Photo of Irene M. Ghobrial,  MD

Irene M. Ghobrial, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-4198

Irene M. Ghobrial, MD

Dana-Farber Cancer Institute


  • Associate Professor, Medicine, Harvard Medical School
  • Active Medical Staff, Myeloma Program, Dana-Farber Cancer Institute


Research Abstract

My research focuses on understanding the regulation of cell trafficking and cell metastasis in malignancies that disseminate in the bone marrow such as Multiple Myeloma (MM) and Waldenstrom Macroglobulinemia (WM). I specifically focus on the role of the malignant bone marrow niche in disease progression from early precursor conditions like MGUS/smoldering MM to overt MM. We use MM as a model of bone metastasis and dissemination.

MM is a plasma cell dyscrasia characterized by the presence of multiple myelomatous “omas” throughout the skeleton indicating that there is continuous trafficking of tumor cells to multiple areas in the bone marrow niches. MM may therefore represent one of the best models to study cell trafficking or cell metastasis. Although the term “metastasis” is not commonly used to describe dissemination of hematological malignancies, my lab attempts to examine how MM can use a process of cell dissemination that is similar to cell trafficking of hematopoietic stem cell (HSCs) and cell metastasis in solid epithelial carcinomas. These studies can guide our understanding of the biological changes that occur during progression in MM.

The process of cell metastasis is described as a multistep process, the invasion-metastasis cascade. This involves cell invasion, intravasation into nearby blood vessels, passage into the circulation, followed by homing into predetermined distant tissues, the formation of new foci of micrometastases, and finally the growth of micrometastasis into macroscopic tumors. This review discusses the significant advances that have been discovered in the complex process of invasion-metastasis in epithelial carcinomas and cell trafficking in hematopoietic stem cells and how this process relates to progression in MM. This progression is mediated by clonal intrinsic factors that mediate tumor invasiveness as well as factors present in the tumor microenvironment that are permissive to oncogenic proliferation. Therapeutic agents that target the different steps of cell dissemination and progression are discussed. Despite the significant advances in the treatment of MM, better therapeutic agents that target this metastatic cascade are urgently needed.

To better examine in vivo localization of MM cells into the different niches of the bone marrow, we developed an imaging model to determine cell-cell interaction of tumor cells with the vascular niche or endosteal niche. Our group has shown that MM cells could be seen interacting with the endothelium of the calvarial bone marrow vasculature within minutes after intravenous injection into the tail vein of SCID mice using intravital confocal microscopy. We are currently examining the role of the malignant bone marrow niche and its components including stromal cells, endothelial cells and immune cells in regulating clonal evolution and tumor dissemination using a novel bone metastasis model with rainbow fluorescent 15 clone cell lines. In addition, we developed a novel in vitro bone marrow niche 3D model system to perform high-throughput screens such as RNAi or CRISPR screens as well as drug screens to examine interactions of stromal cells, endothelial cells and tumor cells.

We used the chemokine SDF-1 and its receptor CXCR4 as a model of understanding migration, homing and egress of MM and WM cells into and out of the marrow. We examined mechanisms of cell trafficking through the CXCR4/SDF-1 axis and downstream signaling proteins including the PI3K/Akt axis and Rho/Rac signaling. In addition, we identified a critical role of integrins, selectins and cadherins in regulating MM cell trafficking in vitro and in vivo. Moreover, we showed that hypoxia regulates cell dissemination and metastasis in MM through activation of transcription factors that modulate epithelial-mesenchymal transition (EMT), a process similar to that observed in solid tumor metastasis. Our recent data shows that activating mutation in CXCR4 (WHIM) in 20-30% of patients with WM leads to cell dissemination and drug resistance in WM cells and can be used to determine extramedullary disease in WM and drug resistance to PI3K, mTOR and BTK inhibitors. In addition, CXCR4 over-expression MM cells show extramedullary involvement and enhanced EMT-like transcriptional regulation that can be inhibited by a novel CXCR4 antibody inhibitor. Based on these studies, we have developed clinical trials using CXCR4 inhibitors in MM.

