Photo of Steven P. Treon,  MD, PhD

Steven P. Treon, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-2681
Fax: (617) 632-4862


steven_treon@dfci.harvard.edu

Steven P. Treon, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Associate Professor, Medicine, Harvard Medical School
  • Director, Bing Center for Waldenstrom's Macroglobulinemia, Adult Oncology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

The Bing Center cares for over 1,200 patients a year with WM, and IgM related disorders. Most patients seen in the Bing Center enter studies evaluating the genetic basis, pathogenesis and treatment of WM. A registry of patients and families funded through the International Waldenstrom’s Macroglobulinemia Foundation has recruited over 1000 patients and family members to study the genetic basis and predispositions for WM. The use of whole genome sequencing (WGS) has been used by us to define the genomic landscape of WM. Using paired normal/tumor tumor samples, we identified and validated highly recurring MYD88 (L265P) and CXCR4 WHIM-like somatic mutations. The discovery of MYD88 L265P somatic mutation which is present in 95% of WM patients has permitted the differentiation of WM from overlapping B-cell disorders, including marginal zone lymphoma and IgM myeloma. The feasibility for the diagnostic and response assessment potential for MYD88 L265P peripheral blood testing in WM was also demonstrated by my laboratory. In as well, my laboratory has worked on MYD88 L265P signaling in WM including and has shown the activation of IRAK 1/4/TRAF6/NFKB and defined for the first time signaling through Bruton’s tyrosine kinase (BTK). These findings led to a clinical trial in WM patients using the BTK inhibitor ibrutinib which has shown remarkable activity in relapsed/refractory WM patients, and led to the first breakthrough designation in oncology by the U.S. FDA, and subsequent approval of ibrutinib by the FDA and EMA for the treatment of WM. Our current efforts are now focused on defining the role of other recurring mutations in WM that are observed at lower frequencies, but which may still have important impact on pathogenesis and treatment (e.g. ARID1A, CD79A/B, and TP53), and gene loss in pathways that impact critical growth regulatory functions (e.g. HIVEP2, TNFAIP3). Transcriptomic and epigenomic analysis is also being undertaken, with the goal of developing a highly integrated genomic profile for MYD88 mutated and unmutated WM disease. My laboratory has also undertaken efforts to develop inhibitors of MYD88 signaling. Kinase inhibitors that target IRAK1 and HCK were developed as part of these efforts with Nathanael Gray’s group at Harvard Medical School, while a stapled peptide approach to disabling MYDDosome signaling is being pursued with Loren Walensky’s group at the Dana Farber Cancer Institute. The signaling pathway associated with the CXCR4 WHIM-like mutations which are present in 40% of WM patients has also been a focus of my laboratory. We showed that CXCR4-WHIM like mutations activate AKT and ERK, and block ibrutinib activity in vivo, and also associated with ibrutinib resistance in WM patients. Use of CXCR4 inhibitors in vitro block ibrutinib resistance, and a clinical trial with the CXCR4 inhibitor ulocuplomab is being initiated in WM. In addition to my clinical and laboratory activities, I also chair the Waldenstrom’s Macroglobulinemia Clinical Trials Group (WMCTG) and have conducted clinical studies focused on identifying novel agents for the primary and salvage therapy of WM. Many of the agents included in these trials were validated for their activity in WM by preclinical studies in my laboratory, and include monoclonal antibodies (rituximab, alemtuzumab), nucleoside analogue (fludarabine), bifunctional alkylator (bendamustine), immunomodulating agents (thalidomide, lenalidomide, pomalidomide), as well as proteasome (bortezomib, MLN4924, carfilzomib), phosphodiesterase (sildenafil), HMG-CoA reductase (simvastatin), c-kit (imatinib mesylate), MTOR (everolimus), BCR (ibrutinib, Avila 292) and BCL2 (ABT-199) inhibitors. These trials have resulted in the identification of many active treatments for WM patients, and identified specific risks in WM patients such as the rituximab-related IgM flare, disease transformation from nucleoside analogues, erythroid suppression by lenalidomide, late immune mediated thrombocytopenia by alemtuzumab, and IgM discordance by everolimus. These discoveries greatly impacted the standard of care for both primary and salvage therapy of WM, led to the first approval ever of an agent for the treatment of WM in the U.S. and Europe, and were incorporated into published International Consensus and National Comprehensive Cancer Network (NCCN) guidelines for WM patient management, as well as in many journal and textbook publications.

