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Differentiation induction of blast cells in two cases of childhood acute megakaryoblastic leukemia in vitro by interleukin-3 and interleukin-6: an ultrastructural cytochemical study.

Abstract
Although hematopoietic growth factors influence renewal and differentiation of blast progenitors in acute myelogenous leukemia (AML), morphological maturation of leukemic blasts is thought a rare event, even when cultured in the presence of appropriate growth stimulants. However, light microscopic observation may not be sufficient to clarify precisely the effects of hematopoietic growth factors on the morphological differentiation of leukemic blasts. In this study, using cell culture techniques and electron microscopic cytochemistry for platelet peroxidase (PPO), we studied the effects of interleukin-3 (IL-3) and interleukin-6 (IL-6), both of which are considered to play an important role in normal megakaryocytopoiesis, on the growth and differentiation of blast cells from two patients with childhood acute megakaryoblastic leukemia (AMKL). In both of the two cases, IL-3 stimulated leukemic colony formation in methylcellulose culture, whereas IL-6 showed little such activity. However, in suspension culture, IL-6 was active in promoting megakaryocytic differentiation, although incomplete, as detected by increase in the number of PPO-positive cells, some having demarcation membrane-like structure. This effect was evident in culture with IL-6 alone in one patient, but it was detectable only when IL-6 was used in combination with IL-3 in the other patient. In contrast, IL-3 alone stimulated differentiation towards myeloid but not megakaryocytic lineage. These results indicate that IL-3 and IL-6 have a distinct role in leukemic megakaryocytopoiesis (IL-3 stimulates growth, whereas IL-6 promotes morphological differentiation) and that cooperation between these two cytokines functions most effectively for megakaryocytic differentiation of AMKL cells in a fashion similar to that for normal megakaryocytopoiesis.
AuthorsJ Miyauchi, K Sugita, M Okui, N Taguchi, S C Clark, K Shimizu
JournalJournal of cellular physiology (J Cell Physiol) Vol. 148 Issue 3 Pg. 404-13 (Sep 1991) ISSN: 0021-9541 [Print] United States
PMID1655816 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Interleukin-3
  • Interleukin-6
  • Recombinant Proteins
  • Peroxidases
  • Peroxidase
Topics
  • Blast Crisis (pathology)
  • Bone Marrow (pathology)
  • Cell Differentiation (drug effects)
  • Cell Division (drug effects)
  • Cells, Cultured
  • Cytoplasmic Granules (enzymology, ultrastructure)
  • Female
  • Golgi Apparatus (ultrastructure)
  • Humans
  • Infant
  • Interleukin-3 (pharmacology)
  • Interleukin-6 (pharmacology)
  • Leukemia, Megakaryoblastic, Acute (pathology)
  • Microscopy, Electron
  • Peroxidase (blood)
  • Peroxidases (blood)
  • Recombinant Proteins (pharmacology)

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