Jonathan H Schatz

Learn More
Molecular mechanisms underlying the coordination of isotype switching with plasma cell differentiation are poorly understood. We show that interferon regulatory factor-4 (IRF-4) regulates both processes by controlling the expression of the Aicda and Prdm1 genes, which encode AID and Blimp-1, respectively. Genome-wide analysis demonstrated that Irf4(-/-) B(More)
New anticancer drugs that target oncogenic signaling molecules have greatly improved the treatment of certain cancers. However, resistance to targeted therapeutics is a major clinical problem and the redundancy of oncogenic signaling pathways provides back-up mechanisms that allow cancer cells to escape. For example, the AKT and PIM kinases produce parallel(More)
The translational control of oncoprotein expression is implicated in many cancers. Here we report an eIF4A RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of silvestrol and related compounds. For example, eIF4A promotes T-cell acute lymphoblastic leukaemia development in vivo and(More)
The genetics of angioimmunoblastic T-cell lymphoma (AITL) are very poorly understood. We defined the mutational landscape of AITL across 219 genes in 85 cases from the United States and Europe. We identified ≥2 mutations in 34 genes, nearly all of which were not previously implicated in AITL. These included loss-of-function mutations in TP53 (n = 4), ETV6(More)
Insights into cancer genetics can lead to therapeutic opportunities. By cross-referencing chromosomal changes with an unbiased genetic screen we identify the ephrin receptor A7 (EPHA7) as a tumor suppressor in follicular lymphoma (FL). EPHA7 is a target of 6q deletions and inactivated in 72% of FLs. Knockdown of EPHA7 drives lymphoma development in a murine(More)
Signaling by the PI3K/AKT/mTOR pathway is frequently deregulated in non-Hodgkin's lymphoma (NHL), prompting evaluation of the rapamycin-analog (rapalog) mTOR inhibitors in multiple clinical trials. The drugs show activity as single agents, and the rapalog temsirolimus is now accepted as a therapeutic option in relapsed/refractory mantle cell lymphoma.(More)
Better treatments are needed for patients with diffuse large B-cell lymphoma (DLBCL) at high risk of failing standard therapy. Avoiding apoptosis is a hallmark of cancer, and in DLBCL the redundantly functioning antiapoptotic proteins BCL2 and MCL1 are frequently expressed. Here we explore drugs that cause loss of MCL1, particularly the potent new(More)
Interferon regulatory factor 4 (IRF-4) plays important functions in B- and T-cell development and immune response regulation and was originally identified as the product of a proto-oncogene involved in chromosomal translocations in multiple myeloma. Although IRF-4 is expressed in myeloid cells, its function in that lineage is not known. The closely related(More)
PCT onset by ~ 50%, it is likely that targeting IL-6 production in human bone marrow stromal cells would slow the transition from MGUS to frank MM with similar efficiency, potentially preventing many cases of newly diagnosed disease. The adoptive cell transfer approach described here can be readily extended to studies on other myeloma drivers that govern(More)
Loss of cell cycle controls is a hallmark of cancer and has a well-established role in aggressive B cell malignancies. However, the role of such lesions in indolent follicular lymphoma (FL) is unclear and individual lesions have been observed with low frequency. By analyzing genomic data from two large cohorts of indolent FLs, we identify a pattern of(More)