Publications

Powered by Harvard Catalyst
  • Castillo JJ, Garcia-Sanz R, Hatjiharissi E, Kyle RA, Leleu X, McMaster M, Merlini G, Minnema MC, Morra E, Owen RG, Poulain S, Stone MJ, Tam C, Varettoni M, Dimopoulos MA, Treon SP, Kastritis E. Recommendations for the diagnosis and initial evaluation of patients with Waldenström Macroglobulinaemia: A Task Force from the 8th International Workshop on Waldenström Macroglobulinaemia. British Journal of Haematology 2016. PubMed
  • Yang G, Buhrlage SJ, Tan L, Liu X, Chen J, Xu L, Tsakmaklis N, Chen JG, Patterson CJ, Brown JR, Castillo JJ, Zhang W, Zhang X, Liu S, Cohen P, Hunter ZR, Gray N, Treon SP. HCK is a survival determinant transactivated by mutated MYD88, and a direct target of ibrutinib. Blood 2016; 127:3237-52. PubMed
  • Hunter ZR, Xu L, Yang G, Tsakmaklis N, Vos JM, Liu X, Chen J, Manning RJ, Chen JG, Broadsky P, Patterson CJ, Gustine J, Debeau T, Castillo JJ, Anderson KC, Munshi NM, Treon SP. Next generation sequencing identifies a transcriptional profile that segues with genomic alterations in Waldenström macroglobulinemia. Blood 2016. PubMed
  • Cea M, Cagnetta A, Acharya C, Acharya P, Tai YT, Yang G, Lovera D, Soncini D, Miglino M, Fraternali-Orcioni G, Mastracci L, Nencioni A, Montecucco F, Monacelli F, Ballestrero A, Hideshima T, Chauhan D, Gobbi M, Lemoli RM, Munshi NC, Treon SP, Anderson KC. DUAL NAMPT AND BTK TARGETING LEADS TO SYNERGISTIC KILLING OF WALDENSTROM`S MACROGLOBULINEMIA CELLS REGARDLESS OF MYD88 AND CXCR4 SOMATIC MUTATIONS STATUS. Clin Cancer Res 2016. PubMed
  • Liu X, Hunter ZR, Xu L, Chen J, Chen JG, Tsakmaklis N, Patterson CJ, Castillo JJ, Buhrlage S, Gray N, Treon SP, Yang G. Targeting Myddosome Assembly in Waldenstrom Macroglobulinaemia. British Journal of Haematology 2016. PubMed
  • Anderson KC, Alsina M, Atanackovic D, Biermann JS, Chandler JC, Costello C, Djulbegovic B, Fung HC, Gasparetto C, Godby K, Hofmeister C, Holmberg L, Holstein S, Huff CA, Kassim A, Krishnan AY, Kumar SK, Liedtke M, Lunning M, Raje N, Reu FJ, Singhal S, Somlo G, Stockerl-Goldstein K, Treon SP, Weber D, Yahalom J, Shead DA, Kumar R. NCCN Guidelines Insights: Multiple Myeloma, Version 3.2016. J Natl Compr Canc Netw 2016; 14:389-400. PubMed
  • Gustine JN, Meid K, Dubeau TE, Treon SP, Castillo JJ. Atrial fibrillation associated with Ibrutinib in Waldenström's macroglobulinemia. Am J Hematol 2016. PubMed
  • Castillo JJ, Ghobrial IM, Treon SP. Response to ibrutinib in a patient with IgG lymphoplasmacytic lymphoma carrying the MYD88 L265P gene mutation. Leuk Lymphoma 2016. PubMed
  • Gustine J, Meid K, Xu L, Hunter ZR, Castillo JJ, Treon SP. To select or not to select? The role of B-cell selection in determining the MYD88 mutation status in Waldenström Macroglobulinaemia. British Journal of Haematology 2016. PubMed
  • Castillo JJ, D'Sa S, Lunn MP, Minnema MC, Tedeschi A, Lansigan F, Palomba ML, Varettoni M, Garcia-Sanz R, Nayak L, Lee EQ, Rinne ML, Norden AD, Ghobrial IM, Treon SP. Central nervous system involvement by Waldenström macroglobulinaemia (Bing-Neel syndrome): a multi-institutional retrospective study. British Journal of Haematology 2016; 172:709-15. PubMed
  • Roccaro AM, Sacco A, Shi J, Chiarini M, Perilla-Glen A, Manier S, Glavey S, Aljawai Y, Mishima Y, Kawano Y, Moschetta M, Correll M, Improgo MR, Brown JR, Imberti L, Rossi G, Castillo J, Treon SP, Freedman ML, Van Allen EM, Hide W, Hiller E, Rainville I, Ghobrial IM. Exome sequencing reveals recurrent germline variants in patients with familial Waldenstrom's macroglobulinemia. Blood 2016. PubMed
  • Xu L, Hunter ZR, Tsakmaklis N, Cao Y, Yang G, Chen J, Liu X, Kanan S, Castillo JJ, Tai YT, Zehnder JL, Brown JR, Carrasco RD, Advani R, Sabile JM, Argyropoulos K, Lia Palomba M, Morra E, Trojani A, Greco A, Tedeschi A, Varettoni M, Arcaini L, Munshi NM, Anderson KC, Treon SP. Clonal architecture of CXCR4 WHIM-like mutations in Waldenström Macroglobulinaemia. British Journal of Haematology 2015. PubMed
  • de Rooij MF, Kuil A, Kraan W, Kersten MJ, Treon SP, Pals ST, Spaargaren M. Ibrutinib and idelalisib target B cell receptor- but not CXCL12/CXCR4-controlled integrin-mediated adhesion in Waldenström macroglobulinemia. Haematologica 2015. PubMed
  • Nielsen JS, Sedgwick C, Shahid A, Zong Z, Brumme ZL, Yu S, Liu L, Kroeger DR, Treon SP, Connors JM, Gascoyne RD, Berry BR, Marra MA, Morin RD, Macpherson N, Nelson BH. Toward personalized lymphoma immunotherapy: Identification of common driver mutations recognized by patient CD8+ T cells. Clin Cancer Res 2015. PubMed
