Genomes and Genes
P Leif Bergsagel
Affiliation: Mayo Clinic
- Molecular pathogenesis and a consequent classification of multiple myelomaP Leif Bergsagel
Comprehensive Cancer Center, Division of Hematology Oncology, Mayo Clinic, Scottsdale, AZ 85259, USA
J Clin Oncol 23:6333-8. 2005....
- MIP-1alpha (CCL3) is a downstream target of FGFR3 and RAS-MAPK signaling in multiple myelomaEsther Masih-Khan
Department of Medical Oncology, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada
Blood 108:3465-71. 2006..Our observation is the first to directly link an initiating IgH translocation not only to MM-cell growth and survival but also to the disease-associated bone disease...
- Cyclin D dysregulation: an early and unifying pathogenic event in multiple myelomaP Leif Bergsagel
Mayo Clinic Scottsdale, Comprehensive Cancer Center and Division of Hematology Oncology, Scottsdale, AZ, USA
Blood 106:296-303. 2005..However, despite subsequent progression events, these groups have differing gene expression profiles and also significant differences in the prevalence of bone disease, frequency at relapse, and progression to extramedullary tumor...
- Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosisJoseph R Mikhael
Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
Blood 119:4391-4. 2012..It is well tolerated with few side effects. CyBorD warrants continued investigation as treatment for AL...
- Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013Joseph R Mikhael
Division of Hematology Oncology, Mayo Clinic, Scottsdale, AZ 85259, USA
Mayo Clin Proc 88:360-76. 2013..This consensus statement reflects recommendations from more than 20 Mayo Clinic myeloma physicians, providing a practical approach for newly diagnosed patients with myeloma who are not enrolled in a clinical trial...
- Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomideYuan Xiao Zhu
Division of Hematology Oncology, Mayo Clinic, Scottsdale, AZ, USA
Blood 118:4771-9. 2011..In summary, CRBN is an essential requirement for IMiD activity and a possible biomarker for the clinical assessment of antimyeloma efficacy...
- Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activityRodger E Tiedemann
Mayo Clinic, Comprehensive Cancer Center, Division of Hematology and Oncology, Scottsdale, Arizona, USA
J Clin Invest 118:1750-64. 2008..These data support targeted repression of cyclin D genes as a therapeutic strategy for human malignancies...
- Lenalidomide, cyclophosphamide and dexamethasone (CRd) for newly diagnosed multiple myeloma: results from a phase 2 trialShaji K Kumar
Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
Am J Hematol 86:640-5. 2011..CRd is an effective and well-tolerated regimen for upfront therapy of MM with high response rates and excellent 2-year OS, and is suitable for long-term therapy...
- Clonal competition with alternating dominance in multiple myelomaJonathan J Keats
Comprehensive Cancer Center, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
Blood 120:1067-76. 2012..With the use of the Vk*MYC genetically engineered mouse model of myeloma we modeled this competition between subclones for predominance occurring spontaneously and with therapeutic selection...
- Evidence for cytogenetic and fluorescence in situ hybridization risk stratification of newly diagnosed multiple myeloma in the era of novel therapiePrashant Kapoor
Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA
Mayo Clin Proc 85:532-7. 2010..This study validates the high-risk features defined by FISH and CG in the Mayo risk-stratification model for patients with MM predominantly treated with novel therapies based on immunomodulatory agents...
- Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myelomaP Leif Bergsagel
Division of Hematology Oncology, Mayo Clinic in Arizona, Scottsdale, AZ 85259, USA
Blood 121:884-92. 2013..Reviewing available data in high-risk MM from this perspective, it appears that bortezomib has frequently been associated with improved survival, whereas thalidomide maintenance has sometimes been associated with a shorter survival...
- Drug response in a genetically engineered mouse model of multiple myeloma is predictive of clinical efficacyMarta Chesi
Comprehensive Cancer Center, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ, 85259, USA
Blood 120:376-85. 2012..We predict that combinations of standard agents, histone deacetylase inhibitors, bromodomain inhibitors, and hypoxia-activated prodrugs will demonstrate efficacy in the treatment of relapsed MM...
