In vivo effects of granulocyte-macrophage colony-stimulating factor and interleukin-3 on clonal and non-clonal cell populations in patients with clonal hematopoietic disorders.
Restriction fragment length polymorphisms (RFLP) of the X-chromosome genes phosphoglycerate kinase and hypoxanthine phosphoribosyl transferase were used in conjunction with cytogenetic analysis to study the clonality of hematopoiesis in four female patients with myelodysplastic syndromes, treated with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and in one patient with essential thrombocythemia (ET) treated with IL-3. Both conventional karyotyping and X-inactivation analysis demonstrated the persistence of a monoclonal pattern of hematopoiesis in the two patients with refractory anemia (RA) treated either with GM-CSF or with IL-3. The partial restoration of non-clonal hematopoiesis was observed in one patient with RA and an excess of blasts following treatment with a combination of GM-CSF and low dose cytosine arabinoside. In a fourth patient with RA and in the patient with ET, treatment with IL-3 resulted in the complete restoration of a non-clonal pattern of peripheral blood cells. In contrast, the bone marrow cells remained monoclonal by Southern blot analysis in the patient with RA in whom it could be tested. Non-clonal lymphocytes appear to have been released into the peripheral blood in the two latter cases and are responsible for the non-clonal RFLP pattern. These results suggest that cytokine therapy may have diverse effects on hematopoiesis, including the release of residual normal cells into the peripheral blood.
Department of Hematology, University of Frankfurt, Germany.
A
A
Ganser
J W
JW
Janssen
O G
OG
Ottmann
G
G
Seipelt
M
M
Eder
R
R
Becher
A
A
Lindermann
F
F
Herrmann
G
G
Schulz
R
R
Mertelsmann
D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D008040:Genetic Linkage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006410:Hematopoiesis; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007377:Interleukin-3 / Q000627:therapeutic use*; D007962:Leukocytes / Q000473:pathology; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010735:Phosphoglycerate Kinase / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D013920:Thrombocythemia, Essential / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014960:X Chromosome
D007377:Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007041:Hypoxanthine Phosphoribosyltransferase; D010735:Phosphoglycerate Kinase