Although patients with aggressive non-Hodgkins's lymphoma (NHL) can be cured with combination chemotherapy, over 50% of these patients still die of their disease. Despite the inclusion of additional active agents and modification of drug doses and schedules, we have not made a significant impact on the upfront therapy of this curable disease in 15 years. Although we have developed clinical prognostic factor models that help us distinguish curable patients from ones who are unlikely to benefit from current regimens, these models are imprecise. We believe the imprecision is due to the fact that the clinical factors are only surrogate markers for the cellular and molecular heterogeneity of this disease. To further characterize cellular and molecular heterogeneity in aggressive NHL, we will identify and specifically treat patients with high-risk aggressive NHL, making use of newly defined clinical and molecular markers and experimental treatment regimens (Specific Aim 1). We will also define additional cellular featrues that reflect the biological heterogeneity of aggressive NHL, focusing on specific aspects of tumor cell trafficking (CD44 isoform expression) and tumor cell immunogenicity (pHTCL and pCTCL) (Specific Aim 2). Finally, we will identify novel molecular markers of the biological heterogenicity of aggressive NHL using """"""""high-"""""""" and """"""""low-risk"""""""" patient tumor samples and the recently described technique of differential display (Specific Aim 3). The success of this project is highly dependent upon the coordinated efforts of the indicated investigators, program collaborators, expert clinicians and core personnel.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
1P01CA066996-03
Application #
6269698
Study Section
Project Start
1998-05-14
Project End
1999-03-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215
Hogan, Louise E; K├Ârner, Christian; Hobbs, Kristen et al. (2018) NK-cell activation is associated with increased HIV transcriptional activity following allogeneic hematopoietic cell transplantation. Blood Adv 2:1412-1416
Kelly, Rachel S; Lasky-Su, Jessica; Yeung, Sai-Ching J et al. (2018) Integrative omics to detect bacteremia in patients with febrile neutropenia. PLoS One 13:e0197049
Nakamura, Makoto; Wu, Lizi; Griffin, James D et al. (2018) Notch1 activation enhances proliferation via activation of cdc2 and delays differentiation of myeloid progenitors. Leuk Res 72:34-44
Gechijian, Lara N; Buckley, Dennis L; Lawlor, Matthew A et al. (2018) Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands. Nat Chem Biol 14:405-412
Chu, S Haihua; Song, Evelyn J; Chabon, Jonathan R et al. (2018) Inhibition of MEK and ATR is effective in a B-cell acute lymphoblastic leukemia model driven by Mll-Af4 and activated Ras. Blood Adv 2:2478-2490
Sridhar, Radhakrishnan; Takei, Hisashi; Syed, Riyaz et al. (2018) Styryl Quinazolinones as Potential Inducers of Myeloid Differentiation via Upregulation of C/EBP?. Molecules 23:
Sievers, Quinlan L; Gasser, Jessica A; Cowley, Glenn S et al. (2018) Genome-wide screen identifies cullin-RING ligase machinery required for lenalidomide-dependent CRL4CRBN activity. Blood 132:1293-1303
Wang, Jinhua; Erazo, Tatiana; Ferguson, Fleur M et al. (2018) Structural and Atropisomeric Factors Governing the Selectivity of Pyrimido-benzodiazipinones as Inhibitors of Kinases and Bromodomains. ACS Chem Biol 13:2438-2448
Fathi, Amir T; Erba, Harry P; Lancet, Jeffrey E et al. (2018) A phase 1 trial of vadastuximab talirine combined with hypomethylating agents in patients with CD33-positive AML. Blood 132:1125-1133
Cortes, Jorge E; Douglas Smith, B; Wang, Eunice S et al. (2018) Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results. Am J Hematol 93:1301-1310

Showing the most recent 10 out of 376 publications