Abnormal granulocyte feedback regulation of colony forming and colony stimulating activity-producing cells from patients with chronic myelogenous leukemia

Hal E. Broxmeyer, Naomi Mendelsohn, Malcolm A.S. Moore

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Colony inhibiting activity (CIA), which can be obtained from human polymorphonuclear neutrophil leukocytes (PMN), reduces the numbers of bone marrow and blood (density < 1.070 g/cm3) cells which can spontaneously proliferate in vitro to form colonies and clusters. However, PMN from patients with chronic myelogenous leukemia (CML) were quantitatively deficient in CIA regardless of the patient's clinical status or in vitro growth patterns. Even greater differences in (CIA) between normal and CML-PMN were unmasked by high speed centrifugation of PMN-extracts. Potency of CIA from normal PMN could be enhanced by removal of material pelleted after centrifugation at 160,000 g. Removal of the pellet also decreased the 37°C temperature sensitivity of CIA. CIA from CML-PMN was not enhanced by this procedure. CIA obtained from CML-PMN had the same site of action as that from normal PMN. Although not species specific, CML-CIA was specific in its non-toxic action on the Colony Stimulating Activity (CSA)-producing cell; both CFU-c and cell-free CSA molecules were not affected. A further defect was noted in that target cells (density < 1.070 g/cm3) from patients with CML were less sensitive than normal targets to inhibition with low concentrations of CIA from normal PMN. However, high concentrations of CIA were as active against CML as against normal targets. The reasons for the decreased sensitivity of CML targets are discussed. These negative feedback abnormalities in vitro may partially explain granulocytic hyperplasia associated with CML.

Original languageEnglish (US)
Pages (from-to)3-12
Number of pages10
JournalLeukemia Research
Volume1
Issue number1
DOIs
StatePublished - 1977
Externally publishedYes

Keywords

  • Leukemia
  • defective inhibition
  • granulocytes
  • stem cells

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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