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1. New drugs and novel mechanisms of action in multiple myeloma in 2013: a report from the International Myeloma Working Group (IMWG)

Author

Ocio, E M, Richardson, P G, Rajkumar, S V, Palumbo, A, Mateos, M V, Orlowski, R, Kumar, S, Usmani, S, Roodman, D, Niesvizky, R, Einsele, H, Anderson, K C, Dimopoulos, M A, Avet-Loiseau, H, Mellqvist, U-H, Turesson, I, Merlini, G, Schots, R, McCarthy, P, Bergsagel, L, Chim, C S, Lahuerta, J J, Shah, J, Reiman, A, Mikhael, J, Zweegman, S, Lonial, S, Comenzo, R, Chng, W J, Moreau, P, Sonneveld, P, Ludwig, H, Durie, B G M, and Miguel, J F S

Published
2014
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4. International myeloma working group recommendations for the diagnosis and management of myeloma-related renal impairment

Author

Dimopoulos, M.A. Sonneveld, P. Leung, N. Merlini, G. Ludwig, H. Kastritis, E. Goldschmidt, H. Joshua, D. Orlowski, R.Z. Powles, R. Vesole, D.H. Garderet, L. Einsele, H. Palumbo, A. Cavo, M. Richardson, P.G. Moreau, P. Miguel, J.S. Vincent Rajkumar, S. Durie, B.G.M. Terpos, E. Abildgaard, N. Abonour, R. Alsina, M. Anderson, K.C. Attal, M. Avet-Loiseau, H. Badros, A. Bahlis, N.J. Barlogie, B. Bataille, R. Beksaç, M. Belch, A. Ben-Yehuda, D. Bensinger, B. Leif Bergsagel, P. Bhutani, M. Bird, J. Bladé, J. Broijl, A. Boccadoro, M. Caers, J. Chanan-Khan, A. Chari, A. Chen, W.M. Chesi, M. Anthony Child, J. Chim, C.S. Chng, W.-J. Comenzo, R. Cook, G. Crowley, J. Crusoe, E. Dalton, W. Lee Moffitt, H. Davies, F. de la Rubia, J. de Souza, C. Delforge, M. Dhodapkar, M. Dispenzieri, A. Drach, J. Drake, M. Du, J. Dytfeld, D. Facon, T. Fantl, D. Fermand, J.-P. Fernández de Larrea, C. Fonseca, R. Gahrton, G. Garćia-Sanz, R. Gasparetto, C. Gertz, M. Ghobrial, I. Gibson, J. Gimsing, P. Giralt, S. Gu, J. Hajek, R. Hardan, I. Hari, P. Hata, H. Hattori, Y. Heffner, T. Hillengass, J. Ho, J. Hoering, A. Hoffman, J.E. Hou, J. Huang, J. Hungria, V. Ida, S. Jagannath, S. Jakubowiak, A.J. Johnsen, H.E. Jurczyszyn, A. Kaiser, M. Kaufman, J. Kawano, M. Korde, N. Kovacs, E. Krishnan, A. Kristinsson, S. Kröger, N. Kumar, S. Kyle, R.A. Kyriacou, C. Lacy, M. Lahuerta, J.J. Landgren, O. Larocca, A. Laubach, J. da Costa, F.L. Lee, J.-H. Leiba, M. Leleu, X. Lentzsch, S. Lokhorst, H. Lonial, S. Lu, J. Mahindra, A. Maiolino, A. Manasanch, E.E. Mark, T. Mateos, M.-V. Mazumder, A. McCarthy, P. Mehta, J. Mellqvist, U.-H. Mikhael, J. Morgan, G. Munshi, N. Nahi, H. Nawarawong, W. Niesvizky, R. Nouel, A. Novis, Y. Ocio, E. O'Dwyer, M. O'Gorman, P. Orfao, A. Otero, P.R. Paiva, B. Pavlovsky, S. Pilarski, L. Pratt, G. Qui, L. Raje, N. Reece, D. Reiman, A. Remaggi, G. Richter, J. Serra, E.R. Morales, A.R. Romeril, K.R. Roodman, D. Rosiñol, L. Rossi, A. Roussel, M. Russell, S. Schjesvold, F. Schots, R. Sevcikova, S. Sezer, O. Shah, J.J. Shimizu, K. Shustik, C. Siegel, D. Singhal, S. Spencer, A. Stadtmauer, E. Stewart, K. Tan, D. Terragna, C. Tosi, P. Tricot, G. Turesson, I. Usmani, S. Van Camp, B. Van de Donk, N. Van Ness, B. Van Riet, I. Broek, I.V. Vanderkerken, K. Vescio, R. Vij, R. Voorhees, P. Waage, A. Wang, M. Weber, D. Weiss, B.M. Westin, J. Wheatley, K. Zamagni, E. Zonder, J. Zweegman, S.

Abstract

Purpose: The aim of the International Myeloma Working Group was to develop practical recommendations for the diagnosis and management of multiple myeloma–related renal impairment (RI). Methods: Recommendations were based on published data through December 2015, and were developed using the system developed by the Grading of Recommendation, Assessment, Development, and Evaluation Working Group. Recommendations: All patients with myeloma at diagnosis and at disease assessment should have serum creatinine, estimated glomerular filtration rate, and electrolytes measurements as well as free light chain, if available, and urine electrophoresis of a sample from a 24-hour urine collection (grade A). The Chronic Kidney Disease Epidemiology Collaboration, preferably, or the Modification of Diet in Renal Disease formula should be used for the evaluation of estimated glomerular filtration rate in patients with stabilized serum creatinine (grade A). International Myeloma Working Group criteria for renal reversibility should be used (grade B). For the management of RI in patients with multiple myeloma, high fluid intake is indicated along with antimyeloma therapy (grade B). The use of high-cutoff hemodialysis membranes in combination with antimyeloma therapy can be considered (grade B). Bortezomib-based regimens remain the cornerstone of the management of myeloma-related RI (grade A). High-dose dexamethasone should be administered at least for the first month of therapy (grade B). Thalidomide is effective in patients with myeloma with RI, and no dose modifications are needed (grade B). Lenalidomide is effective and safe, mainly in patients with mild to moderate RI (grade B); for patients with severe RI or on dialysis, lena-lidomide should be given with close monitoring for hematologic toxicity (grade B) with dose reduction as needed. High-dose therapy with autologous stem cell transplantation (with melphalan 100 mg/m2 to 140 mg/m2) is feasible in patients with RI (grade C). Carfilzomib can be safely administered to patients with creatinine clearance > 15 mL/min, whereas ixazomib in combination with lenalidomide and dex-amethasone can be safely administered to patients with creatinine clearance > 30 mL/min (grade A). © 2016 by American Society of Clinical Oncology.

