Restoration of Th1 cytokine synthesis by T cells of patients with chronic myelogenous leukemia in cytogenetic and hematologic remission with interferon-alpha. NLM AIDSLINE Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Click here to return to AIDSLINE main menu
DonateNow
Print this Article


Restoration of Th1 cytokine synthesis by T cells of patients with chronic myelogenous leukemia in cytogenetic and hematologic remission with interferon-alpha.

Clin Cancer Res. 2000 May;6(5):1671-7. Unique Identifier : AIDSLINE MED/20273332
Reuben JM; Lee BN; Johnson H; Fritsche H; Kantarjian HM; Talpaz M; Department of Laboratory Medicine, The University of Texas M.D.; Anderson Cancer Center, Houston 77030, USA.; jreuben@mdanderson.org


Abstract: Chronic myelogenous leukemia (CML) is a disorder of the hematopoietic stem cell that results in malignant expansion of myeloid cells with a cytogenetic abnormality, the translocation between chromosomes 9 and 22 known as the Philadelphia chromosome. Treatment with IFN-alpha has proven to be an effective therapy, inducing cytogenetic remission in CML patients. However, it is unknown whether IFN-alpha can restore normal immune function for patients who achieve a complete cytogenetic remission. To address this question, we used a method of intracellular staining and flow cytometric analysis to ascribe the syntheses of Th1 or Th2 cytokines to T-cell subsets of patients in chronic, in accelerated, and in blast crisis phases as well as patients who had achieved a complete cytogenetic remission with IFN-alpha. We assessed the cytoplasmic synthesis of cytokine in phorbol ester (phorbol 12-myristate 13-acetate)-activated CD4+ and CD8+ T-cell subsets of 81 patients with various stages of CML and 21 normal controls. The percentages of CD4+ and CD8+ T cells from patients in chronic, in accelerated, and in blast crisis phases that synthesized Th1 cytokines interleukin (IL)-2, IFN-gamma, and tumor necrosis factor-alpha were significantly lower than those of remission patients and normal controls. Conversely, the percentages of CD4+ and CD8+ T cells of patients in chronic, in accelerated, and in blast crisis phases of CML preferentially synthesized the Th2 cytokine IL-10. Patients who achieved a durable complete cytogenetic remission for >2 years without maintenance IFN-alpha therapy restored their preference for a Th1 cytokine profile that is necessary for efficient cytotoxic T-cell function.


Keywords: JOURNAL ARTICLE Antineoplastic Agents/*THERAPEUTIC USE Cytokines/*BIOSYNTHESIS CD8-Positive T-Lymphocytes/DRUG EFFECTS/METABOLISM Flow Cytometry Human Interferon Type II/BIOSYNTHESIS Interferon-alpha/*THERAPEUTIC USE Interleukin-10/BIOSYNTHESIS Interleukin-2/BIOSYNTHESIS Leukemia, Myeloid, Chronic/*BLOOD/DRUG THERAPY Lymphocyte Transformation/DRUG EFFECTS Remission Induction T-Lymphocytes/DRUG EFFECTS/*METABOLISM Tetradecanoylphorbol Acetate/PHARMACOLOGY Th1 Cells/METABOLISM Tumor Necrosis Factor/BIOSYNTHESIS

KWDjournalarticleantineoplasticagents/KWDtherapeuticusecytokines/KWDbiosynthesiscd8-positivet-lymphocytes/drugeffects/metabolismflowcytometryhumaninterferontypeii/biosynthesisinterferon-alpha/KWDtherapeuticuseinterleukin-10/biosynthesisinterleukin-2/biosynthesisleukemia,myeloid,chronic/KWDblood/drugtherapylymphocytetransformation/drugeffectsremissioninductiont-lymphocytes/drugeffects/KWDmetabolismtetradecanoylphorbolacetate/pharmacologyth1cells/metabolismtumornecrosisfactor/biosynthesis
001130
A00B1181


Copyright © 2000 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Elton John AIDS Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2000. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2000. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .