Hi Trey, I am afraid you are wrong. Doctors are NOT talking about suppression of the immune system like in low WBC when they talk about Gleevec and the immune system. They are talking about Gleevec inhibiting the proliferation of the T-cell lymphocytes, which are part of our immune system. Not enough are being produced according to lab studies. There are lots of studies done on this right from 2003 with some doctors finding a compromise and others not. Please see below. I subscribe to Leukemia so I have read the ones not having abstracts. I agree that we do not have to be afraid all the time since these are lab studies and not totally validated but the studies have been done by CML experts from MDACC and other places. If we do not have enough of the T cells like these doctors are proving from lab studies, it is not suppression but a compromise of the immune system.
Obviously, the compromise is not to the extent that you have to live in a bubble but data is data. And also remember what is found in the lab may not necessarily mimic in humans. However, quite a few patients on Gleevec have got shingles. Please do post any of the articles you mentioned, do they talk about Gleevec's effect on the immune system or Gleevec suppressing the marrow? Both are different. This all helps in our learning, including yours :-) ~Anjana 1: Leukemia. 2006 Jan;20(1):142-3. Links Imatinib does not impair specific antitumor T-cell immunity in patients with chronic myeloid leukemia. Bocchia M, Abruzzese E, Forconi F, Ippoliti M, Trawinska MM, Pirrotta MT, Raspadori D, Tozzi M, Gozzetti A, Lauria F. Leukemia. 2005 Nov;19(11):1905-11. Links Imatinib mesylate suppresses cytokine synthesis by activated CD4 T cells of patients with chronic myelogenous leukemia. Gao H, Lee BN, Talpaz M, Donato NJ, Cortes JE, Kantarjian HM, Reuben JM. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Although imatinib mesylate (IM) is highly effective at inducing complete cytogenetic remission in patients with chronic myelogenous leukemia (CML), it is known to suppress T-cell proliferation in vitro. As cytokines are required for T-cell proliferation, we investigated the effects of IM on cytokine synthesis by T cells of CML patients by assessing cytokine synthesis by activated CD4+ and CD8+ T cells in vitro. The activation of T cells in the whole blood of IM-treated patients (CML-IM) with Staphylococcus enterotoxin B resulted in significantly lower percentages of CD4+ T cells that synthesized interleukin 2 (P = 0.017), interferon-gamma (P = 0.010), and tumor necrosis factor-alpha (P = 0.009) than did the activated T cells of control subjects. The addition of exogenous IM to the cultures of peripheral blood mononuclear cells of CML-IM patients reduced Th1 cytokine synthesis by the CD4+ T cells. Furthermore, IM therapy at clinical doses suppressed the tyrosine phosphorylation of ZAP70. These findings suggest that inhibition of ZAP70 signaling pathway and suppression of Th1 cytokine synthesis by CD4+ T cells required the presence of IM at the time of T-cell activation through the T-cell receptor. Leukemia. 2004 Aug;18(8):1332-9. Links Comment in: Leukemia. 2005 Mar;19(3):456-7; author reply 457. Imatinib inhibits the activation and proliferation of normal T lymphocytes in vitro. Cwynarski K, Laylor R, Macchiarulo E, Goldman J, Lombardi G, Melo JV, Dazzi F. Department of Immunology, Division of Medicine, Faculty of Medicine, Imperial College at Hammersmith Hospital, London, UK. The ABL tyrosine kinase inhibitor imatinib mesylate is highly effective in the treatment of CML and is increasingly used in the stem cell transplantation (SCT) setting. Since ABL-dependent intracellular signaling molecules are involved in T-cell activation, imatinib may affect T-cell responses in vivo, thus affecting T-cell function in CML patients, disrupting immune reconstitution after allogeneic SCT and/or impeding the graft-versus-leukemia effect. Here we demonstrate that imatinib inhibits PHA-induced proliferation of normal peripheral blood mononuclear cells at in vitro concentrations (1-5 micromol/l) representative of the pharmacological doses used therapeutically in vivo. The effect is not dependent on antigen-presenting cells because CD3/CD28-induced T-cell stimulation was similarly inhibited by imatinib. Dose-dependent inhibition of the proliferative response of purified CD8+ and CD4+ T lymphocytes to anti-CD3/CD28 was similarly observed and associated with reduction in IFN-gamma production. The inhibitory effect could not be ascribed to an increased rate of apoptosis but the expression of activation markers on CD3+ T cells was significantly reduced in the presence of imatinib (1-5 micromol/L). Inhibition of T-cell proliferation was reversible after removal of the drug from the cultures. Thus, imatinib inhibits T-cell proliferation in vitro, an effect that is APC-independent, reversible, and does not involve apoptosis induction. Blood. 2004 Aug 15;104(4):1094-9. Epub 2004 Apr 20. Links Imatinib mesylate inhibits T-cell proliferation in vitro and delayed-type hypersensitivity in vivo. Dietz AB, Souan L, Knutson GJ, Bulur PA, Litzow MR, Vuk-Pavlovic S. Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. [EMAIL PROTECTED] Imatinib mesylate (STI571, imatinib) inhibited DNA synthesis in primary human T cells stimulated with allogeneic mature dendritic cells or phytohemagglutinin (PHA) but did not induce apoptosis. The values for the concentration that inhibits 50% (IC50) of T-cell proliferation stimulated by dendritic cells and PHA were 3.9 microM and 2.9 microM, respectively, that is, within the concentration range found in patients treated with imatinib mesylate. Interestingly, imatinib mesylate did not inhibit expression of T-cell activation markers CD25 and CD69, although it reduced the levels of activated nuclear factor-kappaB (NF-kappaB) and changed phosphorylation or protein levels of Lck, ERK1/2, retinoblastoma protein, and cyclin D3. When T cells were washed free of imatinib mesylate, they proliferated in response to PHA, demonstrating that inhibition is reversible. Treatment with imatinib mesylate led to accumulation of the cells in G0/G1 phase of the cell cycle. The in vitro observations were confirmed in vivo in a murine model of delayed-type hypersensitivity (DTH). In mice treated with imatinib mesylate, DTH was reduced in comparison to sham-injected controls. However, the number of splenic T cells was not reduced showing that, similarly to in vitro observations, imatinib mesylate inhibited T-cell response, but did not cause apoptosis. These findings indicate that long-term administration of high-dose imatinib mesylate might affect immunity. Leukemia. 2003 Sep;17(9):1713-21. Links Imatinib inhibits the in vitro development of the monocyte/macrophage lineage from normal human bone marrow progenitors. Dewar AL, Domaschenz RM, Doherty KV, Hughes TP, Lyons AB. Division of Haematology, Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia. The antileukaemic tyrosine kinase inhibitor, imatinib, has been reported to inhibit specifically the growth of bcr-abl expressing CML progenitors at levels of 0.1-5.0 microM, by blocking the ATP-binding site of the kinase domain of bcr-abl. Inhibition of the c-abl, platelet-derived growth factor receptor and stem cell factor receptor (c-kit) tyrosine kinases by imatinib has also been reported. Here, we demonstrate that imatinib significantly inhibits in vitro monocyte/macrophage development from normal bone marrow progenitors, while neutrophil and eosinophil development was less affected. Monocyte/macrophage inhibition was observed in semisolid agar and liquid cultures at concentrations of imatinib as low as 0.3 microM. The maturation of monocytes into macrophages was also found to be impaired following treatment of cultures with 1.0 microM imatinib. Imatinib blocked monocyte/macrophage development in cultures stimulated with and without M-CSF, suggesting that inhibition of the M-CSF receptor, c-fms, by imatinib was unlikely to be responsible. Imatinib may therefore have an inhibitory activity for other kinase(s) that play a role in monocyte/macrophage differentiation. This inhibition of normal monocyte/macrophage development was observed at concentrations of imatinib achievable pharmacologically, suggesting that imatinib or closely related derivatives may have potential for the treatment of diseases where monocytes/macrophages contribute to pathogenesis. --~--~---------~--~----~------------~-------~--~----~ [CMLHope] A support group of http://cmlhope.com ------------------------------------------------- You received this message because you are subscribed to the Google Groups "CMLHope" group. 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