Although preparation of the pre-metastatic niche has not been studied in MM, we recently showed that stromal cells present in contact with MM cells secrete exosomes that modulate the growth and dissemination potential of MM cells. Our study showed that MM derived bone marrow stromal cells release exosomes, which are transferred to tumor cells, thereby resulting in modulation of tumor growth in vivo. Studies to define tumor derived exosomes and their role in preparing the pre-metastatic niche in MM are underway.

The lab is currently focusing on multiple aspects of cell metastasis or cell dissemination in MM and WM as tumor models for cell metastasis to the bone marrow niches: We are examining 1) mechanisms of early cell dissemination such as EMT transition and its epigenetic regulation, 2) the role of circulating tumor cells in cell dissemination, 3) preparation of the metastatic niche, 4) factors regulator progression of micrometastasis in patients with MGUS to overt MM, 5) miRNA regulators of tumor dissemination and stromal/myeloma interaction for cell dissemination, 6) Mechanisms of cell dissemination in extramedullary MM, 7) the role of hypoxia/metabolomics in regulating cell dissemination and drug resistance in MM.

In addition, our laboratory research data has been rapidly translated to innovative investigator-initiated clinical trials. We have conducted over 10 phase I and II clinical trials. Our studies on MM cell trafficking have been translated to the first chemosensitization trials in patients with Multiple Myeloma. In addition, I am the co-leader of the first consortium of clinical trials for blood cancers in collaboration with the Leukemia and Lymphoma Society to form the Blood Cancer Research Partnership (BCRP), a consortium for innovative clinical trials of 11 community oncology sites coordinated by DFCI. Moreover, we are initiating a new center for Prevention of Progression in Blood Cancers (BCP2) where patients with precursor conditions such as MGUS, early MDS and early CLL will be monitored propsectively for clonal evolution during disease progression. Clinical trials and research efforst will be coordinated for patients seen in this clinic to develop therapeutic agents that can prevent/delay disease progression in these early malignant conditions.

In support of the academic mission of Harvard Medical School, I am strongly involved in the teaching and training of our Internal Medicine Residents and Hematology/Oncology Fellows. I regularly give teaching lectures for Internal Medicine residents during their rotations on the Leukemia service and on morning teaching rounds. In addition, I am involved in the teaching of Hematology/Oncology fellows on regular basis and their academic career development. In addition, I am a mentor of Harvard Medical School/MIT students, The Continuing Umbrella of Research Experiences (CURE) program students as well as multiple postdoctoral fellows and students.