- Molecular pathogenesis of multiple myeloma: basic and clinical updatesMarta Chesi
Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ 85259, USA
Int J Hematol 97:313-23. 2013..Available evidence supports the use of a risk-stratified approach to the treatment of patients with multiple myeloma, with the early and prolonged use of bortezomib particularly in patients with t(4;14) and del 17p...
- Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelinesShaji K Kumar
Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
Mayo Clin Proc 84:1095-110. 2009..This set of recommendations represents such an effort-the development of a set of consensus guidelines by a group of experts to manage patients with newly diagnosed disease based on an interpretation of the best available evidence...
- AID-dependent activation of a MYC transgene induces multiple myeloma in a conditional mouse model of post-germinal center malignanciesMarta Chesi
Comprehensive Cancer Center, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA
Cancer Cell 13:167-80. 2008....
- Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tidesJan B Egan
Division of Hematology Oncology, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
Blood 120:1060-6. 2012....
- Diagnosis and management of Waldenström macroglobulinemia: Mayo stratification of macroglobulinemia and risk-adapted therapy (mSMART) guidelinesStephen M Ansell
Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
Mayo Clin Proc 85:824-33. 2010..Autologous stem cell transplant should be considered in all eligible patients with relapsed disease...
- Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenstrom's macroglobulinemiaEsteban Braggio
Mayo Clinic, Scottsdale, Arizona 85259 5494, USA
Cancer Res 69:3579-88. 2009....
- MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damage sitesHuadong Pei
Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA
Nature 470:124-8. 2011..Thus, we propose that a pathway involving γH2AX-MDC1-MMSET regulates the induction of H4K20 methylation on histones around DSBs, which, in turn, facilitates 53BP1 recruitment...
- Kinome-wide RNAi studies in human multiple myeloma identify vulnerable kinase targets, including a lymphoid-restricted kinase, GRK6Rodger E Tiedemann
Division of Hematology Oncology, Mayo Clinic Arizona, 13400 Shea Blvd, Scottsdale, AZ 85259, USA
Blood 115:1594-604. 2010..As mice that lack GRK6 are healthy, inhibition of GRK6 represents a uniquely targeted novel therapeutic strategy in human multiple myeloma...
- Gene expression profiling of pulmonary mucosa-associated lymphoid tissue lymphoma identifies new biologic insights with potential diagnostic and therapeutic applicationsWee J Chng
Department of Hematology Oncology, Comprehensive Cancer Center, Mayo Clinic, Scottsdale, AZ, USA
Blood 113:635-45. 2009..In conclusion, MALT subgroups with distinct pathologic features defined by distinct groups of deregulated genes were identified. These genes could represent novel diagnostic and therapeutic targets...
- Approach to the treatment of multiple myeloma: a clash of philosophiesS Vincent Rajkumar
Division of Hematology, Mayo Clinic, Rochester, MN, USA
Blood 118:3205-11. 2011....
- Long-term results of response to therapy, time to progression, and survival with lenalidomide plus dexamethasone in newly diagnosed myelomaMartha Q Lacy
Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
Mayo Clin Proc 82:1179-84. 2007..To determine the long-term effects of a combined regimen of lenalidomide and dexamethasone (Rev-Dex) on time to progression, progression-free survival, and overall survival (OS) in patients with multiple myeloma...
- Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myelomaJonathan J Keats
Comprehensive Cancer Center, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
Cancer Cell 12:131-44. 2007..These results highlight the critical importance of the NF-kappaB pathway in the pathogenesis of multiple myeloma...
- Multiple myeloma cells capacity to decompose H2O2 determines lenalidomide sensitivitySinto Sebastian
Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, AZ, United States
Blood . 2016..Our findings could help identify patients most likely to benefit from IMiDs and suggest direct TrxR or Trx inhibitors for MM therapy...
