Twelve years of follow up of cases with old 241Am internal contamination.

A group of workers internally contaminated with Am have been followed for about 12 years. The source of contamination was AmO2 powder used for production of AmBe neutron sources and other applications. The production of some radionuclide sources included chemical treatment of the original material, which transformed the americium into the nitrate, but mostly powder metallurgy was used for production of sources for smoke detectors. In vivo measurement of the workers was performed with two LEGe detectors placed near the head of the measured person. Calibration was performed with four different physical skull phantoms of different origin and a voxel phantom with Monte Carlo simulation, which was developed to fit the head sizes of individual persons. Samples of urine and feces were analyzed by means of radiochemical separation followed by alpha-spectrometry. Separation of 241Am from mineralized excreta was performed by combined anion exchange and extraction chromatographic techniques. As a tracer, 243Am was used. When the measured data (83 data on skeletal activity, activity in 389 bioassay samples) were compared with International Commission on Radiological Protection's and Leggett's biokinetic models of americium, it was found that in most cases, after more than 15 y since the intake, the excretion rate was lower (or skeletal activity higher) than predicted. On the other hand, the ratio of excreted activity in urine and feces agrees well with model predictions.

Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas.

The genetics of t(11;14)(q13;q32)/cyclin D1-negative mantle cell lymphoma (MCL) is poorly understood. We report here 8 MCL cases lacking t(11;14) or variant CCND1 rearrangement that showed expression of cyclin D1 (2 cases), D2 (2 cases), and D3 (3 cases). One case was cyclin D negative. Cytogenetics and fluorescence in situ hybridization detected t(2;12)(p11;p13)/IGK-CCND2 in one of the cyclin D2-positive cases and t(6;14)(p21;q32)/IGH-CCND3 in one of the cyclin D3-positive cases. Moreover, we identified a novel cryptic t(2;14)(p24;q32) targeting MYCN in 2 blastoid MCLs: one negative for cyclin D and one expressing cyclin D3. Interestingly, both cases showed expression of cyclin E. Notably, all 3 blastoid MCLs showed a monoallelic deletion of RB1 associated with a lack of expression of RB1 protein and monoallelic loss of p16. In sum-mary, this study confirms frequent aberrant expression of cyclin D2 and D3 in t(11;14)-negative MCLs and shows a t(11;14)-independent expression of cy-clin D1 in 25% of present cases. Novel findings include cyclin E expression in 2 t(11;14)-negative MCLs characterized by a cryptic t(2;14)(p24;q32) and identification of MYCN as a new lymphoma oncogene associated with a blastoid MCL. Clinically important is a predisposition of t(11;14)-negative MCLs to the central nervous system involvement.

Telomeric IGH losses detectable by fluorescence in situ hybridization in chronic lymphocytic leukemia reflect somatic VH recombination events.

Routine interphase fluorescence in situ hybridization (FISH) analysis of chronic lymphocytic leukemia (CLL) with LSI IGH/CCND1 assay, applied to differentiate CLL from leukemic mantle cell lymphoma, identified a subset of cases (42/174) with translocation-like IGH signal pattern. To unravel the underlying 14q32/IGH aberrations, 14 of these cases were subjected to cytogenetic, detailed FISH, and V(H) mutation analyses. FISH identified cryptic losses of various portions of the IGHV region in all 14 cases. Fine mapping of these V(H) deletions revealed a strict correlation between their distal border and localization of the used VH gene, suggesting that they are not oncogenic but reflect physiological events accompanying somatic V-D-J assembly. This hypothesis was further supported by FISH analysis of 20 CLL and hairy cell leukemia cases with the known V(H) usage showing a constant loss of sequences proximal to the used gene, identification of V(H) deletions in normal B cells, and their exclusive demonstration in B cell malignancies, but not of T cell and myeloid linage. Given that these cryptic physiological VH losses in B cells may seriously complicate analysis of B cell leukemia/lymphoma and lead to false conclusions, FISH users should take them into consideration when interpreting IGH aberrations in these malignancies.