  • Castillo JJ, Kanan S, Meid K, Manning R, Hunter ZR, Treon SP. Rituximab intolerance in patients with Waldenström macroglobulinaemia. British Journal of Haematology 2015. PubMed
  • Anderson KC, Alsina M, Atanackovic D, Biermann JS, Chandler JC, Costello C, Djulbegovic B, Fung HC, Gasparetto C, Godby K, Hofmeister C, Holmberg L, Holstein S, Huff CA, Kassim A, Krishnan AY, Kumar SK, Liedtke M, Lunning M, Raje N, Singhal S, Smith C, Somlo G, Stockerl-Goldstein K, Treon SP, Weber D, Yahalom J, Shead DA, Kumar R. Multiple Myeloma, Version 2.2016. J Natl Compr Canc Netw 2015; 13:1398-435. PubMed
  • Treon SP, Xu L, Hunter Z. MYD88 Mutations and Response to Ibrutinib in Waldenström's Macroglobulinemia. N Engl J Med 2015; 373:584-6. PubMed
  • Treon SP. How I treat Waldenström macroglobulinemia. Blood 2015. PubMed
  • Castillo JJ, Olszewski AJ, Kanan S, Meid K, Hunter ZR, Treon SP. Survival outcomes of secondary cancers in patients with Waldenström macroglobulinemia: An analysis of the SEER database. Am J Hematol 2015. PubMed
  • Cao Y, Yang G, Hunter ZR, Liu X, Xu L, Chen J, Tsakmaklis N, Hatjiharissi E, Kanan S, Davids MS, Castillo JJ, Treon SP. The BCL2 antagonist ABT-199 triggers apoptosis, and augments ibrutinib and idelalisib mediated cytotoxicity in CXCR4 Wild-type and CXCR4 WHIM mutated Waldenstrom macroglobulinaemia cells. British Journal of Haematology 2015. PubMed
  • Kuiatse I, Baladandayuthapani V, Lin HY, Thomas SK, Bjorklund CC, Weber DM, Wang M, Shah JJ, Zhang XD, Jones RJ, Ansell SM, Yang G, Treon SP, Orlowski RZ. Targeting the Spleen Tyrosine Kinase with Fostamatinib as a Strategy against Waldenström Macroglobulinemia. Clin Cancer Res 2015. PubMed
  • Zhu D, Wang Z, Zhao JJ, Calimeri T, Meng J, Hideshima T, Fulciniti M, Kang Y, Ficarro SB, Tai YT, Hunter Z, McMilin D, Tong H, Mitsiades CS, Wu CJ, Treon SP, Dorfman DM, Pinkus G, Munshi NC, Tassone P, Marto JA, Anderson KC, Carrasco RD. The Cyclophilin A-CD147 complex promotes the proliferation and homing of multiple myeloma cells. Nat Med 2015; 21:572-80. PubMed
  • Leblebjian H, Noonan K, Paba-Prada C, Treon SP, Castillo JJ, Ghobrial IM. Cyclophosphamide, bortezomib, and dexamethasone combination in waldenstrom macroglobulinemia. Am J Hematol 2015. PubMed
  • Treon SP, Tripsas CK, Meid K, Warren D, Varma G, Green R, Argyropoulos KV, Yang G, Cao Y, Xu L, Patterson CJ, Rodig S, Zehnder JL, Aster JC, Harris NL, Kanan S, Ghobrial I, Castillo JJ, Laubach JP, Hunter ZR, Salman Z, Li J, Cheng M, Clow F, Graef T, Palomba ML, Advani RH. Ibrutinib in previously treated Waldenström's macroglobulinemia. N Engl J Med 2015; 372:1430-40. PubMed
  • Castillo JJ, Olszewski AJ, Kanan S, Meid K, Hunter ZR, Treon SP. Overall survival and competing risks of death in patients with Waldenström macroglobulinaemia: an analysis of the Surveillance, Epidemiology and End Results database. British Journal of Haematology 2015; 169:81-9. PubMed
  • Castillo JJ, Olszewski AJ, Hunter ZR, Kanan S, Meid K, Treon SP. Incidence of secondary malignancies among patients with Waldenström macroglobulinemia: An analysis of the SEER database. Cancer 2015. PubMed
  • Cao Y, Hunter ZR, Liu X, Xu L, Yang G, Chen J, Tsakmaklis N, Kanan S, Castillo JJ, Treon SP. CXCR4 WHIM-like frameshift and nonsense mutations promote ibrutinib resistance but do not supplant MYD88(L265P) -directed survival signalling in Waldenström macroglobulinaemia cells. British Journal of Haematology 2015; 168:701-7. PubMed
  • Banwait R, Aljawai Y, Cappuccio J, McDiarmid S, Morgan EA, Leblebjian H, Roccaro AM, Laubach J, Castillo JJ, Paba-Prada C, Treon S, Redd R, Weller E, Ghobrial IM. Extramedullary Waldenström macroglobulinemia. Am J Hematol 2015; 90:100-4. PubMed
  • Castillo JJ, Ghobrial IM, Treon SP. Biology, prognosis, and therapy of Waldenström Macroglobulinemia. Cancer Treat Res 2015; 165:177-95. PubMed
  • Treon SP, Hunter ZR, Castillo JJ, Merlini G. Waldenström macroglobulinemia. Hematol Oncol Clin North Am 2014; 28:945-70. PubMed
  • Zhou Y, Liu X, Xu L, Hunter ZR, Cao Y, Yang G, Carrasco R, Treon SP. Transcriptional repression of plasma cell differentiation is orchestrated by aberrant over-expression of the ETS factor SPIB in Waldenström macroglobulinaemia. British Journal of Haematology 2014. PubMed
  • Dimopoulos MA, Kastritis E, Owen RG, Kyle RA, Landgren O, Morra E, Leleu X, García-Sanz R, Munshi N, Anderson KC, Terpos E, Ghobrial IM, Morel P, Maloney D, Rummel M, Leblond V, Advani RH, Gertz MA, Kyriakou C, Thomas SK, Barlogie B, Gregory SA, Kimby E, Merlini G, Treon SP. Treatment recommendations for patients with Waldenström macroglobulinemia (WM) and related disorders: IWWM-7 consensus. Blood 2014; 124:1404-11. PubMed