Published
2016

7. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib:A multicenter international myeloma working group study

Author

Kumar S. K., Lee J. H., Lahuerta J. J., Morgan G., Richardson P. G., Crowley J., Haessler J., Feather J., Hoering A., Moreau P., LeLeu X., Hulin C., Klein S. K., Sonneveld P., Siegel D., Bladé J., Goldschmidt H., Jagannath S., Miguel J. S., Orlowski R., Palumbo A., Sezer O., Rajkumar S. V., Durie B. G. International Myeloma Working Group Abildgaard N, Abonour R, Alexanian R, Alsina M, Anderson KC, Attal M, Avet Loiseau H, Badros A, Baris D, Barlogie B, Bataille R, Beksaç M, Belch A, Ben Yehuda D, Bensinger B, Bergsagel PL, Bird J, Bladé J, Boccadoro M, Chanan Khan A, Chen WM, Child T, Chim J, Chng WJ, Comenzo R, Crowley J, Dalton W, Davies F, de Souza C, Delforge M, Dimopoulos M, Dispenzieri A, Drach J, Drake M, Durie BG, Einsele H, Facon T, Fantl D, Fermand JP, Fonseca R, Gahrton G, García Sanz R, Gasparetto C, Gertz M, Gibson J, Giralt S, Goldschmidt H, Greipp P, Hajek R, Hardan I, Hari P, Harousseau JL, Hata H, Hattori Y, Heffner T, Ho J, Hungria V, Ida S, Jacobs P, Jagannath S, Johnsen HE, Jian H, Joshua D, Jurczyszyn A, Kawano M, Kröger N, Kumar S, Kyle RA, Lacy M, Lahuerta JJ, Landgren O, Laubach J, Lee JH, LeLeu X, Lentzsch S, Lokhorst H, Lonial S, Ludwig H, Maiolino A, Mateos M, Mehta J, Mellqvist UH, Merlini G, Mikhael J, Morales AR, Moreau P, Morgan G, Nahi H, Munshi N, Niesvizky R, Nouel A, Novis Y, Orlowski R, Palumbo A, Pavlovsky S, Pilarski L, Powles R, Raje N, Rajkumar SV, Reece D, Reiman T, Richardson PG, Roodman D, Rosiñol L, San Miguel J, Sezer O, Shah JJ, Shaughnessy J, Shimizu K, Shustik C, Siegel D, Singhal S, Sonneveld P, Spencer A, Stadtmauer E, Stewart K, Terpos E, Tosi P, Tricot G, Turesson I, Van Camp B, Van Ness B, Van Riet I, Vande Broek I, Vanderkerken K, Vescio R, Vesole D, Waage A, Wang M, Weber D, Westin J, Wheatley K, Zonder J., CAVO, MICHELE, Kumar S.K., Lee J.H., Lahuerta J.J., Morgan G., Richardson P.G., Crowley J., Haessler J., Feather J., Hoering A., Moreau P., LeLeu X., Hulin C., Klein S.K., Sonneveld P., Siegel D., Bladé J., Goldschmidt H., Jagannath S., Miguel J.S., Orlowski R., Palumbo A., Sezer O., Rajkumar S.V., Durie B.G. International Myeloma Working Group Abildgaard N, Abonour R, Alexanian R, Alsina M, Anderson KC, Attal M, Avet-Loiseau H, Badros A, Baris D, Barlogie B, Bataille R, Beksaç M, Belch A, Ben-Yehuda D, Bensinger B, Bergsagel PL, Bird J, Bladé J, Boccadoro M, Cavo M, Chanan-Khan A, Chen WM, Child T, Chim J, Chng WJ, Comenzo R, Crowley J, Dalton W, Davies F, de Souza C, Delforge M, Dimopoulos M, Dispenzieri A, Drach J, Drake M, Durie BG, Einsele H, Facon T, Fantl D, Fermand JP, Fonseca R, Gahrton G, García-Sanz R, Gasparetto C, Gertz M, Gibson J, Giralt S, Goldschmidt H, Greipp P, Hajek R, Hardan I, Hari P, Harousseau JL, Hata H, Hattori Y, Heffner T, Ho J, Hungria V, Ida S, Jacobs P, Jagannath S, Johnsen HE, Jian H, Joshua D, Jurczyszyn A, Kawano M, Kröger N, Kumar S, Kyle RA, Lacy M, Lahuerta JJ, Landgren O, Laubach J, Lee JH, LeLeu X, Lentzsch S, Lokhorst H, Lonial S, Ludwig H, Maiolino A, Mateos M, Mehta J, Mellqvist UH, Merlini G, Mikhael J, Morales AR, Moreau P, Morgan G, Nahi H, Munshi N, Niesvizky R, Nouel A, Novis Y, Orlowski R, Palumbo A, Pavlovsky S, Pilarski L, Powles R, Raje N, Rajkumar SV, Reece D, Reiman T, Richardson PG, Roodman D, Rosiñol L, San Miguel J, Sezer O, Shah JJ, Shaughnessy J, Shimizu K, Shustik C, Siegel D, Singhal S, Sonneveld P, Spencer A, Stadtmauer E, Stewart K, Terpos E, Tosi P, Tricot G, Turesson I, Van Camp B, Van Ness B, Van Riet I, Vande Broek I, Vanderkerken K, Vescio R, Vesole D, Waage A, Wang M, Weber D, Westin J, Wheatley K, Zonder J., and Hematology