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  • Roccaro AM, Mishima Y, Sacco A, Moschetta M, Tai YT, Shi J, Zhang Y, Reagan MR, Huynh D, Kawano Y, Sahin I, Chiarini M, Manier S, Cea M, Aljawai Y, Glavey S, Morgan E, Pan C, Michor F, Cardarelli P, Kuhne M, Ghobrial IM. CXCR4 Regulates Extra-Medullary Myeloma through Epithelial-Mesenchymal-Transition-like Transcriptional Activation. Cell Rep 2015. PubMed
  • Reagan MR, Liaw L, Rosen CJ, Ghobrial IM. Dynamic interplay between bone and multiple myeloma: Emerging roles of the osteoblast. Bone 2015; 75:161-169. PubMed
  • Salem KZ, Ghobrial IM. The road to cure in multiple myeloma starts with smoldering disease. Expert Opin Orphan Drugs 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 Waldenstr旦m's macroglobulinemia. N Engl J Med 2015; 372:1430-40. PubMed
  • Weinstock M, Aljawai Y, Morgan EA, Laubach J, Gannon M, Roccaro AM, Varga C, Mitsiades CS, Paba-Prada C, Schlossman R, Munshi N, Anderson KC, Richardson PP, Weller E, Ghobrial IM. Incidence and clinical features of extramedullary multiple myeloma in patients who underwent stem cell transplantation. British Journal of Haematology 2015. PubMed
  • Glavey SV, Ghobrial IM. American Society of Hematology Annual Meeting 2014: highlights in multiple myeloma. Expert Rev Hematol 2015. PubMed
  • Maiso P, Huynh D, Moschetta M, Sacco A, Aljawai Y, Mishima Y, Asara JM, Roccaro AM, Kimmelman AC, Ghobrial IM. Metabolic signature identifies novel targets for drug resistance in Multiple Myeloma. Cancer Res 2015. PubMed
  • Leblebjian H, Noonan K, Paba-Prada C, Treon SP, Castillo JJ, Ghobrial IM. Cyclophosphamide, bortezomib and dexamethasone (CyBorD) combination in Waldenstrom Macroglobulinemia. Am J Hematol 2015. 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 Waldenstr旦m macroglobulinemia. Am J Hematol 2015; 90:100-4. PubMed
  • Glavey SV, Huynh D, Reagan MR, Manier S, Moschetta M, Kawano Y, Roccaro AM, Ghobrial IM, Joshi L, O'Dwyer ME. The cancer glycome: Carbohydrates as mediators of metastasis. Blood Rev. 2015. PubMed
  • Kawano Y, Moschetta M, Manier S, Glavey S, Görgün GT, Roccaro AM, Anderson KC, Ghobrial IM. Targeting the bone marrow microenvironment in multiple myeloma. Immunol Rev 2014; 263:160-72. PubMed
  • Castillo JJ, Ghobrial IM, Treon SP. Biology, prognosis, and therapy of Waldenstr旦m Macroglobulinemia. Cancer Treat Res 2015; 165:177-95. PubMed
  • Sahin I, Azab F, Mishima Y, Moschetta M, Tsang B, Glavey SV, Manier S, Zhang Y, Sacco A, Roccaro AM, Azab AK, Ghobrial IM. Targeting survival and cell trafficking in multiple myeloma and Waldenstrom macroglobulinemia using pan-class I PI3K inhibitor, buparlisib. Am J Hematol 2014; 89:1030-6. PubMed
  • Roccaro AM, Sacco A, Purschke WG, Moschetta M, Buchner K, Maasch C, Zboralski D, Zöllner S, Vonhoff S, Mishima Y, Maiso P, Reagan MR, Lonardi S, Ungari M, Facchetti F, Eulberg D, Kruschinski A, Vater A, Rossi G, Klussmann S, Ghobrial IM. SDF-1 Inhibition Targets the Bone Marrow Niche for Cancer Therapy. Cell Rep 2014; 9:118-28. PubMed
  • Ghobrial IM, Landgren O. How I treat smoldering multiple myeloma. Blood 2014. PubMed
  • Bianchi G, Ghobrial IM. Team Work Matters: Dual Inhibition Puts Non-Hodgkin Lymphoma Under Siege. Clin Cancer Res 2014. PubMed
  • Zingone A, Wang W, Corrigan-Cummins M, Wu SP, Plyler R, Korde N, Kwok M, Manasanch EE, Tageja N, Bhutani M, Mulquin M, Zuchlinski D, Yancey MA, Roschewski M, Zhang Y, Roccaro AM, Ghobrial IM, Calvo KR, Landgren O. Altered cytokine and chemokine profiles in multiple myeloma and its precursor disease. Cytokine 2014; 69:294-7. PubMed