  • Treon SP, Tripsas CK, Meid K, Kanan S, Sheehy P, Chuma S, Xu L, Cao Y, Yang G, Liu X, Patterson CJ, Warren D, Hunter ZR, Turnbull B, Ghobrial IM, Castillo JJ. Carfilzomib, rituximab, and dexamethasone (CaRD) treatment offers a neuropathy-sparing approach for treating Waldenström's macroglobulinemia. Blood 2014. PubMed
  • Castillo JJ, Olszewski AJ, Cronin AM, Hunter ZR, Treon SP. Survival trends in Waldenström macroglobulinemia: an analysis of the Surveillance, Epidemiology and End Results database. Blood 2014; 123:3999-4000. PubMed
  • Wu H, Wang W, Liu F, Weisberg EL, Tian B, Chen Y, Li B, Wang A, Wang B, Zhao Z, McMillin DW, Hu C, Li H, Wang J, Liang Y, Buhrlage SJ, Liang J, Liu J, Yang G, Brown JR, Treon SP, Mitsiades CS, Griffin JD, Liu Q, Gray NS. Discovery of a potent, covalent BTK inhibitor for B-cell lymphoma. ACS Chem Biol 2014. PubMed
  • Treon SP, Cao Y, Xu L, Yang G, Liu X, Hunter ZR. Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstrom macroglobulinemia. Blood 2014. PubMed
  • Fulciniti M, Amodio N, Bandi RL, Munshi M, Yang G, Xu L, Hunter Z, Tassone P, Anderson KC, Treon SP, Munshi NC. MYD88-independent growth and survival effects of Sp1 transactivation in Waldenstrom macroglobulinemia. Blood 2014; 123:2673-81. PubMed
  • Zhao JJ, Lin J, Zhu D, Wang X, Brooks D, Chen M, Chu ZB, Takada K, Ciccarelli B, Admin S, Tao J, Tai YT, Treon S, Pinkus G, Kuo WP, Hideshima T, Bouxsein M, Munshi N, Anderson K, Carrasco R. miR-30-5p functions as a tumor suppressor and novel therapeutic tool by targeting the oncogenic Wnt/β-catenin/BCL9 pathway. Cancer Res 2014; 74:1801-13. PubMed
  • Hunter ZR, Xu L, Yang G, Zhou Y, Liu X, Cao Y, Manning RJ, Tripsas C, Patterson CJ, Sheehy P, Treon SP. The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood 2014; 123:1637-46. PubMed
  • Ghobrial IM, Witzig TE, Gertz M, LaPlant B, Hayman S, Camoriano J, Lacy M, Bergsagel PL, Chuma S, DeAngelo D, Treon SP. Long-term results of the phase II trial of the oral mTOR inhibitor everolimus (RAD001) in relapsed or refractory Waldenstrom Macroglobulinemia. Am J Hematol 2014; 89:237-42. PubMed
  • Sahin I, Leblebjian H, Treon SP, Ghobrial IM. Waldenström macroglobulinemia: from biology to treatment. Expert Rev Hematol 2014; 7:157-68. PubMed
  • Treon SP. Proteasome inhibitors in Waldenström macroglobulinemia. Blood 2013; 122:3243-4. PubMed
  • Yang G, Zhou Y, Liu X, Xu L, Cao Y, Manning RJ, Patterson CJ, Buhrlage SJ, Gray N, Tai YT, Anderson KC, Hunter ZR, Treon SP. A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia. Blood 2013; 122:1222-32. PubMed
  • Sacco A, Zhang Y, Maiso P, Manier S, Rossi G, Treon SP, Ghobrial IM, Roccaro AM. microRNA aberrations in Waldenström macroglobulinemia. Clin Lymphoma Myeloma Leuk 2013. PubMed
  • Treon SP, Tripsas CK, Ciccarelli BT, Manning RJ, Patterson CJ, Sheehy P, Hunter ZR. Patients with Waldenström macroglobulinemia commonly present with iron deficiency and those with severely depressed transferrin saturation levels show response to parenteral iron administration. Clin Lymphoma Myeloma Leuk 2013. PubMed
  • Xu L, Hunter ZR, Yang G, Zhou Y, Cao Y, Liu X, Morra E, Trojani A, Greco A, Arcaini L, Varettoni M, Varettoni M, Brown JR, Tai YT, Anderson KC, Munshi NC, Patterson CJ, Manning RJ, Tripsas CK, Lindeman NI, Treon SP. MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction. Blood 2013; 121:2051-8. PubMed
  • Owen RG, Kyle RA, Stone MJ, Rawstron AC, Leblond V, Merlini G, Garcia-Sanz R, Ocio EM, Morra E, Morel P, Anderson KC, Patterson CJ, Munshi NC, Tedeschi A, Joshua DE, Kastritis E, Terpos E, Ghobrial IM, Leleu X, Gertz MA, Ansell SM, Morice WG, Kimby E, Treon SP, . Response assessment in Waldenström macroglobulinaemia: update from the VIth International Workshop. British Journal of Haematology 2013. PubMed
  • Anderson KC, Alsina M, Bensinger W, Biermann JS, Cohen AD, Devine S, Djulbegovic B, Faber EA, Gasparetto C, Hernandez-Illizaliturri F, Huff CA, Kassim A, Krishnan AY, Liedtke M, Meredith R, Raje N, Schriber J, Singhal S, Somlo G, Stockerl-Goldstein K, Treon SP, Weber D, Yahalom J, Yunus F, Shead DA, Kumar R. Multiple myeloma, version 1.2013. J Natl Compr Canc Netw 2013; 11:11-7. PubMed
  • Treon SP, Tripsas C, Hanzis C, Ioakimidis L, Patterson CJ, Manning RJ, Sheehy P, Turnbull B, Hunter ZR. Familial disease predisposition impacts treatment outcome in patients with Waldenström macroglobulinemia. Clin Lymphoma Myeloma Leuk 2012; 12:433-7. PubMed