Subjects
Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, NATURAL HISTORY, Antineoplastic Agents, Context (language use), RELAPSE, Article, Recurrence, Internal medicine, medicine, Humans, Immunologic Factors, Elotuzumab, Survival analysis, Multiple myeloma, Aged, Aged, 80 and over, Isatuximab, Bortezomib, business.industry, Hematology, Middle Aged, Pomalidomide, medicine.disease, Survival Analysis, Surgery, Regimen, SURVIVAL, Disease Progression, Female, Multiple Myeloma, business, medicine.drug
Abstract

Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T-0). The median age at diagnosis was 58 years, and time from diagnosis to T-0 was 3.3 years. Following T-0, 213 (74%) patients had a treatment recorded with one or more regimens (median = 1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (44%) including >= partial response in 69 (32%). The median overall survival and event-free survival from T-0 were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs. Leukemia (2012) 26, 149-157; doi:10.1038/leu.2011.196; published online 29 July 2011

Published
2012

8. New drugs and novel mechanisms of action in multiple myeloma in 2013: A report from the International Myeloma Working Group (IMWG)

Author

Ocio, E.M. Richardson, P.G. Rajkumar, S.V. Palumbo, A. Mateos, M.V. Orlowski, R. Kumar, S. Usmani, S. Roodman, D. Niesvizky, R. Einsele, H. Anderson, K.C. Dimopoulos, M.A. Avet-Loiseau, H. Mellqvist, U.-H. Turesson, I. Merlini, G. Schots, R. Mccarthy, P. Bergsagel, L. Chim, C.S. Lahuerta, J.J. Shah, J. Reiman, A. Mikhael, J. Zweegman, S. Lonial, S. Comenzo, R. Chng, W.J. Moreau, P. Sonneveld, P. Ludwig, H. Durie, B.G.M. Miguel, J.F.S.

Abstract

Treatment in medical oncology is gradually shifting from the use of nonspecific chemotherapeutic agents toward an era of novel targeted therapy in which drugs and their combinations target specific aspects of the biology of tumor cells. Multiple myeloma (MM) has become one of the best examples in this regard, reflected in the identification of new pathogenic mechanisms, together with the development of novel drugs that are being explored from the preclinical setting to the early phases of clinical development. We review the biological rationale for the use of the most important new agents for treating MM and summarize their clinical activity in an increasingly busy field. First, we discuss data from already approved and active agents (including second- and third-generation proteasome inhibitors (PIs), immunomodulatory agents and alkylators). Next, we focus on agents with novel mechanisms of action, such as monoclonal antibodies (MoAbs), cell cycle-specific drugs, deacetylase inhibitors, agents acting on the unfolded protein response, signaling transduction pathway inhibitors and kinase inhibitors. Among this plethora of new agents or mechanisms, some are specially promising: anti-CD38 MoAb, such as daratumumab, are the first antibodies with clinical activity as single agents in MM. Moreover, the kinesin spindle protein inhibitor Arry-520 is effective in monotherapy as well as in combination with dexamethasone in heavily pretreated patients. Immunotherapy against MM is also being explored, and probably the most attractive example of this approach is the combination of the anti-CS1 MoAb elotuzumab with lenalidomide and dexamethasone, which has produced exciting results in the relapsed/refractory setting. © 2014 Macmillan Publishers Limited.

Published
2014

9. The role of vertebral augmentation in multiple myeloma: International Myeloma Working Group Consensus Statement

Author

Hussein M. A., Vrionis F. D., Allison R., Berenson J., Berven S., Erdem E., Giralt S., Jagannath S., Kyle R. A., LeGrand S., Pflugmacher R., Raje N., Rajkumar S. V., Randall R. L., Roodman D., Siegel D., Vescio R., Zonder J., Durie B. G., International Myeloma Working Group, Cavo M, Hussein M.A., Vrionis F.D., Allison R., Berenson J., Berven S., Erdem E., Giralt S., Jagannath S., Kyle R.A., LeGrand S., Pflugmacher R., Raje N., Rajkumar S.V., Randall R.L., Roodman D., Siegel D., Vescio R., Zonder J., Durie B.G., International Myeloma Working Group [.., Cavo M, ], Faculty of Law and Criminology, and Private and Economic Law

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Consensus, Polymethyl methacrylate, Statement (logic), health care facilities, manpower, and services, education, Multiple Myeloma/complications, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Lymphoid neoplasms, health care economics and organizations, Multiple myeloma, Hematology, business.industry, medicine.disease, B-cell neoplasm, Surgery, minimally invasive surgical procedures, Spinal Fractures/complications, oncology, business, Polymethyl Methacrylate/administration & dosage
Abstract

The role of vertebral augmentation in multiple myeloma: International Myeloma Working Group Consensus Statement

