c-kit ligand augments granulocyte-macrophage colony growth from patients with 5q- syndrome.
In vitro studies may serve as a guide to clinical strategies with cytokines. In this study, marrows from 26 patients with myelodysplastic syndrome (MDS) were assayed for myeloid progenitor cells in agar gel. Colony stimulating activity was provided by the recombinant human colony stimulating factors granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), interleukin 3 (IL-3), fusion protein (FP), c-kit ligand (KL) or GM-CSF combined with other cytokines (KL, IL-3). Decreased colony forming units granulocyte-macrophage (CFU-GM) were detected in most cases (69%) compared with normal controls. Neither FP nor the combination of GM-CSF + IL-3 produced more colonies than GM-CSF alone. The number of CFU-GM did not correlate with French American British (FAB) class. All marrows (7) from patients with 5q- showed augmentation of GM-CSF induced colonies with the addition of KL. In contrast, KL augmentation was noted in only 42% of other MDS marrows (p = 0.01). This in vitro result suggests that 5q- may predict a group of MDS patients with a likelihood to respond to the combination of GM-CSF + KL.
Rosenfeld
C S
CS
West Penn Hospital, Western Pennsylvania Cancer Institute, Pittsburgh 15224.
Nemunaitis
J
J
Sherer
C R
CR
Zeigler
Z R
ZR
Shadduck
R K
RK
D002478:Cells, Cultured; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000648:ultrastructure*; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000473:pathology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; C078524:PIXY321 fusion protein, recombinant; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor