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July 30, 2002 IMF Myeloma Minute


07.31.02

In the News:

What's New in Myeloma Research:

  • International Myeloma Foundation and Goldman Philanthropic Partnerships Cosponsor New Research Initiative
    It's the Inspired Venture Program in Multiple Myeloma, a new opportunity for donors to target their funding for groundbreaking myeloma research. Based on venture capital and limited partnerships, this new program brings together foundations, research institutions, the business community, and individual donors to advance breakthrough research.
  • Manumycin inhibits farnesyltransferase and induces apoptosis of drug-resistant interleukin 6-producing myeloma cells
    Maria Antonia Frassanito, Antonio Cusmai, Claudia Piccoli and Franco Dammacco
    British Journal of Haematology Volume 118 Issue 1 Page 157 - July 2002

    Summary: Interleukin 6 (IL-6) is an important survival and growth factor for myeloma cells and exerts its effects by activating several transduction pathways, including the Ras cascade. As farnesylation of the activated Ras oncogene product by protein farnesyltransferase (FTase) is a critical step for Ras functional activity, FTase has emerged as a potential target for the development of new anti-cancer agents. Based on our previous demonstration that IL-6-producing myeloma cells are refractory to drug-induced apoptosis, we have analysed the effect of manumycin, a natural FTase inhibitor, on IL-6-producing myeloma cells resistant to Fas-, dexamethasone- and doxorubicin-induced apoptosis. Treatment of myeloma cells with manumycin prevented cell proliferation and induced apoptosis. Western blotting experiments demonstrated that this effect was related to inhibition of the post-translational Ras processing.Further analysis showed that manumycin-induced apoptosis involved caspase-3. Activation of caspase-3, in fact, was observed in 6h-treated myeloma cells expressing Apo 2·7 antigen, the marker of early apoptosis, whereas their treatment with cell-permeable DEVD-fmk, that irreversibly inhibits caspase-3 activity, prevented their apoptosis. Over-expression of caspase-3 was also demonstrated by reverse transcription-polymerase chain reaction. Finally, over-expression of Bcl-2 and its homologue Bcl-xL was observed in manumycin-treated cells as well as in control myeloma cells, implying that the Bcl-2 family is not involved. FTase inhibitors may thus be proposed as a potential pharmacological weapon, as they block the Ras pathway and induce the apoptosis of drug-resistant IL-6-producing myeloma cells.
  • Pamidronate induces bone formation in patients with smouldering or indolent myeloma, with no significant anti-tumour effect
    Alejandro Martín1, Ramón García-Sanz1, José Hernández2, Joan Bladé3, Begoña Suquía1, Javier Fernández-Calvo4, Marcos González1, Gema Mateo5, Alberto Orfao5 and Jesus F. San Miguel1
    British Journal of Haematology Volume 118 Issue 1 Page 239 - July 2002

    Summary: Twelve patients with smouldering or indolent multiple myeloma (MM) received 12 courses of intravenous pamidronate as a single agent to evaluate both the antitumour and bone metabolism effects. One patient achieved minor response, eight had stable disease, and three - all indolent MM - showed disease progression. Serum interleukin 6 (IL-6), IL-1 and Oncostatin-M remained stable throughout the study, while tumour necrosis factor- increased. Bone density significantly increased after four and 12 courses compared with baseline. Markers for bone resorption and bone formation decreased with treatment. These results suggest that pamidronate treatment reduces bone turnover in smouldering or indolent MM, but has no significant antitumour effect.

Items of Interest:
  • Thalidomide, Statins, And Angiomax
    Data presented this week support two of Celgene's products - the thalidomide analog Actimid for multiple myeloma, and thalidomide itself for a new indication, ankylosing spondylitis.

Important Dates to Remember:

Novel Therapies and New Technologies
Toronto & Districts Multiple Myeloma Support Group Meeting Sponsored by Ortho Biotech
August 15th

IMF Patient & Family Seminar: Chicago, IL
August 16th and 17th

International Myeloma Foundation Multiple Myeloma Awareness Week
August 26th - September 1st

Ribbon of Hope: Making A World of Difference 12th Anniversary Gala
Washington D.C.
October 5th

IMF Patient & Family Seminar: Seattle, WA
November 8th and 9th


Clinical Trials:

Melphalan, Total-Body Irradiation, and Peripheral Stem Cell Transplantation Compared With Combination Chemotherapy in Treating Patients With Previously Untreated Multiple Myeloma.

Combination Chemotherapy With or Without Interferon alfa in Treating Patients With Previously Untreated Multiple Myeloma.

Combination Chemotherapy in Treating Patients With Multiple Myeloma.

Conditioning Therapy and Blood or Marrow Transplantation in Patients With Severe Hematologic Malignancy.

Epoetin Alfa in Patients With Multiple Myeloma and Chemotherapy Related Anemia.

Three Regimens For the Prevention of Delayed Nausea After Chemotherapy in Patients With Chemotherapy-Naive Cancer.


Exciting Opportunities:

Multiple Myeloma Quilt of Courage
All the squares for the first quilt have been sold! We are now taking orders for the second quilt. Deadline will be September 27th.


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