, HE and HES are divided into primary forms where eosinophils are clonal cells, reactive forms where an underlying reactive or neoplastic condition is detected and eosinophils are considered to be “non-clonal” cells, and idiopathic HE and HES in which neither a clonal nor a reactive underlying pathology is detected. Since 2012, this classification and the related criteria have been widely accepted and regarded as standard. However, during the past few years, new developments in the field and an increasing number of markers and targets have created a need to update these criteria and the classification of HE and HES. To address this challenge, a Working Conference on eosinophil disorders was organized in 2021. In this conference, a panel of experts representing the relevant fields, including allergy, dermatology, hematology, immunology, laboratory medicine, and pathology, met and discussed new markers and concepts as well as refinements in definitions, criteria and classifications of HE and HES. The outcomes of this conference are presented in this article and should assist in the diagnosis and management of patients with HE and HES in daily practice and in the preparation and conduct of clinical trials.