Research
The Hematologic Malignancies Program studies the epidemiology and progression of hematologic malignancies and develops new treatment strategies. Our program has three main research goals.
Investigating the epidemiology and mechanisms of progression for hematologic malignancies
Our research advances in this area include:
- Demonstrating that MYC locus rearrangements hijack super-enhancers to dysregulate MYC expression in multiple myeloma
- Demonstrating that suppression of uninvolved immunoglobulins defined by heavy/light chain pair suppression is a risk factor for progression of monoclonal gammopathy of undetermined significance (MGUS)
- Demonstrating that an elevated serum free light chain ratio may serve as a biomarker for malignant transformation in high-risk smoldering multiple myeloma
- Identifying circulating clonal plasma cells as a prognostic marker in smoldering multiple myeloma
- Showing that immunoglobulin free light chains are prognostic in T-cell and B-cell lymphoma
- Demonstrating that serum cytokine levels are prognostic, independent of the MIPI in mantle cell lymphoma
- Identifying plasma microvesicles as a new biomarker for chronic lymphocytic leukemia progression
- Validating CD49d as a key prognostic flow-based marker for disease outcome in chronic lymphocytic leukemia
- Showing that there's a marked increased risk of second cancers in monoclonal B-cell lymphocytosis similar to overt chronic lymphocytic leukemia
- Participating in the development and validation of an international prognostic index for patients with chronic lymphocytic leukemia (CLL-IPI)
- Showing the prognostic significance of mutation types and allele burden in myelofibrosis
- Developing MIPSS70, a mutation-enhanced international prognostic scoring system for patients with primary myelofibrosis
Characterizing the cell biology and molecular nature of hematologic malignancies to identify new therapeutic targets
Our research advances in this area include:
- Identifying cereblon binding proteins in multiple myeloma and mutations in cereblon pathway genes in refractory multiple myeloma
- Demonstrating that multiple myeloma cell capacity to degrade hydrogen peroxide determines lenalidomide sensitivity
- Demonstrating the role of IAP antagonists as immune adjuvants in the treatment of multiple myeloma in mice
- Demonstrating that RNA interference screening identifies lenalidomide sensitizers in multiple myeloma, including RSK2
- Conducting the first comprehensive comparisons of the frequency and distribution of molecular alterations in multiple myeloma tumors between African American and European American patients
- Conducting genome-wide studies in multiple myeloma that identified XPO1/CRM1 as a critical target validated using the selective nuclear export inhibitor KPT-276
- Developing unique drug resistant preclinical models (ibrutinib and bortezomib) in rare diseases such as Waldenstrom macroglobulinemia and identifying novel new therapeutic targets (USP14, UCHL5)
- Helping lead genome-wide association studies that identified susceptibility loci in large cell lymphoma
- Identifying inherited genetic variants that predict outcome in patients with diffuse large B-cell lymphoma treated with immunochemotherapy
- Demonstrating the relevance of the BTK and SYK pathways in lymphoma
- Identifying novel targetable gene fusions in T-cell lymphoma
- Showing that IRF4 is regulated by a novel CD30/NFkB feedback loop in T-cell lymphoma
- Determining that CCR8 is associated with DUSP22 rearrangements in anaplastic large cell lymphoma
- Showing that soluble PD-L1 is prognostic in diffuse large B-cell lymphoma
- Showing that TET-induced demethylation can be activated with ascorbic acid in large cell and T-cell lymphoma
- Demonstrating that CD38 is a novel therapeutic target in chronic lymphocytic leukemia
- Evaluating the genomic landscape of early-stage chronic lymphocytic leukemia
- Discovering a unique receptor tyrosine kinase target, Axl, for chronic lymphocytic leukemia
- Showing that histone deacetylase inhibitors reduce osteoblast-mediated protection of acute myeloid leukemia cells
Developing new therapies for hematologic malignancies
Our research advances in this area include:
- Establishing a cell therapy service line and research program for chimeric antigen receptor (CAR)-T cell therapy at all Mayo Clinic Comprehensive Cancer Center locations that helped support the CAR-T cell therapy program at Mayo Clinic
- Helping lead trials including bortezomib in frontline therapy for multiple myeloma
- Establishing updated criteria for diagnosis, response and minimal residual disease assessment in multiple myeloma
- Developing the Revised International Staging System for multiple myeloma
- Leading the initial studies of ixazomib alone and in combination in multiple myeloma
- Leading the first-in-human study of NEOD001, a monoclonal antibody targeting amyloidosis
- Finding that dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma
- Leading a phase III randomized trial of thalidomide plus zoledronic acid versus zoledronic acid alone in patients with asymptomatic multiple myeloma, providing the rationale for further studies in patients with smoldering multiple myeloma to delay chemotherapy
- Helping demonstrate that daratumumab in combination with bortezomib and dexamethasone resulted in significantly longer progression-free survival among patients with relapsed or relapsed and refractory multiple myeloma than did bortezomib and dexamethasone alone
- Demonstrating the effectiveness and safety of nivolumab in patients with previously heavily treated relapsed or refractory Hodgkin's lymphoma
- Demonstrating that brentuximab vedotin should not be given with bleomycin for patients with treatment naive, advanced stage Hodgkin's lymphoma
- Showing that R2CHOP shows promising efficacy in diffuse large B-cell lymphoma and that the addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome
- Determining the modest utility of post-therapy surveillance imaging in diffuse large B-cell lymphoma
- Determining that follicular transformation rates in the immunochemotherapy era are similar to risk of death without transformation
- Contributing to the development of new criteria to assess response to therapy in lymphoma
- Developing mTORC1 inhibitor therapy with RCHOP for untreated diffuse large B-cell lymphoma
- Establishing that vitamin D insufficiency predicts early clinical failure in follicular lymphoma
- Formulating guidelines for post-transplant lymphoproliferation disorders
- Helping to lead trials establishing the role of ibrutinib in chronic lymphocytic leukemia
- Developing a comprehensive prognostic index for patients with chronic lymphocytic leukemia
- Demonstrating that lenalidomide is not effective as first-line therapy for patients with chronic lymphocytic leukemia, particularly those who are elderly or frail, or both
- Demonstrating pembrolizumab selective activity in patients with chronic lymphocytic leukemia with Richter's transformation
- Showing that chemoimmunotherapy is bolstered with the use of an anti-VEGF agent in treating chronic lymphocytic leukemia
- Helping lead trials of blinatumomab in B-precursor acute lymphoblastic leukemia
- Showing the long-term efficacy and safety of momelotinib, a JAK1 and JAK2 inhibitor, in myelofibrosis
- Contributing to the development of CAR-T cells as a therapy for acute myeloid leukemia
- Demonstrating the efficacy of infliximab in steroid-refractory acute graft-versus-host disease