Langerhans cell histiocytosis (LCH) is a rare systemic disorder characterized by the accumulation ofCD1a+/Langerin+LCHcells and wide‐ranging organ involvement. Langerhans cell histiocytosis was formerly referred to as histiocytosis X, until it was renamed in 1987. Langerhans cell histiocytosis β was named for its morphological similarity to skin Langerhans cells. Studies have shown thatLCHcells originate from myeloid dendritic cells rather than skin Langerhans cells. There has been significant debate regarding whetherLCHshould be defined as an immune disorder or a neoplasm. A breakthrough in understanding the pathogenesis ofLCHoccurred in 2010 when a gain‐of‐function mutation inBRAF(V600E) was identified in more than half ofLCHpatient samples. Studies have since reported that 100% ofLCHcases showERKphosphorylation, indicating thatLCHis likely to be a clonally expanding myeloid neoplasm. Langerhans cell histiocytosis is now defined as an inflammatory myeloid neoplasm in the revised 2016 Histiocyte Society classification. Randomized trials and novel approaches have led to improved outcomes for pediatric patients, but no well‐defined treatments for adult patients have been developed to date. AlthoughLCHis not fatal in all cases, delayed diagnosis or treatment can result in serious impairment of organ function and decreased quality of life. This study summarizes recent advances in the pathophysiology and treatment of adultLCH, to raise awareness of this “orphan disease”.

Langerhans cell histiocytosis (LCH) is a rare disease characterized by clonal expansion of CD1a⁺CD207⁺ myeloid dendritic cells. The features of LCH are mainly described in children and remain poorly defined in adults; therefore, we conducted a nationwide survey to collect clinical data from 148 adult patients with LCH. The median age at diagnosis was 46.5 (range: 20–87) years with male predominance (60.8%). Among the 86 patients with detailed treatment information, 40 (46.5%) had single system LCH, whereas 46 (53.5%) had multisystem LCH. Moreover, 19 patients (22.1%) had an additional malignancy. BRAF V600E in plasma cell‐free DNA was associated with a low overall survival (OS) rate and the risk of the pituitary gland and central nervous system involvement. At a median follow‐up of 55 months from diagnosis, six patients (7.0%) had died, and the four patients with LCH‐related death did not respond to initial chemotherapy. The OS probability at 5 years post‐diagnosis was 90.6% (95% confidence interval: 79.8–95.8). Multivariate analysis showed that patients aged ≥60 years at diagnosis had a relatively poor prognosis. The probability of event‐free survival at 5 years was 52.1% (95% confidence interval: 36.6–65.5), with 57 patients requiring chemotherapy. In this study, we first revealed the high rate of relapse after chemotherapy and mortality of poor responders in adults as well as children. Therefore, prospective therapeutic studies of adults with LCH using targeted therapies are needed to improve outcomes in adults with LCH.

Venetoclax is an oral B-cell lymphoma-2 protein inhibitor. It is a key drug for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia. However, venetoclax is administered at a fixed dose, irrespective of body surface area or weight. Furthermore, the plasma concentration of venetoclax varies widely between individuals and is influenced by diet. Therefore, individualized dosing using therapeutic drug monitoring (TDM) may help to optimize treatment in clinical practice. In this study, we aimed to develop a simple method to determine venetoclax concentrations in plasma. The analysis required the extraction of a 50-μL plasma sample and precipitation of proteins using acetonitrile extraction. Venetoclax and the internal standard (12.5-μg/mL ibrutinib) were separated by high-performance liquid chromatography (HPLC). The calibration curve was linear over the plasma venetoclax concentration range 0.25–10 μg/mL with a coefficient of determination (r²) of 0.9999. The coefficients of intra-day and inter-day validation were 0.8–4.1% and 1.3–3.3%, respectively. The assay accuracy was −2.8 to 1.6%, and the recovery was >97.2%. These results demonstrate a very simple, novel and sensitive HPLC-UV-based method for determining the concentration of plasma venetoclax, and confirm its applicability to the TDM of venetoclax in a clinical setting.

The B820 subunit is an integral pigment−membrane protein complex and can be obtained by both dissociation of the core light-harvesting complex (LH1) in photosynthetic bacteria and reconstitution from its component parts in the presence of n-octyl β-d-glucopyranoside (OG). Intrinsic size of the B820 subunit from Rhodospirillum rubrum LH1 complex was measured by small-angle neutron scattering in perdeuterated OG solution and evaluated by Guinier analysis. Both the B820 subunits prepared by dissociation of LH1 and reconstitution from apopolypeptides and pigments were shown to have a molecular weight of 11 400 ± 500 and radius of gyration of 11.0 ± 1.0 Å, corresponding to a heterodimer consisting of one pair of αβ-polypeptides and two bacteriochlorophyll a molecules. Molecular weights of micelles formed by OG alone in solutions were determined in a range from 30 000 to 50 000 over concentrations of 1−5% (w/v), and thus are much larger than that of the B820 subunit. Similar measurement on the pigment-depleted apopolypeptides revealed highly heterogeneous behavior in the OG solutions, indicating that aggregates with various sizes were formed. The result provides evidence that bacteriochlorophyll a molecules play a crucial role in stabilizing and maintaining the B820 subunits in the dimeric state in solution. Further measurements on individual α- and β-polypeptides exhibited a marked difference in aggregation property between the two polypeptides. The α-polypeptides appear to be uniformly dissolved in OG solution in a monomeric form, whereas the β-polypeptides favor a self-associated form and tend to form large aggregates even in the presence of detergent. The difference in aggregation tendency was discussed in relation to the different behavior between α- and β-polypeptides in reconstitution with bacteriochlorophyll a molecules.