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In allogeneic hematopoietic stem cell transplantation, which is the major curative therapy for hematological malignancies, T cells play a key role in the development of graft-versus-host disease (GvHD). NOTCH pathway is a conserved signal transduction system that regulates T cell development and differentiation. The present review analyses the role of the NOTCH signaling as a new regulator of acute GvHD. NOTCH signaling could also represent a new therapeutic target for GvHD. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) is an incurable B-cell neoplasm characterized by highly variable clinical outcomes. In recent years, genomic and molecular studies revealed a remarkable heterogeneity in CLL, which mirrored the clinical diversity of this disease. These studies profoundly enhanced our understanding of leukemia cell biology and led to the identification of new biomarkers with potential prognostic and therapeutic significance. Accumulating evidence indicates a key role of deregulated NOTCH1 signaling and NOTCH1 mutations in CLL. This review highlights recent discoveries that improve our understanding of the pathophysiological NOTCH1 signaling in CLL and the clinical impact of NOTCH1 mutations in retrospective and prospective trials. In addition, we discuss the rationale for a therapeutic strategy aiming at inhibiting NOTCH1 signaling in CLL, along with an overview on the currently available NOTCH1-directed approaches. [ABSTRACT FROM AUTHOR]

The article presents a case study of a novel NOTCH1 mutation of the proline, glutamic acid, serine and threonine (PEST) domain in a 65-year-old male with chronic lymphocytic leukemia (CLL). He received three cycles of hemoimmunotherapy with rituximab and fludarabine due to disease progression. He died after one month due to worsening of his conditions associated with persistent thrombocytopenia, anemia and lymphocytosis.

The article offers information on the advancement in the process of diagnosis, prognosis, and treatment of B-cell chronic lymphocytic leukaemia (B-CLL). It mentions that high expression of zeta-chain-associated protein kinase 70 (ZAP-70) and unmutated immunoglobulin heavy variable (IGHV) genes are considered poor factors for prognosis. It informs that NOTCH1 and PEST mutations are considered as marker of poor prognosis in a minority of B-CLL patients.