F diffuse large B cell lymphoma-associated antigen-specific V6/V13+T cells by TCR gene transfer. J Hematol Oncol 2011, 4:2. Ochi T, Fujiwara H, Okamoto S, Asai H, Miyazaki Y, Shirakata T, Mineno J, Kuzushima K, Shiku H, Yasukawa M: Redirected CD4+ T Cells Using WT1Specific T-Cell Receptor Gene Transfer Can Supply Multifactorial Help to Enhance the Anti-Leukemia Reactivity Mediated by Similarly Redirected CD8+ T Cells Using the Identical Gene Transfer. ASH Annual Meeting Abstracts 2011, 118(21):#645. Terakura S, Yamamoto TN, Gardner RA, Turtle CJ, Jensen MC, Riddell SR: Generation and Signaling Function of CD19 Chimeric Antigen Receptor Modified CD8+ T Cells Derived From Virus-Specific Central Memory Cells for Adoptive Therapy After Allogeneic Hematopoietic Stem Cell Transplant. ASH Annual Meeting Abstracts 2011, 118(21):#2978. Cartellieri M, Michalk I, von Bonin M, Kr er T, Stamova S, Koristka S, Arndt C, Feldmann A, Schmitz M, Wermke M, et al: Chimeric Antigen Receptor-Engineered T Cells for Immunotherapy of Acute Myeloid Leukemia. ASH Annual Meeting Abstracts 2011, 118(21):#2618.doi:10.1186/1756-8722-5-S1-A3 Cite this article as: Li: T-cell immunodeficiency and reconstruction based on TCR rearrangement analysis in hematological malignancy: update from 2011 ASH annual meeting. Journal of Hematology Oncology 2012 5(Suppl 1):A3.
Pan Journal of Hematology Oncology 2012, 5(Suppl 1):A6 http://www.jhoonline.org/content/5/S1/AJOURNAL OF HEMATOLOGY ONCOLOGYMEETING ABSTRACTOpen AccessOvercoming Gleevec-resistance by blocking oncogene addiction in malignant hematologic cellsJingxuan Pan From New developments in Hematology and Oncology in 2011 Guangzhou, China. 25-26 DecemberIn PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28945807 some types of tumors, malignant cells are highly dependent on the constitutive activation of a certain protein encoded by oncogene, despite existence of additional carcinogenic genetic changes. This phenomenon is referred to oncogene addiction. Typical examples include cytoplasmic tyrosine kinase Bcr-Abl in chronic myeloid leukemia (CML), receptor tyrosine kinase KIT in systemic mastocytosis and gastrointestinal stromal tumors (GISTs), and PDGFRa in hypereosinophilic syndrome (HES). In 2001, the approval of Gleevec (STI571, imatinib mesylate, order Necrostatin-1 Norvartis) by FDA (Food and Drug Administration, USA) initiated a revolutionary targeted therapy against cancer with small molecule tyrosine kinase inhibitors. Gleevec blocks the signaling pathway of tyrosine kinase by competitively occupying the ATP-binding pocket of Bcr-Abl, KIT and PDGFRa, and therefore kills these oncogene-addicted tumor cells. Patients with CML and HES have gained much better prognosis with the treatment of Gleevec. However, in some patients (particularly in accelerating and blast crisis phases), relapse due to resistance to Gleevec is an emerging problem. Acquired point mutations within the target genes (Bcr-Abl, KIT and PDGFRa) are a major mechanism of resistance to Gleevec in some patients with hematologic malignance. The mutations are believed to block the binding of Gleevec to ATP binding pockets of these tyrosine kinases. In this case, novel tyrosine kinase inhibitor such as nilotinib and dasatinib (also called the second-generation of tyrosine kinase inhibitor) have been shown activity against Gleevec-resistant patients bearing some point mutations but the “gate-keeper” mutations (e.g., T315I Bcr-Abl, T674I PDGFRa).Therefore, development of more novel small molecule tyrosine kinase inhibitors is still.