Published
2008

10. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib

Author

Kumar, Sk, Lee, Jh, Lahuerta, Jj, Morgan, G, Richardson, Pg, Crowley, J, Haessler, J, Feather, J, Hoering, A, Moreau, P, Leleu, X, Hulin, C, Klein, Sk, Sonneveld, P, Siegel, D, Bladé, J, Goldschmidt, H, Jagannath, S, Miguel, Js, Orlowski, R, Palumbo, Antonio, Sezer, O, Rajkumar, Sv, Durie, Bg, on behalf of the International Myeloma Working Group, International Myeloma Working Group, Abildgaard, N, Abonour, R, Alexanian, R, Alsina, M, Anderson, Kc, Attal, M, Avet Loiseau, H, Badros, A, Baris, D, Barlogie, B, Bataille, R, Beksaç, M, Belch, A, Ben Yehuda, D, Bensinger, B, Leif Bergsagel, P, Bird, J, Boccadoro, M, Cavo, M, Chanan Khan, A, Ming Chen, W, Child, T, Chim, J, Chng, Wj, Comenzo, R, Dalton, W, Davies, F, de Souza, C, Delforge, M, Dimopoulos, M, Dispenzieri, A, Drach, J, Drake, M, Einsele, H, Facon, T, Fantl, D, Fermand, Jp, Fonseca, R, Gahrton, G, García Sanz, R, Gasparetto, C, Gertz, M, Gibson, J, Giralt, S, Greipp, P, Hajek, R, Hardan, I, Hari, P, Harousseau, Jl, Hata, H, Hattori, Y, Heffner, T, Ho, J, Hungria, V, Ida, S, Jacobs, P, Johnsen, H, Jian, H, Joshua, D, Jurczyszyn, A, Kawano, M, Kröger, N, Kumar, S, Kyle, Ra, Lacy, M, Landgren, O, Laubach, J, Lentzsch, S, Lokhorst, H, Lonial, S, Ludwig, H, Maiolino, A, Mateos, M, Mehta, J, Mellqvist, Uh, Merlini, G, Mikhael, J, Morales, Ar, Nari, H, Munshi, N, Niesvizky, R, Nouel, A, Novis, Y, Palumbo, A, Pavlovsky, S, Pilarski, L, Powles, R, Raje, N, Vincent Rajkumar, S, Reece, D, Reiman, T, Roodman, D, Rosiñol, L, Shah, Jj, Shaughnessy, J, Shimizu, K, Shustik, C, Singhal, S, Spencer, A, Stadtmauer, E, Stewart, K, Terpos, E, Tosi, P, Tricot, G, Turesson, I, Van Camp, B, Van Ness, B, Van Riet, I, Broek, Iv, Vanderkerken, K, Vescio, R, Vesole, D, Waage, A, Wang, M, Weber, D, Westin, J, Wheatley, K, and Zonder, J.

Published
2012

11. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: A multicenter international myeloma working group study

Author

Kumar, Sk, Lee, Jh, Lahuerta, Jj, Morgan, G, Richardson, Pg, Crowley, J, Haessler, J, Feather, J, Hoering, A, Moreau, P, Leleu, X, Hulin, C, Klein, Sk, Sonneveld, P, Siegel, D, Bladé, J, Goldschmidt, H, Jagannath, S, Miguel, Js, Orlowski, R, Palumbo, Antonio, Sezer, O, Rajkumar, Sv, Durie, Bg, on behalf of the International Myeloma Working Group, International Myeloma Working Group, Abildgaard, N, Abonour, R, Alexanian, R, Alsina, M, Anderson, Kc, Attal, M, Avet Loiseau, H, Badros, A, Baris, D, Barlogie, B, Bataille, R, Beksaç, M, Belch, A, Ben Yehuda, D, Bensinger, B, Leif Bergsagel, P, Bird, J, Boccadoro, M, Cavo, M, Chanan Khan, A, Ming Chen, W, Child, T, Chim, J, Chng, Wj, Comenzo, R, Dalton, W, Davies, F, de Souza, C, Delforge, M, Dimopoulos, M, Dispenzieri, A, Drach, J, Drake, M, Einsele, H, Facon, T, Fantl, D, Fermand, Jp, Fonseca, R, Gahrton, G, García Sanz, R, Gasparetto, C, Gertz, M, Gibson, J, Giralt, S, Greipp, P, Hajek, R, Hardan, I, Hari, P, Harousseau, Jl, Hata, H, Hattori, Y, Heffner, T, Ho, J, Hungria, V, Ida, S, Jacobs, P, Johnsen, H, Jian, H, Joshua, D, Jurczyszyn, A, Kawano, M, Kröger, N, Kumar, S, Kyle, Ra, Lacy, M, Landgren, O, Laubach, J, Lentzsch, S, Lokhorst, H, Lonial, S, Ludwig, H, Maiolino, A, Mateos, M, Mehta, J, Mellqvist, Uh, Merlini, G, Mikhael, J, Morales, Ar, Nari, H, Munshi, N, Niesvizky, R, Nouel, A, Novis, Y, Palumbo, A, Pavlovsky, S, Pilarski, L, Powles, R, Raje, N, Vincent Rajkumar, S, Reece, D, Reiman, T, Roodman, D, Rosiñol, L, Shah, Jj, Shaughnessy, J, Shimizu, K, Shustik, C, Singhal, S, Spencer, A, Stadtmauer, E, Stewart, K, Terpos, E, Tosi, P, Tricot, G, Turesson, I, Van Camp, B, Van Ness, B, Van Riet, I, Broek, Iv, Vanderkerken, K, Vescio, R, Vesole, D, Waage, A, Wang, M, Weber, D, Westin, J, Wheatley, K, and Zonder, J.

Published
2011

12. New drugs and novel mechanisms of action in multiple myeloma in 2013: A report from the International Myeloma Working Group (IMWG)

Author

Ocio, E.M. (E.), Richardson, P.G. (Paul Gerard), Rajkumar, S.V. (Vincent), Palumbo, A. (Antonio), Mateos, M.V., Orlowski, R. (R.), Kumar, S. (Shaji), Usmani, S.M. (Shariq ), Roodman, D. (David), Niesvizky, R., Einsele, H. (Hermann), Anderson, K.C. (Kenneth), Dimopoulos, M.A. (Meletios), Avet-Loiseau, H., Mellqvist, U.H. (U. H.), Turesson, I. (I.), Merlini, G. (Giampaolo), Schots, R., McCarthy, P.L. (Philip), Bergsagel, P.L. (Leif), Chim, C.S., Lahuerta, J.J., Shah, J. (Jatin), Reiman, A. (A.), Mikhael, J. (J.), Zweegman, S. (Sonja), Lonial, S. (Sagar), Comenzo, R.L., Chng, W.J. (Wee), Moreau, P., Sonneveld, P. (Pieter), Ludwig, H. (Heinz), Durie, B.G.M. (Brian), San Miguel, J.F. (Jesús Fernando), Ocio, E.M. (E.), Richardson, P.G. (Paul Gerard), Rajkumar, S.V. (Vincent), Palumbo, A. (Antonio), Mateos, M.V., Orlowski, R. (R.), Kumar, S. (Shaji), Usmani, S.M. (Shariq ), Roodman, D. (David), Niesvizky, R., Einsele, H. (Hermann), Anderson, K.C. (Kenneth), Dimopoulos, M.A. (Meletios), Avet-Loiseau, H., Mellqvist, U.H. (U. H.), Turesson, I. (I.), Merlini, G. (Giampaolo), Schots, R., McCarthy, P.L. (Philip), Bergsagel, P.L. (Leif), Chim, C.S., Lahuerta, J.J., Shah, J. (Jatin), Reiman, A. (A.), Mikhael, J. (J.), Zweegman, S. (Sonja), Lonial, S. (Sagar), Comenzo, R.L., Chng, W.J. (Wee), Moreau, P., Sonneveld, P. (Pieter), Ludwig, H. (Heinz), Durie, B.G.M. (Brian), and San Miguel, J.F. (Jesús Fernando)