  • Muz B, de la Puente P, Azab F, Ghobrial IM, Azab AK. Hypoxia Promotes Dissemination and Colonization in New Bone Marrow Niches in Waldenstrom's Macroglobulinemia. Mol Cancer Res 2014. PubMed
  • Zhang Y, Moschetta M, Huynh D, Tai YT, Zhang Y, Zhang W, Mishima Y, Ring JE, Tam WF, Xu Q, Maiso P, Reagan M, Sahin I, Sacco A, Manier S, Aljawai Y, Glavey S, Munshi NC, Anderson KC, Pachter J, Roccaro AM, Ghobrial IM. Pyk2 promotes tumor progression in multiple myeloma. Blood 2014. PubMed
  • Glavey SV, Manier S, Natoni A, Sacco A, Moschetta M, Reagan MR, Murillo LS, Sahin I, Wu P, Mishima Y, Zhang Y, Zhang W, Zhang Y, Morgan G, Joshi L, Roccaro AM, Ghobrial IM, O'Dwyer ME. The sialyltransferase ST3GAL6 influences homing and survival in multiple myeloma. Blood 2014; 124:1765-76. PubMed
  • Reagan MR, Mishima Y, Glavey SV, Zhang Y, Manier S, Lu ZN, Memarzadeh M, Zhang Y, Sacco A, Aljawai Y, Shi J, Tai YT, Ready JE, Kaplan DL, Roccaro AM, Ghobrial IM. Investigating osteogenic differentiation in multiple myeloma using a novel 3D bone marrow niche model. Blood 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 Waldenstr旦m macroglobulinemia (WM) and related disorders: IWWM-7 consensus. Blood 2014; 124:1404-11. PubMed
  • Azab AK, Sahin I, Azab F, Moschetta M, Mishima Y, Burwick N, Zimmermann J, Romagnoli B, Patel K, Chevalier E, Roccaro AM, Ghobrial IM. CXCR7-dependent angiogenic mononuclear cells trafficking regulates tumor progression in multiple myeloma. Blood 2014. PubMed
  • Swami A, Reagan MR, Basto P, Mishima Y, Kamaly N, Glavey S, Zhang S, Moschetta M, Seevaratnam D, Zhang Y, Liu J, Memarzadeh M, Wu J, Manier S, Shi J, Bertrand N, Lu ZN, Nagano K, Baron R, Sacco A, Roccaro AM, Farokhzad OC, Ghobrial IM. Engineered nanomedicine for myeloma and bone microenvironment targeting. Proc Natl Acad Sci U S A 2014. PubMed
  • Zabora J, Buzaglo J, Kennedy V, Richards T, Schapmire T, Zebrack B, Ghobrial IM. Clinical perspective: Linking psychosocial care to the disease continuum in patients with multiple myeloma. 2014. PubMed
  • Patel CG, Yee AJ, Scullen TA, Nemani N, Santo L, Richardson PG, Laubach JP, Ghobrial IM, Schlossman RL, Munshi NC, Anderson KC, Raje NS. Biomarkers of Bone Remodeling in Multiple Myeloma Patients to Tailor Bisphosphonate Therapy. Clin Cancer Res 2014. 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) is active and offers a neuropathy-sparing approach for proteasome-inhibitor based therapy in Waldenstrom's macroglobulinemia. Blood 2014. PubMed
  • Yee AJ, Hari P, Marcheselli R, Mahindra AK, Cirstea DD, Scullen TA, Burke JN, Rodig SJ, Hideshima T, Laubach JP, Ghobrial IM, Schlossman RL, Munshi NC, Anderson KC, Weller EA, Richardson PG, Raje NS. Outcomes in patients with relapsed or refractory multiple myeloma in a phase I study of everolimus in combination with lenalidomide. British Journal of Haematology 2014. PubMed
  • Roccaro AM, Sacco A, Jimenez C, Maiso P, Moschetta M, Mishima Y, Aljawai Y, Sahin I, Kuhne M, Cardarelli P, Cohen L, San Miguel JF, Garcia-Sanz R, Ghobrial IM. C1013G/CXCR4 acts as a driver mutation of tumor progression and modulator of drug resistance in lymphoplasmacytic lymphoma. Blood 2014. PubMed
  • Moschetta M, Mishima Y, Sahin I, Manier S, Glavey S, Vacca A, Roccaro AM, Ghobrial IM. Role of endothelial progenitor cells in cancer progression. Biochim Biophys Acta 2014; 1846:26-39. PubMed