  • Anderson KC, Alsina M, Bensinger W, Biermann JS, Cohen AD, Devine S, Djulbegovic B, Faber EA, Gasparetto C, Hernandez-Ilizaliturri F, Huff CA, Kassim A, Krishnan AY, Medeiros BC, Meredith R, Raje N, Schriber J, Singhal S, Somlo G, Stockerl-Goldstein K, Treon SP, Tricot G, Weber DM, Yahalom J, Yunus F, Kumar R, Shead DA, . Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma, version 2.2013. J Natl Compr Canc Netw 2012; 10:1211-9. PubMed
  • Treon SP, Xu L, Yang G, Zhou Y, Liu X, Cao Y, Sheehy P, Manning RJ, Patterson CJ, Tripsas C, Arcaini L, Pinkus GS, Rodig SJ, Sohani AR, Harris NL, Laramie JM, Skifter DA, Lincoln SE, Hunter ZR. MYD88 L265P somatic mutation in Waldenström's macroglobulinemia. N Engl J Med 2012; 367:826-33. PubMed
  • Tai YT, Chang BY, Kong SY, Fulciniti M, Yang G, Calle Y, Hu Y, Lin J, Zhao JJ, Cagnetta A, Cea M, Sellitto MA, Zhong MY, Wang Q, Acharya C, Carrasco DR, Buggy JJ, Elias L, Treon SP, Matsui W, Richardson P, Munshi NC, Anderson KC. Bruton tyrosine kinase inhibition is a novel therapeutic strategy targeting tumor in the bone marrow microenvironment in multiple myeloma. Blood 2012; 120:1877-87. PubMed
  • Grass S, Preuss KD, Wikowicz A, Terpos E, Ziepert M, Nikolaus D, Yang Y, Fadle N, Regitz E, Dimopoulos MA, Treon SP, Hunter ZR, Pfreundschuh M. Hyperphosphorylated paratarg-7: a new molecularly defined risk factor for monoclonal gammopathy of undetermined significance of the IgM type and Waldenstrom macroglobulinemia. Blood 2011; 117:2918-23. PubMed
  • Treon SP, Merlini G, Morra E, Patterson CJ, Stone MJ. Report from the Sixth International Workshop on Waldenström's Macroglobulinemia. Clin Lymphoma Myeloma Leuk 2011; 11:68-73. PubMed
  • Ciccarelli BT, Patterson CJ, Hunter ZR, Hanzis C, Ioakimidis L, Manning R, Yang G, Xu L, Zhou Y, Sun J, Liu X, Tseng H, Cao Y, Sheehy P, Rodig SJ, Treon SP. Hepcidin is produced by lymphoplasmacytic cells and is associated with anemia in Waldenström's macroglobulinemia. Clin Lymphoma Myeloma Leuk 2011; 11:160-3. PubMed
  • Sun JY, Xu L, Tseng H, Ciccarelli B, Fulciniti M, Hunter ZR, Maghsoudi K, Hatjiharissi E, Zhou Y, Yang G, Zhu B, Liu X, Gong P, Ioakimidis L, Sheehy P, Patterson CJ, Munshi NC, O'Connor OA, Treon SP. Histone deacetylase inhibitors demonstrate significant preclinical activity as single agents, and in combination with bortezomib in Waldenström's macroglobulinemia. Clin Lymphoma Myeloma Leuk 2011; 11:152-6. PubMed
  • Treon SP, Hanzis C, Tripsas C, Ioakimidis L, Patterson CJ, Manning RJ, Sheehy P. Bendamustine therapy in patients with relapsed or refractory Waldenström's macroglobulinemia. Clin Lymphoma Myeloma Leuk 2011; 11:133-5. PubMed
  • Hanzis C, Ojha RP, Hunter Z, Manning R, Lewicki M, Brodsky P, Ioakimidis L, Tripsas C, Patterson CJ, Sheehy P, Treon SP. Associated malignancies in patients with Waldenström's macroglobulinemia and their kin. Clin Lymphoma Myeloma Leuk 2011; 11:88-92. PubMed
  • Treon SP. Fc粒 receptor predictive genomic testing and the treatment of indolent non-Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk 2010; 10:321-2. PubMed
  • Ghobrial IM, Xie W, Padmanabhan S, Badros A, Rourke M, Leduc R, Chuma S, Kunsman J, Warren D, Poon T, Harris B, Sam A, Anderson KC, Richardson PG, Treon SP, Weller E, Matous J. Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenstr旦m Macroglobulinemia. Am J Hematol 2010; 85:670-4. PubMed
  • Prabhala RH, Pelluru D, Fulciniti M, Prabhala HK, Nanjappa P, Song W, Pai C, Amin S, Tai YT, Richardson PG, Ghobrial IM, Treon SP, Daley JF, Anderson KC, Kutok JL, Munshi NC. Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma. Blood 2010; 115:5385-92. PubMed
  • Dimopoulos MA, Chen C, Kastritis E, Gavriatopoulou M, Treon SP. Bortezomib as a treatment option in patients with Waldenstr旦m macroglobulinemia. Clin Lymphoma Myeloma Leuk 2010; 10:110-7. PubMed
  • Ghobrial IM, Hong F, Padmanabhan S, Badros A, Rourke M, Leduc R, Chuma S, Kunsman J, Warren D, Harris B, Sam A, Anderson KC, Richardson PG, Treon SP, Weller E, Matous J. Phase II trial of weekly bortezomib in combination with rituximab in relapsed or relapsed and refractory Waldenstrom macroglobulinemia. J Clin Oncol 2010; 28:1422-8. PubMed
  • Ghobrial IM, Gertz M, Laplant B, Camoriano J, Hayman S, Lacy M, Chuma S, Harris B, Leduc R, Rourke M, Ansell SM, Deangelo D, Dispenzieri A, Bergsagel L, Reeder C, Anderson KC, Richardson PG, Treon SP, Witzig TE. Phase II trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory Waldenstrom macroglobulinemia. J Clin Oncol 2010; 28:1408-14. PubMed