Abstract

Treatment in medical oncology is gradually shifting from the use of nonspecific chemotherapeutic agents toward an era of novel targeted therapy in which drugs and their combinations target specific aspects of the biology of tumor cells. Multiple myeloma (MM) has become one of the best examples in this regard, reflected in the identification of new pathogenic mechanisms, together with the development of novel drugs that are being explored from the preclinical setting to the early phases of clinical development. We review the biological rationale for the use of the most important new agents for treating MM and summarize their clinical activity in an increasingly busy field. First, we discuss data from already approved and active agents (including second- and third-generation proteasome inhibitors (PIs), immunomodulatory agents and alkylators). Next, we focus on agents with novel mechanisms of action, such as monoclonal antibodies (MoAbs), cell cycle-specific drugs, deacetylase inhibitors, agents acting on the unfolded protein response, signaling transduction pathway inhibitors and kinase inhibitors. Among this plethora of new agents or mechanisms, some are specially promising: anti-CD38 MoAb, such as daratumumab, are the first antibodies with clinical activity as single agents in MM. Moreover, the kinesin spindle protein inhibitor Arry-520 is effective in monotherapy as well as in combination with dexamethasone in heavily pretreated patients. Immunotherapy against MM is also being explored, and probably the most attractive example of this approach is the combination of the anti-CS1 MoAb elotuzumab with lenalidomide and dexamethasone, which has produced exciting results in the relapsed/refractory setting.

Published
2014
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13. The role of vertebral augmentation in multiple myeloma: International Myeloma Working Group Consensus Statement

Author

Hussein, Ma, Vrionis, Fd, Allison, R, Berenson, J, Berven, S, Erdem, E, Giralt, S, Jagannath, S, Kyle, Ra, Legrand, S, Pflugmacher, R, Raje, N, Rajkumar, Sv, Randall, Rl, Roodman, D, Siegel, D, Vescio, R, Zonder, J, Durie, Bg, Alexanian R, International Myeloma Working G. r. o. u. p., Anderson, K, Attal, M, Avet Loiseau, H, Badros, A, Bergsagel, L, Bladé, J, Barlogie, B, Batille, R, Beksac, M, Belch, A, Bensinger, B, Boccadoro, M, Cavo, M, Chen, Wm, Child, T, Chim, J, Comenzo, R, Crowley, J, Dalton, W, Davies, F, de Souza, C, Delforge, M, Dimipoulous, M, Dispenzieri, A, Einsele, H, Facon, T, Fantl, D, Fermand, Jp, Fonseca, R, Gahrton, G, Gertz, M, Gibson, J, Goldschmidt, H, Greipp, P, Hajek, R, Hardan, I, Harousseau, Jl, Hata, H, Hattori, Y, Ho, J, Hungria, V, Hussein, M, Ida, S, Jacobs, P, Jian, H, Joshua, D, Kawano, M, Kumar, S, Kyle, R, Lahuerta, J, Lee, Jh, Lokhorst, H, Ludwig, H, Leleu, X, Maiolino, A, Mehta, J, Merlini, G, Moreau, P, Morgan, G, Munshi, N, Palumbo, Antonio, Pavlovsky, S, Niesvizky, R, Novis, Y, Nouel, A, Powles, R, Pilarski, L, Reece, D, Reiman, T, Richardson, P, Morales, Ar, Sezer, O, Shaughnessy, J, Shimizu, K, Tricot, G, San Miguel, J, Singhal, S, Sonneveld, P, Shustik, C, Spencer, A, Stewart, K, Tosi, P, Turesson, I, Van Ness, B, Van Riet, I, Vesole, D, Waage, A, Wang, M, Weber, D, Westin, J, Wheatley, K, Yehuda, Db, and Zonder, J.

Published
2008

14. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: A report of the International Myeloma Working Group

Author

Kyle, R.A. Child, J.A. Anderson, K. Barlogie, B. Bataille, R. Bensinger, W. Bladé, J. Boccadoro, M. Dalton, W. Dimopoulos, M. Djulbegovic, B. Drayson, M. Durie, B. Facon, T. Fonseca, R. Gahrton, G. Greipp, P. Harousseau, J.L. Harrington, D. Hussein, M. Joshua, D. Ludwig, H. Morgan, G. Oken, M. Powles, R. Richardson, P. Roodman, D. San Miguel, J. Shimizu, K. Shustik, C. Sirohi, B. Sonneveld, P. Tricot, G. Turesson, I. Van Ness, B. Vesole, D. Weber, D. Westin, J. Wheatley, K.

Subjects
immune system diseases, hemic and lymphatic diseases
Abstract

The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/1 and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M-protein is ≥ 30 g/1 and/or bone marrow clonal cells ≥ 10% but no related organ or tissue impairment (ROTI)(end-organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTL Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (± recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.