  • Bouyssou JM, Manier S, Huynh D, Issa S, Roccaro AM, Ghobrial IM. Regulation of microRNAs in cancer metastasis. Biochim Biophys Acta 2014; 1845:255-265. PubMed
  • Richardson PG, Xie W, Jagannath S, Jakubowiak A, Lonial S, Raje NS, Alsina M, Ghobrial IM, Schlossman RL, Munshi NC, Mazumder A, Vesole DH, Kaufman JL, Colson K, McKenney M, Lunde LE, Feather J, Maglio ME, Warren D, Francis D, Hideshima T, Knight R, Esseltine DL, Mitsiades CS, Weller E, Anderson KC. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood 2014; 123:1461-9. 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. Waldenstr旦m macroglobulinemia: from biology to treatment. Expert Rev Hematol 2014; 7:157-68. PubMed
  • Zhang W, Wang YE, Zhang Y, Leleu X, Reagan M, Zhang Y, Mishima Y, Glavey S, Manier S, Sacco A, Jiang B, Roccaro AM, Ghobrial IM. Global Epigenetic Regulation of MicroRNAs in Multiple Myeloma. PLoS ONE 2014; 9:e110973. PubMed
  • Corcoran C, Rani S, Breslin S, Gogarty M, Ghobrial IM, Crown J, O'Driscoll L. miR-630 targets IGF1R to regulate response to HER-targeting drugs and overall cancer cell progression in HER2 over-expressing breast cancer. Mol Cancer 2014; 13:71. PubMed
  • Roccaro AM, Sacco A, Maiso P, Azab AK, Tai YT, Reagan M, Azab F, Flores LM, Campigotto F, Weller E, Anderson KC, Scadden DT, Ghobrial IM. BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression. J Clin Invest 2013; 123:1542-55. PubMed
  • Ghobrial IM. Update on Waldenstr旦m's Macroglobulinemia. Clin Adv Hematol Oncol 2013; 11:244-6. PubMed
  • Ghobrial IM. Correspondence: Revisiting treatment paradigms in high-risk smoldering multiple myeloma: out with the old, in with the new? Leuk Lymphoma 2013. PubMed
  • Richardson PG, Siegel D, Baz R, Kelley SL, Munshi NC, Laubach J, Sullivan D, Alsina M, Schlossman R, Ghobrial IM, Doss D, Loughney N, McBride L, Bilotti E, Anand P, Nardelli L, Wear S, Larkins G, Chen M, Zaki MH, Jacques C, Anderson KC. Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib. Blood 2013; 121:1961-7. PubMed
  • Sacco A, Zhang Y, Maiso P, Manier S, Rossi G, Treon SP, Ghobrial IM, Roccaro AM. microRNA Aberrations in Waldenstr旦m Macroglobulinemia. Clin Lymphoma Myeloma Leuk 2013. PubMed
  • Agarwal A, Ghobrial IM. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: a review of the current understanding of epidemiology, biology, risk stratification, and management of myeloma precursor disease. Clin Cancer Res 2013; 19:985-94. PubMed
  • Ghobrial IM, Campigotto F, Murphy TJ, Boswell EN, Banwait R, Azab F, Chuma S, Kunsman J, Donovan A, Masood F, Warren D, Rodig S, Anderson KC, Richardson PG, Weller E, Matous J. Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenstr旦m macroglobulinemia. Blood 2013; 121:1296-303. PubMed
  • Rosovsky R, Hong F, Tocco D, Connell B, Mitsiades C, Schlossman R, Ghobrial I, Lockridge L, Warren D, Bradwin G, Doyle M, Munshi N, Soiffer RJ, Anderson KC, Weller E, Richardson P. Endothelial stress products and coagulation markers in patients with multiple myeloma treated with lenalidomide plus dexamethasone: an observational study. British Journal of Haematology 2013; 160:351-8. PubMed
  • Ghobrial IM. Choice of therapy for patients with Waldenstrom macroglobulinemia. J Clin Oncol 2013; 31:291-3. PubMed
  • Liu Y, Quang P, Braggio E, Ngo H, Badalian-Very G, Flores L, Zhang Y, Sacco A, Maiso P, Azab AK, Azab F, Carrasco R, Rollins BJ, Roccaro AM, Ghobrial IM. Novel tumor suppressor function of glucocorticoid-induced TNF receptor GITR in multiple myeloma. PLoS ONE 2013; 8:e66982. PubMed
