Tags

Type your tag names separated by a space and hit enter

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.CC

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.

Authors+Show Affiliations

Department of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. jreuben@mdanderson.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10815885

Citation

Reuben, J M., et al. "Restoration of Th1 Cytokine Synthesis By T Cells of Patients With Chronic Myelogenous Leukemia in Cytogenetic and Hematologic Remission With Interferon-alpha." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 6, no. 5, 2000, pp. 1671-7.
Reuben JM, Lee BN, Johnson H, et al. 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;6(5):1671-7.
Reuben, J. M., Lee, B. N., Johnson, H., Fritsche, H., Kantarjian, H. M., & Talpaz, M. (2000). Restoration of Th1 cytokine synthesis by T cells of patients with chronic myelogenous leukemia in cytogenetic and hematologic remission with interferon-alpha. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 6(5), 1671-7.
Reuben JM, et al. 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;6(5):1671-7. PubMed PMID: 10815885.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Restoration of Th1 cytokine synthesis by T cells of patients with chronic myelogenous leukemia in cytogenetic and hematologic remission with interferon-alpha. AU - Reuben,J M, AU - Lee,B N, AU - Johnson,H, AU - Fritsche,H, AU - Kantarjian,H M, AU - Talpaz,M, PY - 2000/5/18/pubmed PY - 2000/9/2/medline PY - 2000/5/18/entrez SP - 1671 EP - 7 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 6 IS - 5 N2 - 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. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/10815885/Restoration_of_Th1_cytokine_synthesis_by_T_cells_of_patients_with_chronic_myelogenous_leukemia_in_cytogenetic_and_hematologic_remission_with_interferon_alpha_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=10815885 DB - PRIME DP - Unbound Medicine ER -