絞り込み

18440

広告

温暖化対策強化、100人分訴え (毎日新聞)

若者グループが25日夕、政府などに地球温暖化対策の強化を訴える活動を全国各地で行った。東京都千代田区の国会前では、「迫り来るタイムリミット」「石炭だめ」などのメ...

  1. 新型コロナ GoTo事業者、来月募集 「...
  2. 検証:異常気象、新たな日常 米で熱波/北...
  3. 新型コロナ 全国新たに576人 (毎日新...
  4. 新型コロナ 接種主体は市町村に ワクチン...

ニュース一覧

Trisomy 12 and elevated GLI1 and PTCH1 transcript levels are biomarkers for Hedgehog-inhibitor responsiveness in CLL.

著者 Decker S , Zirlik K , Djebatchie L , Hartmann D , Ihorst G , Schmitt-Graeff A , Herchenbach D , Jumaa H , Warmuth M , Veelken H , Dierks C
Blood.2011 Nov 30 ; ():.
この記事をPubMed上で見るPubMedで表示
この記事をGoogle翻訳上で見る Google翻訳で開く

University Medical Center Freiburg, Department of Hematology/Oncology, Freiburg, Germany;

スターを付ける スターを付ける     (109view , 0users)
Hedgehog (HH) signaling is activated in various lymphoid malignancies, but conflicting results exist regarding its role in chronic lymphocytic leukemia (CLL). Here, we demonstrate that the expression of essential HH pathway components like GLI1, PTCH1 and the HH ligands is highly diverse in CLL. A subset of 36.7% of 60 tested CLL samples responded to all 3 SMO-inhibitors, while 40% were completely resistant. Responsiveness correlated with elevated GLI1 and PTCH1 transcript levels and the presence of trisomy 12, while no other karyotype correlated with responsiveness. All trisomy 12 CLLs displayed constitutive HH pathway activation driven by autocrine DHH ligand secretion, which could be blocked by the HH-blocking antibody 5E1. Cocultures with DHH expressing bone marrow stromal cells reduced sensitivity of CLLs to SMO-inhibitor treatment by activation of non-canonical ERK-phosphorylation directly downstream of the PTCH1-receptor without involvement of SMO and could be overcome by the HH-blocking antibody 5E1 or a combination of SMO- and ERK-inhibitors. Our results demonstrate that the HH signaling pathway is an interesting therapeutical target for a subset of CLL patients, characterized by high GLI1 and PTCH1 transcript levels and all trisomy 12 patients and indicates HH-blocking antibodies to be favourable over SMO-inhibitors in overcoming stroma-mediated protective effects.
PMID: 22130798 [PubMed - as supplied by publisher]
印刷用ページを開く Endnote用テキストダウンロード