Mantle Cell Lymphoma Under the Scope of Personalized Medicine: Perspective and Directions.

Mantle cell lymphoma (MCL) is a rare, incurable non-Hodgkin's lymphoma characterized by naive B cells infiltrating the lymphoid follicle's mantle zone. A key feature of MCL is the cytogenetic abnormality t(11;14) (q13:q14), found in 95% of cases, leading to Cyclin D1 overexpression resulting in uncontrolled cell cycle progression and genetic instability. Occasionally, Cyclin D2 or D3 overexpression can substitute for Cyclin D1, causing similar effects. The transcription factor SOX11 is a hallmark of classical Cyclin D1-positive MCL and also in cases without the typical t(11;14) abnormality, making it an important diagnostic marker. MCL's development necessitates secondary genetic changes, including mutations in the ATM, TP53, and NOTCH1 genes, with the TP53 mutation being the only genetic biomarker with established clinical prognostic value. The Mantle Cell Lymphoma International Prognostic Index (MIPI) score, which considers age, performance status, serum LDH levels, and leukocyte count, stratifies patients into risk groups. Histologic variants of MCL, such as classic, blastoid, and pleomorphic, offer additional prognostic information. Recent research highlights new mutations potentially tied to specific populations among MCL patients, suggesting the benefit of personalized management for better predicting outcomes like progression-free survival. This approach could lead to more effective, risk-adapted treatment strategies. However, challenges remain in patient stratification and in developing new therapeutic targets for MCL. This review synthesizes current knowledge on genetic mutations in MCL and their impact on prognosis. It aims to explore the prognostic value of genetic markers related to population traits, emphasizing the importance of tailored molecular medicine in MCL.

Gradual specialization of phagocytic ameboid cells may have impaired regenerative capacities in metazoan lineages.

Animal regeneration is a fascinating field of research that has captured the attention of many generations of scientists. Among the cellular mechanisms underlying tissue and organ regeneration, we highlight the role of phagocytic ameboid cells (PACs). Beyond their ability to engulf nutritional particles, microbes, and apoptotic cells, their involvement in regeneration has been widely documented. It has been extensively described that, at least in part, animal regenerative mechanisms rely on PACs that serve as a hub for a range of critical physiological functions, both in health and disease. Considering the phylogenetics of PAC evolution, and the loss and gain of nutritional, immunological, and regenerative potential across Metazoa, we aim to discuss when and how phagocytic activity was first co-opted to regenerative tissue repair. We propose that the gradual specialization of PACs during metazoan derivation may have contributed to the loss of regenerative potential in animals, with critical impacts on potential translational strategies for regenerative medicine.