Megakaryocytes, erythropoietic and granulopoietic cells express CAL2 antibody in myeloproliferative neoplasms carrying CALR gene mutations.

Testing for the CALR mutation is included in the updated WHO criteria for essential thrombocythaemia (ET) and primary myelofibrosis (PMF). We report on the application of the CAL2 monoclonal antibody, raised against the mutated CALR gene to myeloid cases. The immunostain was used on 116 acute myeloid leukaemias (AML) and 66 myeloproliferative neoplasms (MPN) or myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN). None of AML cases was stained by the CAL2 antibody, while 20/66 MPNs and MDS/MPNs appeared positive. Fourteen of the latter cases were studied by molecular techniques, and all showed aberrations of the CALR gene. In addition, CAL2 positivity was found in some small-sized elements besides megakaryocytes. By double staining, these elements corresponded to small megakaryocytes as well as both erythroid and myeloid precursors. This finding suggests possible occurrence of CALR gene abnormalities in a stem cell.

Upregulated Akt signaling adjacent to gastric cancers: implications for screening and chemoprevention.

Most gastric adenocarcinomas arise as a longterm complication of Helicobacter pylori infection of the stomach, but the high prevalence of this infection limits the cost-effectiveness of antibiotic eradication as a cancer prevention strategy. Here we have used phosphorylation-specific antibodies against the Akt kinase consensus sequence to detect downstream substrates of this oncogenic signaling pathway in normal and malignant gastric tissues. In vitro studies confirm that phosphorylation of Akt and its substrates is inducible by epithelial mitogens such as epidermal growth factor (EGF), which is implicated in the pathogenesis of H. pylori gastritis. Control clinical studies confirm far stronger Akt substrate phosphorylation in primary human breast cancers than in matched adjacent normal breast tissues; unexpectedly, however, increased Akt signaling is apparent in both primary stomach cancers and adjacent normal gastric tissues. These findings raise the possibility of a preneoplastic field defect induced in morphologically normal tissues, and suggest that immunoassays of mucosal Akt activity could guide preventive surveillance and/or intervention in patients at risk of gastric cancer. Moreover, since recent reports confirm Akt inhibition by COX-2 inhibitors, these data support the chemopreventive efficacy of such drugs for at-risk individuals.