Published
2003

16. Legumain expression in relation to clinicopathologic and biological variables in colorectal cancer

Author

Murthy, RV, Arbman, G, Gao, Jingfang, Roodman, D, Sun, Xiao-Feng, Murthy, RV, Arbman, G, Gao, Jingfang, Roodman, D, and Sun, Xiao-Feng

Abstract

Purpose: Legumain, a novel asparaginyl endopeptidase, has been observed to be highly expressed in several types of tumors including colorectal cancer. However, there is no study examining the relationship of legumain expression to clinocopatbologic and biological variables in colorectal cancers. Experimental Design: We investigated legumain expression in 164 primary colorectal cancers, 34 corresponding distant normal mucosa samples, 89 adjacent normal mucosa samples, and 33 lymph node metastases using immunohistochemistry. We also did Western blotting analysis on three additional colorectal cancers and three colonic cell lines. Results: Legumain expression was increased in primary tumors compared with distant or adjacent normal mucosa (P < 0.05), but there was no significant change between primary tumors and metastases (P > 0.05). Legumain expression was positively related to poorer differentiation/ mucinous carcinoma (P = 0.04), higher degree of necrosis (P = 0.03) and apoptosis (P < 0.0001), positive proliferating cell nuclear antigen (P < 0.0001) and p53 expression (P = 0.049), and had a positive tendency towards stromelysin 3 (P = 0.058) and PINCH positivity (P = 0.05). The patients with tumors that showed both weak and lower percentage of the legumain expression, either in tumor (P = 0.01) or in stroma (P = 0.04), had a better prognosis. Conclusions: The legumain expression may be involved in colorectal cancer development and have a prognostic value in the patients. ©2005 American Association for Cancer Research.

Published
2005
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19. Society News: Ecological tax reform

Author

Bernow, S., primary, Costanza, R., additional, Daly, H., additional, DeGennaro, R., additional, Erlandson, D., additional, Ferris, D., additional, Hawken, P., additional, Hoerner, J. A., additional, Lancelot, J., additional, Marx, T., additional, Norland, D., additional, Peters, I., additional, Roodman, D., additional, Schneider, C., additional, Shyamsundar, P., additional, and Woodwell, J., additional

Published
1998
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20. Autophagy promotes T-cell survival through degradation of proteins of the cell death machinery.

Author

Kovacs, J R, Li, C, Yang, Q, Li, G, Garcia, I G, Ju, S, Roodman, D G, Windle, J J, Zhang, X, and Lu, B

Subjects
CELL death, T cells, AUTOPHAGY, ENCEPHALOMYELITIS, LYMPHOCYTES
Abstract

Autophagy is implicated in regulating cell death in activated T cells, but the underlying mechanism is unclear. Here, we show that inhibition of autophagy via Beclin 1 gene deletion in T cells leads to rampant apoptosis in these cells upon TCR stimulation. Beclin 1-deficient mice fail to mount autoreactive T-cell responses and are resistant to experimental autoimmune encephalomyelitis. Compared with Th17 cells, Th1 cells are much more susceptible to cell death upon Beclin 1 deletion. Cell death proteins are highly increased in Beclin 1-deficient T cells and inhibition of caspases and genetic deletion of Bim reverse apoptosis. In addition, p62/sequestosome 1 binds to caspase-8 but does not control levels of procaspase-8 or other cell death-related proteins. These results establish a direct role of autophagy in inhibiting the programmed cell death through degradation of apoptosis proteins in activated T cells. [ABSTRACT FROM AUTHOR]

Published
2012
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23. The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group

Author

E, Terpos, M A, Dimopoulos, O, Sezer, D, Roodman, N, Abildgaard, R, Vescio, P, Tosi, R, Garcia-Sanz, F, Davies, A, Chanan-Khan, A, Palumbo, P, Sonneveld, M T, Drake, J-L, Harousseau, K C, Anderson, B G M, Durie, Jeffrey, Zonder, Terpos E, Dimopoulos MA, Sezer O, Roodman D, Abildgaard N, Vescio R, Tosi P, Garcia-Sanz R, Davies F, Chanan-Khan A, Palumbo A, Sonneveld P, Drake MT, Harousseau JL, Anderson KC, Durie BG, Radiology & Nuclear Medicine, and Hematology

Subjects
Cancer Research, medicine.medical_specialty, Pathology, Osteolysis, Bone disease, Bone resorption, Bone remodeling, N-terminal telopeptide, Internal medicine, Medicine, Humans, BIOCHEMICAL MARKERS, Multiple myeloma, Hematology, business.industry, Ossification, International Agencies, International Myeloma Working Group, medicine.disease, Oncology, Biological Markers, Bone Remodeling, medicine.symptom, business, Multiple Myeloma, Biomarkers
Abstract

Lytic bone disease is a frequent complication of multiple myeloma (MM). Lytic lesions rarely heal and X-rays are of limited value in monitoring bone destruction during anti-myeloma or anti-resorptive treatment. Biochemical markers of bone resorption (amino-and carboxy-terminal cross-linking telopeptide of type I collagen (NTX and CTX, respectively) or CTX generated by matrix metalloproteinases (ICTP)) and bone formation provide information on bone dynamics and reflect disease activity in bone. These markers have been investigated as tools for evaluating the extent of bone disease, risk of skeletal morbidity and response to anti-resorptive treatment in MM. Urinary NTX, serum CTX and serum ICTP are elevated in myeloma patients with osteolytic lesions and correlate with advanced disease stage. Furthermore, urinary NTX and serum ICTP correlate with risk for skeletal complications, disease progression and overall survival. Bone markers have also been used for the early diagnosis of bone lesions. This International Myeloma Working Group report summarizes the existing data for the role of bone markers in assessing the extent of MM bone disease and in monitoring bone turnover during anti-myeloma therapies and provides information on novel markers that may be of particular interest in the near future. Leukemia (2010) 24, 1700-1712; doi:10.1038/leu.2010.173; published online 2 September 2010

Published
2010

25. Bones in Multiple Myeloma: Imaging and Therapy.

Author

Zamagni E, Cavo M, Fakhri B, Vij R, and Roodman D

Subjects
Bone and Bones pathology, Humans, Multiple Myeloma pathology, Bone and Bones diagnostic imaging, Multiple Myeloma diagnostic imaging
Abstract

Bone disease is the most frequent disease-defining clinical feature of multiple myeloma (MM), with 90% of patients developing bone lesions over the course of their disease. For this reason, imaging plays a major role in the management of disease in patients with MM. Although conventional radiography has traditionally been the standard of care, its low sensitivity in detecting osteolytic lesions has called for more advanced imaging modalities. In this review, we discuss the advantages, indications, and applications of whole-body low-dose CT (WBLDCT), 18 F-fluorodeoxyglucose (FDG)-PET/CT, MRI, and other novel imaging modalities in the management of disease in patients with plasma cell dyscrasias. We also review the state of the art in treatment of MM bone disease (MMBD) and the role of bisphosphonates and denosumab, a monoclonal antibody that binds and blocks the activity of receptor activator of nuclear factor-kappa B ligand (RANKL), which was recently approved by the U.S. Food and Drug Administration for MMBD.

