TET2 (TET oncogene family member 2) is a candidate tumor suppressor gene located at chromosome 4q24, and was recently reported to be mutated in ~14% of patients with JAK2 V617F-positive myeloproliferative neoplasms. We used high-throughput DNA sequence analysis to screen for TET2 mutations in bone marrow-derived DNA from 48 patients with systemic mastocytosis (SM), including 42 who met the 2008 WHO (World Health Organization) diagnostic criteria for SM and 6 with FIP1L1-PDGFRA. Twelve (29%) SM, but no FIP1L1-PDGFRA patients, had TET2 mutations. A total of 17 mutations (13 frameshift, 2 nonsense and 2 missense) were documented in 2 (15%) of 13 indolent SM patients, 2 (40%) of 5 aggressive SM, and 8 (35%) of 23 SM associated with a clonal non-mast cell-lineage hematopoietic disease (P = 0.52). KITD816V was detected by PCR sequencing in 50 or 20% of patients with or without TET2 mutation (P = 0.05), respectively. Multivariable analysis showed a significant association between the presence of TET2 mutation and monocytosis (P = 0.0003) or female sex (P = 0.05). The association with monocytosis was also observed in non-indolent SM (n = 29), in which the presence of mutant TET2 did not affect survival (P = 0.98). We conclude that TET2 mutations are frequent in SM, segregate with KIT D816V and influence phenotype without necessarily altering prognosis.
The retinal projection to the brain in Xenopus has been examined using autoradiographic techniques. The labelled moieties used were 3H-proline and 3H-fucose. There are three anterior thalamic optic terminal sites in Xenopus. These are the nucleus of Bellonci, the corpus geniculatum thalamicum and the rostral visual nucleus. The first two of these are similar to the homonymous nuclei in Rana while the last, the rostral visual nucleus, appears to correspond to the rostral end of the posterior entopeduncular nucleus of Rana. Both the nucleus of Bellonci and the rostral visual nucleus receive strong ipisilateral retinal inputs while the corpus geniculatum receives only a weak ipsilateral projection. In the posterior thalamic: pretectal region there is only one clearly defined optic terminal nucleus--the uncinate field. This structure receives a strong ipsilateral input. In addition there are two other labelled fields in this region whose nature (fibers v. terminals) cannot be clearly discerned in autoradiographs. These are the thalamopretectal field--a horizontal band which extends in the dorsomedial neuropil from midthalamus to the pretectum, and the pretectal field where diffuse labelling is evident, especially ipsilateral to the injected eye. The thalamopretectal field also receives an ipsilateral input. The optic tectum in Xenopus receives a dense contralateral retinal innervation but only a weak ipsilateral projection. Finally, the basal optic nucleus receives both contralateral and ipsilateral retinal innervation with the latter being, by far, the weaker of the two. In addition to other differences between the two species, it is obvious that there is a much denser and more extensive ipsilateral retinal projection to the thalamic and pretectal brain structures in Xenopus than in Rana. This is presumably due to the greater size of the binocular field in Xenopus.
Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterized by chronic proliferation of hematopoietic progenitors. We studied the telomere length (TL) of 335 MPN patients and 93 gender- and age-matched controls using a quantitative PCR method (relative TL calculated as the ratio of the amount of telomere DNA vs single-copy DNA: T/S ratio). TL was markedly reduced in MPN patients compared with controls (T/S 0.561 vs 0.990, P<0.001). In JAK2V617F MPN patients, TL correlated inversely with allelic burden (P<0.001). Patients homozygous for the mutation (allelic burden 90–100%) had the shortest TL, even when compared with patients with lower allele burdens consistent with a dominant heterozygous population (allelic burden 55–65%) (T/S 0.367 vs 0.497, P = 0.037). This suggests that the high degree of proliferation of the MPN clone reduces TL and suggests the possibility that TL shortening may be indicative of progressive genomic instability during MPN progression. The TL of JAK2V617F-negative MPN patients was similar to JAK2V617F-positive counterparts (T/S 0.527 vs 0.507, P = 0.603), suggesting that the yet-to-be-discovered causative mutation(s) impact the mutated stem cell similarly to JAK2V617F, and that TL measurement may prove useful in the diagnostic workup of JAK2V617F-negative MPN.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.