Hedgehog (HH) signaling is activated in various lymphoid malignancies, but conflicting results exist about 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 SMOOTHENED (SMO) inhibitors, whereas 40% were completely resistant. Responsiveness correlated with elevated GLI1 and PTCH1 transcript levels and the presence of trisomy 12, whereas no other karyotype correlated with responsiveness. All trisomy 12 CLLs displayed constitutive HH pathway activation driven by autocrine DESERT HH (DHH) ligand secretion, which could be blocked by the HH-blocking Ab 5E1. Cocultures with DHH-expressing BM stromal c...

Authors: Stephens D, Ruppert AS, Blum K, Jones J, Flynn J, Johnson A, Ji J, Phelps M, Grever M, Byrd J Abstract Older chronic lymphocytic leukemia patients have poor outcomes with standard treatments and are underrepresented in clinical trials. We retrospectively reviewed outcomes of refractory chronic lymphocytic leukemia patients in two age categories [≥70, <70 years] treated with single-agent flavopiridol, a drug active in genomically high-risk patients, during two trials. No significant difference between older and younger patients was observed in response rates (43% versus 47%) or progression-free survival (median=8.7 versus 9.9 months, p>0.80). Although overall survival was worse in older patients (median=2.1 versus 2.4 years, p=0.02), when adjusted for other factors,...

Studies focused on treatment of Chronic Lymphocytic Leukemia (CLL) recognized by the American Society of Hematology (Source: McKesson News)

Krishnakumar Rathnam, Shashidhar Karpurmath, Sanju Cyriac, Sagar Tenali Gnana, Shirley SundersinghJournal of Cancer Research and Therapeutics 2011 7(4):484-485 (Source: Journal of Cancer Research and Therapeutics)

Authors: Molica S, Gentile M, Mauro FR, Brugiatelli M, Federico M, Sperduti I, Neri A, Ferrarini M, Foà R, Morabito F Abstract No abstract available. PMID: 22262125 [PubMed - as supplied by publisher] (Source: Acta Haematologica)