  • Hunter ZR, Manning RJ, Hanzis C, Ciccarelli BT, Ioakimidis L, Patterson CJ, Lewicki MC, Tseng H, Gong P, Liu X, Zhou Y, Yang G, Sun J, Xu L, Sheehy P, Morra M, Treon SP. IgA and IgG hypogammaglobulinemia in Waldenstr旦m's macroglobulinemia. Haematologica 2010; 95:470-5. PubMed
  • Fonseca R, Richardson P, Giralt S, Lonial S, Rajkumar SV, Stewart AK, Bensinger W, Somlo G, Vescio R, Mikhael J, Reeder C, Tiedemann R, Tricot G, Rifkin R, Shaughnessy J, Munshi N, Raje N, Ghobrial I, Laubach J, Schlossman R, Treon S, Mahindra A, Avigan D, Rosenblatt J, Jagannath S, Niesvizky R, Landau H, Chen-Kiang S, Siegel DS, Zimmerman T, Mehta J, Vesole D, Rosen S, Hofmeister C, Lacy M, Dispenzieri A, Borrello I, Hayman SR, Kumar S, Buadi F, Dingli D, Russell S, Melissa Alsina MA, Fernandez H, Roy V, Pereira D, Stadtmauer E, Vij R, Jakubowiak A, Lentzsch S, Song K, Trudel S, Chen C, Reece D, Stewart D, Singhal S, Comenzo R, Gertz MA, Greipp PR, Durie B, Barlogie B, Anderson K, Dalton W, Coleman M, Novis S, Kyle RA. Conflicts of interest, authorship, and disclosures in industry-related scientific publications. Mayo Clin Proc 2010; 85:197-9; author reply 201-4. PubMed
  • Treon SP. How I treat Waldenstr旦m macroglobulinemia. Blood 2009; 114:2375-85. PubMed
  • Treon SP, Ioakimidis L, Soumerai JD, Patterson CJ, Sheehy P, Nelson M, Willen M, Matous J, Mattern J, Diener JG, Keogh GP, Myers TJ, Boral A, Birner A, Esseltine DL, Ghobrial IM. Primary therapy of Waldenstr旦m macroglobulinemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180. J Clin Oncol 2009; 27:3830-5. PubMed
  • Morel P,Duhamel A,Gobbi P,Dimopoulos MA,Dhodapkar MV,McCoy J,Crowley J,Ocio EM,Garcia-Sanz R,Treon SP,Leblond V,Kyle RA,Barlogie B,Merlini G. International prognostic scoring system for Waldenstrom macroglobulinemia. Blood 2009; 113:4163-70. PubMed
  • Treon SP,Branagan AR,Ioakimidis L,Soumerai JD,Patterson CJ,Turnbull B,Wasi P,Emmanouilides C,Frankel SR,Lister A,Morel P,Matous J,Gregory SA,Kimby E. Long-term outcomes to fludarabine and rituximab in Waldenstrom macroglobulinemia. Blood 2008; 113:3673-8. PubMed
  • Leleu X,Hunter ZR,Xu L,Roccaro AM,Moreau AS,Santos DD,Hatjiharissi E,Bakthavachalam V,Adamia S,Ho AW,Soumerai J,Patterson CJ,Manning RJ,Hamilton S,Verselis S,Fox E,Carrasco R,Ghobrial IM,Treon SP. Expression of regulatory genes for lymphoplasmacytic cell differentiation in Waldenstrom Macroglobulinemia. British Journal of Haematology 2009; 145:59-63. PubMed
  • Treon SP,Patterson CJ,Kimby E,Stone MJ. Advances in the biology and treatment of Waldenstrom's macroglobulinemia: a report from the 5th International Workshop on Waldenstrom's Macroglobulinemia, Stockholm, Sweden. Clin Lymphoma Myeloma 2009; 9:10-5. PubMed
  • Ciccarelli BT,Yang G,Hatjiharissi E,Ioakimidis L,Patterson CJ,Manning RJ,Xu L,Liu X,Tseng H,Gong P,Sun J,Zhou Y,Treon SP. Soluble CD27 is a faithful marker of disease burden and is unaffected by the rituximab-induced IgM flare, as well as by plasmapheresis, in patients with Waldenstrom's macroglobulinemia. Clin Lymphoma Myeloma 2009; 9:56-8. PubMed
  • Ioakimidis L,Patterson CJ,Hunter ZR,Soumerai JD,Manning RJ,Turnbull B,Sheehy P,Treon SP. Comparative outcomes following CP-R, CVP-R, and CHOP-R in Waldenstrom's macroglobulinemia. Clin Lymphoma Myeloma 2009; 9:62-6. PubMed
  • Menke MN,Feke GT,McMeel JW,Treon SP. Ophthalmologic techniques to assess the severity of hyperviscosity syndrome and the effect of plasmapheresis in patients with Waldenstrom's macroglobulinemia. Clin Lymphoma Myeloma 2009; 9:100-3. PubMed
  • Leleu X,Tamburini J,Roccaro A,Morel P,Soumerai J,Levy V,Wemeau M,Balkaran S,Poulain S,Hunter ZR,Ghobrial IM,Treon SP,Leblond V. Balancing risk versus benefit in the treatment of Waldenstrom's Macroglobulinemia patients with nucleoside analogue-based therapy. Clin Lymphoma Myeloma 2009; 9:71-3. PubMed
  • Leleu X,Xu L,Jia X,Sacco A,Farag M,Hunter ZR,Moreau AS,Ngo HT,Hatjiharissi E,Ho AW,Santos DD,Adamia S,O'Connor K,Ciccarelli B,Soumerai J,Manning RJ,Patterson CJ,Roccaro AM,Ghobrial IM,Treon SP. Endoplasmic reticulum stress is a target for therapy in Waldenstrom macroglobulinemia. Blood 2008; 113:626-34. PubMed
  • Leleu X,Soumerai J,Roccaro A,Hatjiharissi E,Hunter ZR,Manning R,Ciccarelli BT,Sacco A,Ioakimidis L,Adamia S,Moreau AS,Patterson CJ,Ghobrial IM,Treon SP. Increased incidence of transformation and myelodysplasia/acute leukemia in patients with Waldenstrom macroglobulinemia treated with nucleoside analogs. J Clin Oncol 2008; 27:250-5. PubMed