Published
2018
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28. MIP-1alpha (CCL3) is a downstream target of FGFR3 and RAS-MAPK signaling in multiple myeloma.

Author

Masih-Khan E, Trudel S, Heise C, Li Z, Paterson J, Nadeem V, Wei E, Roodman D, Claudio JO, Bergsagel PL, and Stewart AK

Subjects
Bone Diseases etiology, Chemokine CCL3, Chemokine CCL4, Enzyme Inhibitors pharmacology, Gene Expression Regulation, Neoplastic drug effects, Humans, Macrophage Inflammatory Proteins genetics, Multiple Myeloma complications, Multiple Myeloma genetics, Mutation, Neoplasm Proteins, RNA, Small Interfering pharmacology, Receptor, Fibroblast Growth Factor, Type 3 antagonists & inhibitors, Receptor, Fibroblast Growth Factor, Type 3 physiology, Tumor Cells, Cultured, ras Proteins genetics, MAP Kinase Signaling System physiology, Macrophage Inflammatory Proteins metabolism, Multiple Myeloma etiology, Receptor, Fibroblast Growth Factor, Type 3 genetics, ras Proteins metabolism
Abstract

Overexpression of fibroblast growth factor receptor 3 (FGFR3) is a hallmark of t(4;14) multiple myeloma (MM). To dissect the mechanism of FGFR3 oncogenesis in MM, we used 3 FGFR selective kinase inhibitors-CHIR258, PD173074, and SU5402-and FGFR3-specific siRNA to modulate FGFR3 activity. Conversely, the ligand FGF was used to stimulate FGFR3 function in human MM cells. The transcriptional response to FGFR3 modification was recorded, and gene expression changes common to all 5 modifiers were documented. Ten genes were commonly regulated. Macrophage inflammatory protein-1 alpha (MIP-1alpha) was the single most differentially altered gene. MIP-1 alpha promoter function, gene expression, and protein secretion were each down-regulated following inhibition of FGFR3 signaling. Down-regulation of MIP-1 alpha was not, however, observed following FGFR3 inhibition in MM cells with RAS mutations implicating RAS-MAPK in MIP-1 alpha regulation. As confirmation, inhibition of ERK1 also down-regulated MIP-1 alpha in FGFR3 inhibitor-resistant cells harboring RAS mutations. MIP-1 alpha is implicated in the survival and proliferation of MM cells and the pathogenesis of MM bone disease. 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.

Published
2006
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29. Thalidomide derivative CC-4047 inhibits osteoclast formation by down-regulation of PU.1.

Author

Anderson G, Gries M, Kurihara N, Honjo T, Anderson J, Donnenberg V, Donnenberg A, Ghobrial I, Mapara MY, Stirling D, Roodman D, and Lentzsch S

Subjects
Angiogenesis Inhibitors adverse effects, Angiogenesis Inhibitors therapeutic use, Bone Resorption drug therapy, Bone Resorption metabolism, Cell Differentiation physiology, Cells, Cultured, Dose-Response Relationship, Drug, Down-Regulation drug effects, Down-Regulation physiology, Humans, Macrophage Colony-Stimulating Factor pharmacology, Multiple Myeloma drug therapy, Myeloid Progenitor Cells cytology, NF-kappa B antagonists & inhibitors, NF-kappa B metabolism, Osteoclasts cytology, Thalidomide adverse effects, Thalidomide pharmacology, Thalidomide therapeutic use, Angiogenesis Inhibitors pharmacology, Cell Differentiation drug effects, Myeloid Progenitor Cells metabolism, Osteoclasts metabolism, Proto-Oncogene Proteins biosynthesis, Thalidomide analogs & derivatives, Trans-Activators biosynthesis
Abstract

CC-4047, an immunomodulatory analog of thalidomide, inhibits multiple myeloma with unknown effects on the human osteoclast lineage. Early osteoclast progenitors are of hematopoietic origin and differentiate into mature bone resorbing multinucleated osteoclasts. We investigated the effects of CC-4047 and thalidomide on human osteoclastogenesis, using in vitro receptor activator of NFkappa-B ligand/macrophage colony-stimulating factor-stimulated bone marrow cell cultures. Treating bone marrow cultures with CC-4047 for 3 weeks decreased osteoclast formation accompanied by complete inhibition of bone resorption. The inhibitory effect was similar when cultures were treated for 3 weeks or for only the first week (90% inhibition), indicating that CC-4047 inhibits early stages of osteoclast formation. Inhibition of osteoclastogenesis by CC-4047 was mediated by a shift of lineage commitment to granulocyte colony-forming units at the expense of granulocyte-macrophage colony-forming units. Further studies revealed that this shift in lineage commitment was mediated through down-regulation of PU.1. Treatment with thalidomide resulted in significantly less potent inhibition of osteoclast formation and bone resorption. These results provide evidence that CC-4047 blocks osteoclast differentiation during early phases of osteoclastogenesis. Therefore, CC-4047 might be a valuable drug for targeting both tumors and osteoclastic activity in patients with multiple myeloma and other diseases associated with osteolytic lesions.

Published
2006
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30. Mechanisms of tumor metastasis to the bone: challenges and opportunities.