  • Weinstock M, Ghobrial IM. Extramedullary multiple myeloma. Leuk Lymphoma 2013. 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 Waldenstr旦m macroglobulinaemia: update from the VIth International Workshop. British Journal of Haematology 2012. PubMed
  • Roccaro AM, Sacco A, Jia X, Banwait R, Maiso P, Azab F, Flores L, Manier S, Azab AK, Ghobrial IM. Mechanisms of Activity of the TORC1 Inhibitor Everolimus in Waldenstrom Macroglobulinemia. Clin Cancer Res 2012. PubMed
  • Maiso P, Ghobrial IM. Would the real myeloma cell please stand up? Leuk Lymphoma 2012; 53:1851-2. PubMed
  • Bianchi G, Ghobrial IM. Molecular mechanisms of effectiveness of novel therapies in multiple myeloma. Leuk Lymphoma 2012. PubMed
  • Ghobrial IM, Moreau P, Harris B, Poon T, Jourdan E, Maisonneuve H, Benhadji KA, Hossain AM, Nguyen TS, Wooldridge JE, Leblond V. A multicenter phase II study of single-agent enzastaurin in previously treated Waldenstrom macroglobulinemia. Clin Cancer Res 2012; 18:5043-50. PubMed
  • Reagan MR, Seib FP, McMillin DW, Sage EK, Mitsiades CS, Janes SM, Ghobrial IM, Kaplan DL. Stem Cell Implants for Cancer Therapy: TRAIL-Expressing Mesenchymal Stem Cells Target Cancer Cells In Situ. J Breast Cancer 2012; 15:273-82. PubMed
  • Zhang Y, Roccaro AM, Rombaoa C, Flores L, Obad S, Fernandes SM, Sacco A, Liu Y, Ngo H, Quang P, Azab AK, Azab F, Maiso P, Reagan M, Brown JR, Thai TH, Kauppinen S, Ghobrial IM. LNA-mediated anti-miR-155 silencing in low-grade B-cell lymphomas. Blood 2012; 120:1678-86. PubMed
  • Ghobrial IM. Myeloma as a model for the process of metastasis: implications for therapy. Blood 2012; 120:20-30. PubMed
  • Ghobrial IM. Are you sure this is Waldenstrom macroglobulinemia? Hematology Am Soc Hematol Educ Program 2012; 2012:586-94. PubMed
  • Sacco A, Aujay M, Morgan B, Azab AK, Maiso P, Liu Y, Zhang Y, Azab F, Ngo HT, Issa GC, Quang P, Roccaro AM, Ghobrial IM. Carfilzomib-Dependent Selective Inhibition of the Chymotrypsin-like Activity of the Proteasome Leads to Antitumor Activity in Waldenstrom's Macroglobulinemia. Clin Cancer Res 2011; 17:1753-64. PubMed
  • Leleu XP, Xie W, Bagshaw M, Banwait R, Leduc R, Roper N, Weller E, Ghobrial IM. The Role of Serum Immunoglobulin Free Light Chain (sFLC) in response and progression in Waldenstrom Macroglobulinemia (WM). Clin Cancer Res 2011. PubMed
  • Ghobrial IM, Weller E, Vij R, Munshi NC, Banwait R, Bagshaw M, Schlossman R, Leduc R, Chuma S, Kunsman J, Laubach J, Jakubowiak AJ, Maiso P, Roccaro A, Armand P, Dollard A, Warren D, Harris B, Poon T, Sam A, Rodig S, Anderson KC, Richardson PG. Weekly bortezomib in combination with temsirolimus in relapsed or relapsed and refractory multiple myeloma: a multicentre, phase 1/2, open-label, dose-escalation study. Lancet Oncol 2011; 12:263-72. PubMed
  • Sacco A, Maiso P, Azab A, Azab F, Zhang Y, Liu Y, Ngo HT, Morgan B, Quang P, Issa G, Ghobrial IM, Roccaro AM. Key Role of MicroRNAs in Waldenstr旦m's Macroglobulinemia Pathogenesis. Clin Lymphoma Myeloma Leuk 2011; 11:109-11. PubMed
  • Ghobrial IM, Zhang Y, Liu Y, Ngo H, Azab F, Sacco A, Azab A, Maiso P, Morgan B, Quang P, Issa G, Roccaro A. The Bone Marrow Niche in Waldenstr旦m's Macroglobulinemia. Clin Lymphoma Myeloma Leuk 2011; 11:118-20. PubMed
  • Leleu X, Koulieris E, Maltezas D, Itzykson R, Xie W, Manier S, Dulery R, Boyle E, Gauthier J, Poulain S, Tatiana T, Panayiotidis P, Bradwell AR, Harding S, Leblond V, Kyrtsonis MC, Ghobrial IM. Novel M-Component Based Biomarkers in Waldenstr旦m's Macroglobulinemia. Clin Lymphoma Myeloma Leuk 2011; 11:164-7. PubMed
