Junctional adhesion molecule C (JAM-C) distinguishes CD27+ germinal center B lymphocytes from non-germinal center cells and constitutes a new diagnostic tool for B-cell malignancies.

Differentiation of naïve B cells into plasma cells or memory cells occurs in the germinal centers (GCs) of lymph follicles or alternatively via a GC- and T-cell-independent pathway. It is currently assumed that B-cell lymphomas correlate to normal B-cell differentiation stages, but the precise correlation of several B-cell lymphomas to these two pathways remains controversial. In the present report, we describe the junctional adhesion molecule C (JAM-C), currently identified at the cell-cell border of endothelial cells, as a new B-cell marker with a tightly regulated expression during B-cell differentiation. Expression of JAM-C in tonsils allows distinction between two CD27+ B-cell subpopulations: JAM-C- GC B cells and JAM-C+ non-germinal B cells. The expression of JAM-C in different B-cell lymphomas reveals a disease-specific pattern and allows a clear distinction between JAM-C- lymphoproliferative syndromes (chronic lymphocytic leukemia, mantle cell lymphoma and follicular lymphoma) and JAM-C+ ones (hairy cell leukemia, marginal zone B-cell lymphoma). Therefore, we propose JAM-C as a new identification tool in B-cell lymphoma diagnosis.

Lentiviral PU.1 overexpression restores differentiation in myeloid leukemic blasts.

PU.1, a transcription factor of the ETS family, plays a pivotal role in normal hematopoiesis, and particularly in myeloid differentiation. Altered PU.1 function is possibly implicated in leukemogenesis, as PU.1 gene mutations were identified in some patients with acute myeloid leukemia (AML) and as several oncogenic products (AML1-ETO, promyelocytic leukemia-retinoic acid receptor alpha, FMS-like receptor tyrosine kinase 3 internal tandem duplication) are associated with PU.1 downregulation. To demonstrate directly a role of PU.1 in the blocked differentiation of leukemic blasts, we transduced cells from myeloid cell lines and primary blasts from AML patients with a lentivector encoding PU.1. In NB4 cells we obtained increases in PU.1 mRNA and protein, comparable to increases obtained with all-trans retinoic acid-stimulation. Transduced cells showed increased myelomonocytic surface antigen expression, decreased proliferation rates and increased apoptosis. Similar results were obtained in primary AML blasts from 12 patients. These phenotypic changes are characteristic of restored blast differentiation. PU.1 should therefore constitute an interesting target for therapeutic intervention in AML.

Efficacy of monolayer preparations for cervical cytology: emphasis on suboptimal specimens.

OBJECTIVE: To compare specimen adequacy and detection of disease in conventional cytologic smears and CytoRich monolayer preparations. STUDY DESIGN: Five hundred sixty pairs of conventional smears and monolayer preparations were compared. The conventional smear was made first, and the remaining cells were rinsed off into a vial containing transport medium. Monolayer slides were then prepared using the CytoRich system. RESULTS: Evaluation of cases for specimen adequacy based on the Bethesda System demonstrated that the CytoRich method eliminated preparations of poor quality, reducing significantly the number of suboptimal specimens (28.3% for conventional vs. 8.4% for CytoRich). The final diagnosis concurred in 82.8% of cases. In 8 cases the CytoRich slide showed a low grade or more severe lesion, while the conventional smear was "atypical" (ASCUS) in 7 cases of squamous intraepithelial lesion and unsatisfactory in 1 case of invasive carcinoma. In three cases the conventional smear showed a low or high grade lesion, while the CytoRich slide was atypical. CONCLUSION: The CytoRich method significantly reduces suboptimal preparations and the associated ambiguous or inconsistent diagnoses. It detects cervical abnormalities better than does the conventional smear. It may result in cost savings for the community and benefit patients since unnecessary recalls are avoided.