Author

Reddi AH, Roodman D, Freeman C, and Mohla S

Subjects
Animals, Bone Morphogenetic Proteins metabolism, Breast Neoplasms pathology, Extracellular Matrix metabolism, Female, Humans, Male, Models, Biological, Multiple Myeloma pathology, Osteoblasts metabolism, Osteoclasts metabolism, Parathyroid Hormone metabolism, Prostatic Neoplasms pathology, Bone Neoplasms secondary, Neoplasm Metastasis
Abstract

In human cancers, bone is a common site for metastasis. It is well known that metastasis is the cause of morbidity and mortality in patients with cancer. Both breast and prostate carcinomas have a propensity to metastasize to bone. In general, metastatic breast cancers result in osteolytic lesions. On the other hand, prostate cancer metastases are osteoblastic and result in osteosclerosis. Thus, bone formation and bone resorption are at the crux of the cancer metastasis problem. For example, in the prostate, there is a vicious cycle of metastasis to bone (Fig. 1). Metastases to bone causes excruciating bone pain, pathological fractures, and eventually death, and therefore is a serious challenge to both bone biologists and cancer cell biologists. The stromal-epithelial interactions in breast and prostate are critical in initiation of carcinogenesis and the progression of the metastatic cascade to bone (Fig. 2). Over a hundred years ago, Stephen Paget enunciated the seed and soil hypothesis in which seeds of metastatic cancer cells of breast preferentially settle in the soil of bone matrix. Thus, the prostate/breast cancer bone interface and continuum has continuously presented challenges and opportunities and were discussed at a recent workshop.

Published
2003
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31. Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation.

Author

Durie BG, Kyle RA, Belch A, Bensinger W, Blade J, Boccadoro M, Child JA, Comenzo R, Djulbegovic B, Fantl D, Gahrton G, Harousseau JL, Hungria V, Joshua D, Ludwig H, Mehta J, Morales AR, Morgan G, Nouel A, Oken M, Powles R, Roodman D, San Miguel J, Shimizu K, Singhal S, Sirohi B, Sonneveld P, Tricot G, and Van Ness B

Subjects
Anemia etiology, Anemia therapy, Antineoplastic Agents standards, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols standards, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Diseases etiology, Bone Diseases therapy, Diagnosis, Differential, Humans, Kidney Diseases etiology, Kidney Diseases therapy, Multiple Myeloma complications, Multiple Myeloma diagnosis, Multiple Myeloma mortality, Quality Assurance, Health Care, Stem Cell Transplantation standards, Survival Analysis, Multiple Myeloma therapy
Abstract

These consensus guidelines have been compiled with input from the Scientific Advisors of the International Myeloma Foundation. Their production involved several steps including: A 3-day Scientific Advisors meeting, during which each specific area was presented and discussed (May 2002). Review of key literature, especially randomized study results, but also Medline, Internet, Cochrane database searches, and prior guidelines (Br J Haematol 115: 522-540, 2001). Feedback from patients participating in the International Myeloma Foundation, patient programs. These guidelines encompass both the published literature and expert opinions. Recommendations based upon expert opinions are identified as such. The intent is for the guidelines to be international in scope, plus provide recommendations for both clinical practice and research approaches. 'Consensus' reflects general, although not necessarily unanimous, agreement. Details are discussed as appropriate. For convenience, the recommendations are divided into: 1. Diagnostic criteria. 2. Staging and prognostic factors. 3. Frontline therapy. 4. High-dose therapy and transplant. 5. Maintenance therapy. 6. Supportive care and management of specific complications. 7. Novel therapies and new technologies.

Published
2003

32. Fighting pollution in Viet Nam.

Author

Roodman DM

Subjects
Asia, Asia, Southeastern, Developing Countries, Economics, Environment, Organization and Administration, Vietnam, Community Participation, Environmental Pollution, Public Sector, Research, Social Welfare
Published
1999

33. Cadherin-6 mediates the heterotypic interactions between the hemopoietic osteoclast cell lineage and stromal cells in a murine model of osteoclast differentiation.

Author

Mbalaviele G, Nishimura R, Myoi A, Niewolna M, Reddy SV, Chen D, Feng J, Roodman D, Mundy GR, and Yoneda T

Subjects
Amino Acid Sequence, Animals, Base Sequence, Cadherins genetics, Cadherins metabolism, Cell Differentiation, Cells, Cultured, Cloning, Molecular, DNA, Complementary, Gene Expression, Hematopoiesis, Humans, Mice, Models, Biological, Molecular Sequence Data, Oligonucleotides, Antisense, Protein Conformation, RNA, Messenger, Sequence Homology, Amino Acid, Cadherins physiology, Osteoclasts metabolism, Stromal Cells metabolism
Abstract

Osteoclasts are multinucleated cells of hemopoietic origin that are responsible for bone resorption during physiological bone remodeling and in a variety of bone diseases. Osteoclast development requires direct heterotypic cell-cell interactions of the hemopoietic osteoclast precursors with the neighboring osteoblast/stromal cells. However, the molecular mechanisms underlying these heterotypic interactions are poorly understood. We isolated cadherin-6 isoform, denoted cadherin-6/2 from a cDNA library of human osteoclast-like cells. The isolated cadherin-6/2 is 3,423 bp in size consisting of an open reading frame of 2,115 bp, which encodes 705 amino acids. This isoform lacks 85 amino acids between positions 333 and 418 and contains 9 different amino acids in the extracellular domain compared with the previously described cadherin-6. The human osteoclast-like cells also expressed another isoform denoted cadherin-6/1 together with the cadherin-6. Introduction of cadherin-6/2 into L-cells that showed no cell-cell contact caused evident morphological changes accompanied with tight cell-cell association, indicating the cadherin-6/2 we isolated here is functional. Moreover, expression of dominant-negative or antisense cadherin-6/2 construct in bone marrow-derived mouse stromal ST2 cells, which express only cadherin-6/2, markedly impaired their ability to support osteoclast formation in a mouse coculture model of osteoclastogenesis. Our results suggest that cadherin-6 may be a contributory molecule to the heterotypic interactions between the hemopoietic osteoclast cell lineage and osteoblast/bone marrow stromal cells required for the osteoclast differentiation. Since both osteoclasts and osteoblasts/bone marrow stromal cells are the primary cells controlling physiological bone remodeling, expression of cadherin-6 isoforms in these two cell types of different origin suggests a critical role of these molecules in the relationship of osteoclast precursors and cells of osteoblastic lineage within the bone microenvironment.

Published
1998
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