In vitro and in vivo effects of JAK2 inhibition in chronic myelomonocytic leukemia

In chronic myelomonocytic leukemia (CMML), colony‐forming units granulocyte/macrophage (CFU‐GM), which grow in vitro in the absence of exogenous growth factors, arise from the abnormal clone that is responsible for the overproduction of granulomonocytic cells. Previous in vitro findings including ours suggest that divergent molecular aberrations in CMML seem to converge within the GM‐CSF signaling pathway. As JAK2 is a sentinel kinase in this pathway, JAK2 inhibition may be an attractive treatment approach in CMML. We investigated the in vitro effects of the specific JAK2 inhibitor TG101209 on the autonomous CFU‐GM formation from peripheral blood mononuclear cells of patients with CMML. TG101209 was found to either block or strongly inhibit spontaneous CFU‐GM growth in all 10 patients tested. This inhibitory effect was dose dependent and significantly more pronounced as compared to the inhibitory effect on stimulated CFU‐GM growth from normal individuals. In a CMML patient with splenomegaly, who was treated with the JAK1/2 inhibitor ruxolitinib off label, we can demonstrate a spleen response and the disappearance of constitutional symptoms which was associated with a decrease in autonomous CFU‐GM formation ex vivo. Pharmacological JAK2 inhibition may be an interesting approach to be systematically studied in patients with CMML.     

An Investigation of the “Jumping to Conclusions” Data-Gathering Bias and Paranoid Thoughts in Asperger Syndrome

The existence of a data-gathering bias, in the form of jumping to conclusions, and links to paranoid ideation was investigated in Asperger syndrome (AS). People with AS (N = 30) were compared to a neurotypical control group (N = 30) on the Reading the Mind in the Eyes and the Beads tasks, with self-report measures of depression, general anxiety, social anxiety, self-consciousness and paranoid ideation. The AS group performed less well than the control group on the Reading the Mind in the Eyes Task with regard to accuracy but responded more quickly and tended to make decisions on the basis of less evidence on the Beads Task with 50 % demonstrating a clear ‘jumping to conclusions bias’, whereas none of the control group showed such a bias. Depression and general anxiety were associated with paranoid ideation but not data-gathering style, which was contrary to expectation.     

Metastasentherapie bei malignem Melanom mit unbekanntem Primärtumor

Malignant melanoma from unknown primary tumor is always a metastatic tumorous disease. The clinical presentation is often regional tumor manifestations in skin, subcutis, soft tissue or lymph nodes but may also show visceral metastases in lungs, liver, brain, bones, spleen or gastrointestinal manifestations. Diagnosis and treatment cannot always be separated. As multiple sites are frequently involved the individual treatment plan should be devised by an interdisciplinary tumor board after whole body staging. Documented local metastases in skin, soft tissue or lymph nodes are classified as stage III melanoma and treated accordingly. The prognosis has been shown to be equal to or even better than in cases with known primary tumor. Even after curative resection further recurrences are common but can often be re-resected with curative intent. Palliative treatment options, such as interventional procedures, radiotherapy, chemotherapy, novel kinase inhibitors and immunotherapy depend on tumor extent and the sites of the metastases.