- Many multiple myelomas: making more of the molecular mayhemMarta Chesi
Department of Hematology, Mayo Clinic, Scottsdale, AZ 85259, USA
Hematology Am Soc Hematol Educ Program 2011:344-53. 2011..These patients should be enrolled in innovative clinical trials. The remaining patients with cyclin D translocations or hyperdiploidy do well with most therapies, and the goal should be to control disease while minimizing toxicity...
- Treatment of newly diagnosed multiple myeloma based on Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART): consensus statementAngela Dispenzieri
Division of Hematology, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905, USA
Mayo Clin Proc 82:323-41. 2007....
- Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myelomaMartha Q Lacy
Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
J Clin Oncol 27:5008-14. 2009..We report, to our knowledge, the first phase II trial of pomalidomide administered in combination with low-dose dexamethasone for the treatment of relapsed or refractory multiple myeloma...
- Molecular dissection of hyperdiploid multiple myeloma by gene expression profilingWee J Chng
Department of Hematology Oncology, Mayo Clinic, Scottsdale, Arizona, USA
Cancer Res 67:2982-9. 2007..Furthermore, the signatures that defined these clusters may provide a basis for tailoring treatment to individual patients...
- Genetics and cytogenetics of multiple myeloma: a workshop reportRafael Fonseca
Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
Cancer Res 64:1546-58. 2004..Areas in need of further study were identified. The study of the genetic aberrations will likely form the platform for targeted therapy for the disease...
- IAP antagonists induce anti-tumor immunity in multiple myelomaMarta Chesi
Department of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA
Nat Med 22:1411-1420. 2016..Notably, combination of LCL161 with the immune-checkpoint inhibitor anti-PD1 was curative in all of the treated mice...
- Phase Ib/II trial of CYKLONE (cyclophosphamide, carfilzomib, thalidomide and dexamethasone) for newly diagnosed myelomaJoseph R Mikhael
Mayo Clinic, Scottsdale, AZ, USA
Br J Haematol 169:219-27. 2015..Progression-free survival and overall survival at 24 months was 76% and 96%, respectively (median follow-up of 17·5 months). CYKLONE appears highly efficacious in NDMM patients, with manageable toxicities...
- Individualizing therapy using molecular markers in multiple myelomaP Leif Bergsagel
Mayo Clinic, 13400 E Shea Boulevard, Scottsdale, AZ 85259, USA
Clin Lymphoma Myeloma 7:S170-4. 2007..Stem cell transplantation is deferred in patients with high-risk molecular markers, and in all patients, response is followed closely and determines the individual timing and sequence of therapeutic regimens...
- UCHL1 is a biomarker of aggressive multiple myeloma required for disease progressionSajjad Hussain
Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA
Oncotarget 6:40704-18. 2015..We conclude that UCH-L1 is a biomarker of aggressive myeloma that may be an important marker of bortezomib response, and may itself be an effective target in disseminated disease. ..
- The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressorJotin Marango
Division of Hematology Oncology, Mount Sinai School of Medicine, New York, NY, USA
Blood 111:3145-54. 2008....
- Comprehensive identification of somatic mutations in chronic lymphocytic leukemiaP Leif Bergsagel
Comprehensive Cancer Center, Mayo Clinic Arizona, Scottsdale, USA
Cancer Cell 20:5-7. 2011..Early results for hematopoietic tumors show great promise, but many questions remain to be answered...
- Rearrangements and amplification of IER3 (IEX-1) represent a novel and recurrent molecular abnormality in myelodysplastic syndromesDavid P Steensma
Mayo Clinic, Rochester, MN 55905, USA
Cancer Res 69:7518-23. 2009..These data support involvement of IER3 in the pathobiology of MDS...
- Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and managementR A Kyle
Division of Hematology, Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA
Leukemia 24:1121-7. 2010..Testing should be done 2-3 months after the initial recognition of SMM. If the results are stable, the patient should be followed every 4-6 months for 1 year and, if stable, every 6-12 months...
