Lymphatics

In the original publication [...]

Chronic lymphocytic leukemia (CLL) is an indolent malignancy with modest proliferation in the lymph nodes and accumulation of quiescent B cells in the peripheral blood. Targeted agents, including BTK inhibitors such as ibrutinib and the BCL2 antagonist venetoclax, have transformed therapy by disrupting proliferation, survival, and lymph node retention of CLL cells, yet CLL remains incurable. Recent studies reveal that CLL cells exist along a spectrum of proliferating, activated, and quiescent states, with dynamic transitions that shape intraclonal behavior. Whilst proliferation occurs mainly in lymph nodes, most emigrant cells in the peripheral blood become quiescent, with only a minority remaining activated. Quiescent, activated, and proliferating fractions display distinct phenotypes and CXCR4 and CD5 levels can be used to distinguish these states in the CLL life cycle. While proliferating and activated cells are more susceptible to BTK inhibition, quiescent subsets show greater sensitivity to BCL2 blockade. These functional differences, together with emerging evidence that phenotypic markers may correlate with residual disease activity, point to potential translational significance. Understanding how CLL cells switch between proliferative, activated and quiescent states will be important to uncover novel vulnerabilities and inform rational treatment strategies.

Lymphatic malformations are rare congenital anomalies that range from small, self-limited lesions to large, rapidly expanding masses capable of causing serious perinatal complications, including hydrops fetalis, polyhydramnios, airway obstruction, and fetal demise. Although most lesions are managed expectantly or postnatally, in utero interventions have been attempted in highly select cases where lesions threaten pregnancy viability or safety of delivery. Reported approaches include the perinatal option of ex utero intrapartum therapy, intrauterine ultrasound-guided cyst aspiration for decompression, intrauterine intralesional sclerotherapy with agents such as OK-432, and more recently, maternal pharmacologic therapy targeting the mTOR pathways. This review summarizes the available literature describing prenatal management of these lesions, including procedural techniques, maternal and fetal outcomes, and emerging strategies. Together, these findings highlight the potential promise and the caution necessary in translating postnatal therapeutic advances for lymphatic malformations to the prenatal setting.