  • Treon SP,Soumerai JD,Branagan AR,Hunter ZR,Patterson CJ,Ioakimidis L,Chu L,Musto P,Baron AD,Nunnink JC,Kash JJ,Terjanian TO,Hyman PM,Nawfel EL,Sharon DJ,Munshi NC,Anderson KC. Lenalidomide and rituximab in Waldenstrom's macroglobulinemia. Clin Cancer Res 2009; 15:355-60. PubMed
  • Dimopoulos MA,Gertz MA,Kastritis E,Garcia-Sanz R,Kimby EK,Leblond V,Fermand JP,Merlini G,Morel P,Morra E,Ocio EM,Owen R,Ghobrial IM,Seymour J,Kyle RA,Treon SP. Update on treatment recommendations from the Fourth International Workshop on Waldenstrom's Macroglobulinemia. J Clin Oncol 2008; 27:120-6. PubMed
  • Adamia S,Reichert AA,Kuppusamy H,Kriangkum J,Ghosh A,Hodges JJ,Pilarski PM,Treon SP,Mant MJ,Reiman T,Belch AR,Pilarski LM. Inherited and acquired variations in the hyaluronan synthase 1 (HAS1) gene may contribute to disease progression in multiple myeloma and Waldenstrom macroglobulinemia. Blood 2008; 112:5111-21. PubMed
  • Treon SP,Soumerai JD,Branagan AR,Hunter ZR,Patterson CJ,Ioakimidis L,Briccetti FM,Pasmantier M,Zimbler H,Cooper RB,Moore M,Hill J 2nd,Rauch A,Garbo L,Chu L,Chua C,Nantel SH,Lovett DR,Boedeker H,Sonneborn H,Howard J,Musto P,Ciccarelli BT,Hatjiharissi E,Anderson KC. Thalidomide and rituximab in Waldenstrom macroglobulinemia. Blood 2008; 112:4452-7. PubMed
  • Ho AW, Hatjiharissi E, Ciccarelli BT, Branagan AR, Hunter ZR, Leleu X, Tournilhac O, Xu L, O'Connor K, Manning RJ, Santos DD, Chemaly M, Patterson CJ, Soumerai JD, Munshi NC, McEarchern JA, Law CL, Grewal IS, Treon SP. CD27-CD70 interactions in the pathogenesis of Waldenstrom's Macroglobulinemia. Blood 2008; 112:4683-9. PubMed
  • Moreau AS,Jia X,Patterson CJ,Roccaro AM,Xu L,Sacco A,O'Connor K,Soumerai J,Ngo HT,Hatjiharissi E,Hunter ZR,Ciccarelli B,Manning R,Ghobrial IM,Leleu X,Treon SP. The HMG-CoA inhibitor, simvastatin, triggers in vitro anti-tumour effect and decreases IgM secretion in Waldenstrom macroglobulinaemia. British Journal of Haematology 2008; 142:775-85. PubMed
  • Moreau AS, Sebti Y, Duhamel A, Roccaro AM, Coiteux V, Gastinne T, Friec GL, Burwick N, Amiot L, Ho AW, Poulain S, Hennache B, Hunter ZR, Dessaint JP, Ghobrial IM, Treon SP, Facon T, Zorn E, Leleu X. Clinical relevance of soluble HLA class I molecules in Waldenstrom Macroglobulinemia. Eur J Haematol 2008; 80:503-9. PubMed
  • Leleu X, Eeckhoute J, Jia X, Roccaro AM, Moreau AS, Farag M, Sacco A, Ngo HT, Runnels J, Melham MR, Burwick N, Azab A, Azab F, Hunter Z, Hatjiharissi E, Carrasco DR, Treon SP, Witzig TE, Hideshima T, Brown M, Anderson KC, Ghobrial IM. Targeting NF-{kappa}B in Waldenstrom macroglobulinemia. Blood 2008; 111:5068-77. PubMed
  • Leleu X, Moreau AS, Weller E, Roccaro AM, Coiteux V, Manning R, Nelson M, Leduc R, Robu D, Dupire S, Hatjiharissi E, Burwick N, Darre S, Hennache B, Treon SP, Facon T, Gertz MA, Ghobrial IM. Serum immunoglobulin free light chain correlates with tumor burden markers in Waldenstrom macroglobulinemia. Leuk Lymphoma 2008. PubMed
  • Roccaro AM, Leleu X, Sacco A, Moreau AS, Hatjiharissi E, Jia X, Xu L, Ciccarelli B, Patterson CJ, Ngo HT, Russo D, Vacca A, Dammacco F, Anderson KC, Ghobrial IM, Treon SP. Resveratrol exerts antiproliferative activity and induces apoptosis in Waldenstrom's macroglobulinemia. Clin Cancer Res 2008; 14:1849-58. PubMed
  • Treon SP, Hatjiharissi E, Merlini G. Waldenstrom's macrogloblinemia/ lymphoplasmacytic lymphoma. Cancer Treat Res 2008; 142:211-42. PubMed
  • Leleu X, Jia X, Runnels J, Ngo HT, Moreau AS, Farag M, Spencer JA, Pitsillides CM, Hatjiharissi E, Roccaro A, O'Sullivan G, McMillin DW, Moreno D, Kiziltepe T, Carrasco R, Treon SP, Hideshima T, Anderson KC, Lin CP, Ghobrial IM. The Akt pathway regulates survival and homing in Waldenstrom macroglobulinemia. Blood 2007; 110:4417-26. PubMed
  • Hatjiharissi E, Xu L, Santos DD, Hunter ZR, Ciccarelli BT, Verselis S, Modica M, Cao Y, Manning RJ, Leleu X, Dimmock EA, Kortsaris A, Mitsiades C, Anderson KC, Fox EA, Treon SP. Increased natural killer cell expression of CD16, and augmented binding and ADCC activity to rituximab among individuals expressing the Fc{gamma}RIIIA-158 V/V and V/F polymorphism. Blood 2007; 110:2561-4. PubMed
  • Ditzel Santos D, Ho AW, Tournilhac O, Hatjiharissi E, Leleu X, Xu L, Tassone P, Neri P, Hunter ZR, Chemaly MA, Branagan AR, Manning RJ, Patterson CJ, Moreau AS, Ciccarelli B, Adamia S, Kriangkum J, Kutok JL, Tai YT, Zhang J, Pilarski LM, Anderson KC, Munshi N, Treon SP. Establishment of BCWM.1 cell line for Waldenstrom's macroglobulinemia with productive in vivo engraftment in SCID-hu mice. Exp Hematol 2007; 35:1366-75. PubMed