  • Calvo KR, Landgren O, Roccaro AM, Ghobrial IM. Role of microRNAs from monoclonal gammopathy of undetermined significance to multiple myeloma. Semin Hematol 2011; 48:39-45. PubMed
  • Roper N, Deangelo DJ, Kuo F, Cin PD, Ghobrial I, Aster JC. An asymptomatic 61-year-old man with BCR-ABL-positive bone marrow following autologous transplantation for multiple myeloma. Am J Hematol 2010; 85:944-6. PubMed
  • Sacco A, Roccaro A, Ghobrial IM. Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's Macroglobulinemia. 2011; 1:578-82. PubMed
  • Rourke M, Anderson KC, Ghobrial IM. Review of clinical trials conducted in Waldenstrom macroglobulinemia and recommendations for reporting clinical trial responses in these patients. Leuk Lymphoma 2010; 51:1779-92. PubMed
  • Roccaro AM, Sacco A, Jia X, Azab AK, Maiso P, Ngo HT, Azab F, Runnels J, Quang P, Ghobrial IM. microRNA-dependent modulation of histone acetylation in Waldenstrom macroglobulinemia. Blood 2010; 116:1506-14. 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
  • Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, Avigan DE, Xie W, Ghobrial IM, Schlossman RL, Mazumder A, Munshi NC, Vesole DH, Joyce R, Kaufman JL, Doss D, Warren DL, Lunde LE, Kaster S, Delaney C, Hideshima T, Mitsiades CS, Knight R, Esseltine DL, Anderson KC. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 2010; 116:679-86. 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
  • Roccaro AM, Sacco A, Aujay M, Ngo HT, Azab AK, Azab F, Quang P, Maiso P, Runnels J, Anderson KC, Demo S, Ghobrial IM. Selective inhibition of chymotrypsin-like activity of the immunoproteasome and constitutive proteasome in Waldenstrom macroglobulinemia. Blood 2010; 115:4051-60. 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
  • Richardson PG, Laubach J, Mitsiades C, Schlossman RL, Doss D, Colson K, McKenney ML, Noonan K, Warren DL, Ghobrial IM, Munshi NC, Anderson K. Tailoring treatment for multiple myeloma patients with relapsed and refractory disease. Oncology (Huntingt) 2010; 24:22-9. PubMed
  • Ghobrial IM, Roccaro A, Hong F, Weller E, Rubin N, Leduc R, Rourke M, Chuma S, Sacco A, Jia X, Azab F, Azab AK, Rodig S, Warren D, Harris B, Varticovski L, Sportelli P, Leleu X, Anderson KC, Richardson PG. Clinical and translational studies of a phase II trial of the novel oral Akt inhibitor perifosine in relapsed or relapsed/refractory Waldenstrom's macroglobulinemia. Clin Cancer Res 2010; 16:1033-41. PubMed
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  • Ngo HT, Azab AK, Farag M, Jia X, Melhem MM, Runnels J, Roccaro AM, Azab F, Sacco A, Leleu X, Anderson KC, Ghobrial IM. Src tyrosine kinase regulates adhesion and chemotaxis in Waldenstrom macroglobulinemia. Clin Cancer Res 2009; 15:6035-41. PubMed
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  • Roccaro AM,Sacco A,Thompson B,Leleu X,Azab AK,Azab F,Runnels J,Jia X,Ngo HT,Melhem MR,Lin CP,Ribatti D,Rollins BJ,Witzig TE,Anderson KC,Ghobrial IM. microRNAs 15a and 16 regulate tumor proliferation in multiple myeloma. Blood 2009; 113:6669-80. PubMed
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  • Braggio E,Keats JJ,Leleu X,Van Wier S,Jimenez-Zepeda VH,Valdez R,Schop RF,Price-Troska T,Henderson K,Sacco A,Azab F,Greipp P,Gertz M,Hayman S,Rajkumar SV,Carpten J,Chesi M,Barrett M,Stewart AK,Dogan A,Bergsagel PL,Ghobrial IM,Fonseca R. Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenstrom's macroglobulinemia. Cancer Res 2009; 69:3579-88. PubMed
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