- Multiple myeloma: evolving genetic events and host interactionsW Michael Kuehl
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda Naval Hospital, Maryland 20889 5105, USA
Nat Rev Cancer 2:175-87. 2002..What causes full-blown myeloma? And can our molecular understanding of this common haematological malignancy be used to develop effective preventive and treatment strategies?..
- Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomibGeorge Mulligan
Clinical Research Translational Medicine, Millennium Pharmaceuticals Inc, 40 Landsdowne Street, Cambridge, MA 02139, USA
Blood 109:3177-88. 2007..Informative gene expression data and genomic classifiers that predict clinical outcome can be derived from prospective clinical trials of new anticancer agents...
- The enigma of ectopic expression of FGFR3 in multiple myeloma: a critical initiating event or just a target for mutational activation during tumor progressionMarta Chesi
Weill Medical College of Cornell University, New York, USA
Curr Opin Hematol 9:288-93. 2002..However, it remains to be proven if and how dysregulation of FGFR3 or MMSET mediates an early oncogenic process in multiple myeloma...
- Chemotherapy of multiple myeloma: melphalan--40 years old and still going strongP Leif Bergsagel
Weill Medical College of Cornell University, New York, NY, USA
Biol Blood Marrow Transplant 9:2-3. 2003
- Critical roles for immunoglobulin translocations and cyclin D dysregulation in multiple myelomaP Leif Bergsagel
Weill Medical College of Cornell University, New York, NY 10021, USA
Immunol Rev 194:96-104. 2003..We speculate that ectopic cyclin D1 expression without t(11;14) is dependent on tumor-specific interaction with bone marrow stromal cells...
- Bone lesions in molecular subtypes of multiple myelomaDavide F Robbiani
N Engl J Med 351:197-8. 2004
- Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stromaElaine M Hurt
Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Cancer Cell 5:191-9. 2004..The frequent overexpression of c-maf in myeloma makes it an attractive target for therapeutic intervention...
- Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32)-positive multiple myeloma patientsJonathan J Keats
Department of Oncology, University of Alberta and Cross Cancer Institute, 11560 University Ave, Edmonton, AB, T6G 1Z2, Canada
Blood 105:4060-9. 2005..In contrast, RE-IIBP is universally dysregulated and also potentially functional in all t(4;14)POS patients irrespective of fibroblast growth factor receptor 3 (FGFR3) expression or breakpoint type...
- Advances in biology of multiple myeloma: clinical applicationsTeru Hideshima
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
Blood 104:607-18. 2004....
- Determinants of sensitivity to lovastatin-induced apoptosis in multiple myelomaW Wei Lynn Wong
Departments of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
Mol Cancer Ther 6:1886-97. 2007..003). These results suggest that statins may be a useful molecular targeted therapy in the treatment of a subset of MM...
- Inhibition of fibroblast growth factor receptor 3 induces differentiation and apoptosis in t(4;14) myelomaSuzanne Trudel
Department of Medicine, Weill Medical College and Graduate School of Medical Sciences, Cornell University, New York, NY 10021, USA
Blood 103:3521-8. 2004..In addition, this represents the validation of a therapeutic target in MM that may benefit patients who have a very poor prognosis with currently available treatments...
- Osteopontin dysregulation and lytic bone lesions in multiple myelomaDavide F Robbiani
Department of Medicine, Division of Hematology and Medical Oncology, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY, USA
Hematol Oncol 25:16-20. 2007..OPN is produced in osteolytic lesions: we propose that MM-derived OPN plays a critical role in bone disease by protecting bone from destruction...
- Prognostic factors in multiple myeloma: it's in the genesP Leif Bergsagel
Clin Cancer Res 9:533-4. 2003
- FGFR3 activates RSK2 to mediate hematopoietic transformation through tyrosine phosphorylation of RSK2 and activation of the MEK/ERK pathwaySumin Kang
Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
Cancer Cell 12:201-14. 2007..Our findings suggest that FGFR3 mediates hematopoietic transformation by activating RSK2 in a two-step fashion, promoting both the ERK-RSK2 interaction and subsequent phosphorylation of RSK2 by ERK...