  • Treon SP, Hatjiharissi E, Leleu X, Moreau AS, Roccaro A, Hunter ZR, Soumerai JD, Ciccarelli B, Xu L, Sacco A, Ngo HT, Jia X, Yang C, Adamia S, Branagan AR, Ho AW, Santos DD, Tournilhac O, Manning RJ, Leduc R, O'Connor K, Nelson M, Patterson CJ, Ghobrial I. Novel agents in the treatment of Waldenstrom's macroglobulinemia. Clin Lymphoma Myeloma 2007; 7 Suppl 5:S199-206. PubMed
  • Treon SP, Hunter ZR, Matous J, Joyce RM, Mannion B, Advani R, Cook D, Songer J, Hill J, Kaden BR, Sharon D, Steiss R, Leleu X, Branagan AR, Badros A. Multicenter Clinical Trial of Bortezomib in Relapsed/Refractory Waldenstrom's Macroglobulinemia: Results of WMCTG Trial 03-248. Clin Cancer Res 2007; 13:3320-5. PubMed
  • Moreau AS, Jia X, Ngo HT, Leleu X, O'sullivan G, Alsayed Y, Leontovich A, Podar K, Kutok J, Daley J, Lazo-Kallanian S, Hatjiharissi E, Raab MS, Xu L, Treon SP, Hideshima T, Anderson KC, Ghobrial IM. Protein kinase C inhibitor enzastaurin induces in vitro and in vivo antitumor activity in Waldenstrom macroglobulinemia. Blood 2007; 109:4964-72. PubMed
  • Hatjiharissi E, Ngo H, Leontovich AA, Leleu X, Timm M, Melhem M, George D, Lu G, Ghobrial J, Alsayed Y, Zeismer S, Cabanela M, Nehme A, Jia X, Moreau AS, Treon SP, Fonseca R, Gertz MA, Anderson KC, Witzig TE, Ghobrial IM. Proteomic analysis of waldenstrom macroglobulinemia. Cancer Res 2007; 67:3777-84. PubMed
  • Rodig SJ, Abramson JS, Pinkus GS, Treon SP, Dorfman DM, Dong HY, Shipp MA, Kutok JL. Heterogeneous CD52 expression among hematologic neoplasms: implications for the use of alemtuzumab (CAMPATH-1H). Clin Cancer Res 2006; 12:7174-9. PubMed
  • Shammas MA, Neri P, Koley H, Batchu RB, Bertheau RC, Munshi V, Prabhala R, Fulciniti M, Tai YT, Treon SP, Goyal RK, Anderson KC, Munshi NC. Specific killing of multiple myeloma cells by (-)- epigallocatechin-3-gallate extracted from green tea: biological activity and therapeutic implications. Blood 2006; 108:2804-10. PubMed
  • Tournilhac O, Santos DD, Xu L, Kutok J, Tai YT, Le Gouill S, Catley L, Hunter Z, Branagan AR, Boyce JA, Munshi N, Anderson KC, Treon SP. Mast cells in Waldenstrom's macroglobulinemia support lymphoplasmacytic cell growth through CD154/CD40 signaling. Ann Oncol 2006; 17:1275-82. PubMed
  • Mitsiades CS, Mitsiades NS, Munshi NC, Richardson PG, Anderson KC. The role of the bone microenvironment in the pathophysiology and therapeutic management of multiple myeloma: Interplay of growth factors, their receptors and stromal interactions. Eur J Cancer 2006; 42:1564-73. PubMed
  • Santos DD, Hatjiharissi E, Tournilhac O, Chemaly MZ, Leleu X, Xu L, Patterson C, Branagan AR, Manning RJ, Ho AW, Hunter ZR, Dimmock EA, Kutok JL, Churchill WH, Castells MC, Tai YT, Anderson KC, Treon SP. CD52 is expressed on human mast cells and is a potential therapeutic target in Waldenstrom's Macroglobulinemia and mast cell disorders. Clin Lymphoma Myeloma 2006; 6:478-83. PubMed
  • Tassone P, Neri P, Kutok JL, Tournilhac O, Santos DD, Hatjiharissi E, Munshi V, Venuta S, Anderson KC, Treon SP, Munshi NC. A SCID-hu in vivo model of human Waldenstr旦m macroglobulinemia. Blood 2005; 106:1341-5. PubMed
  • Adamia S, Treon SP, Reiman T, Tournilhac O, McQuarrie C, Mant MJ, Belch AR, Pilarski LM. Potential impact of a single nucleotide polymorphism in the hyaluronan synthase 1 gene in Waldenstrom's macroglobulinemia. Clin Lymphoma 2005; 5:253-6. PubMed
  • Tai YT, Catley LP, Mitsiades CS, Burger R, Podar K, Shringpaure R, Hideshima T, Chauhan D, Hamasaki M, Ishitsuka K, Richardson P, Treon SP, Munshi NC, Anderson KC. Mechanisms by which SGN-40, a humanized anti-CD40 antibody, induces cytotoxicity in human multiple myeloma cells: clinical implications. Cancer Res 2004; 64:2846-52. PubMed
  • Tai YT, Podar K, Mitsiades N, Lin B, Mitsiades C, Gupta D, Akiyama M, Catley L, Hideshima T, Munshi NC, Treon SP, Anderson KC. CD40 induces human multiple myeloma cell migration via phosphatidylinositol 3-kinase/AKT/NF-kappa B signaling. Blood 2002; 101:2762-9. PubMed
  • Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Fanourakis G, Gu X, Bailey C, Joseph M, Libermann TA, Treon SP, Munshi NC, Richardson PG, Hideshima T, Anderson KC. Molecular sequelae of proteasome inhibition in human multiple myeloma cells. Proc Natl Acad Sci U S A 2002; 99:14374-9. PubMed
  • Castillo JJ, Treon SP, Davids MS. Inhibition of the Bruton Tyrosine Kinase Pathway in B-Cell Lymphoproliferative Disorders. Cancer J 2016; 22:34-9. PubMed
Hide