The differentiation and maturation mediator for human myeloid leukemia cells shares homology with neuroleukin or phosphoglucose isomerase.
The identity of the maturation inducer capable of mediating the differentiation of human myeloid leukemic HL-60 calls to terminal monocytic cells was investigated. One of such inducers from T cells was purified as a 54.3-kD peptide. The amino acid sequence of a tryptic peptide and the enzyme cleavage sites revealed 100% homology to neuroleukin or phosphoglucose isomerase (PGI). Neuroleukin mediates differentiation of neurons and is homologous to PGI, which catalyzes the interconversion of glucose-6-phosphate and fructose-6-phosphate. The 54.3-kD inducer was shown to have PGI enzymatic activity. Separately purified PGI by substrate-elution exhibited identical specificity as the maturation inducer for HL-60 cell differentiation. They mediated a reduction of proliferating S and G2M cells, and the mature monocytic calls acquired complement receptors, phagocytic capacity, and adherence morphology. The magnitude of differentiation was dosage dependent on the inducer, with a bell-shaped curve. At the excess dose range cells did not undergo differentiation and remained in a proliferating cycle. Abnormally elevated PGI enzyme activities were detected in the plasma of acute myelogenous leukemia patients. Whether they represent an excess of the differentiation regulator in patients and are important in leukemogenesis remain to be investigated.
Xu
W
W
Department of Medicine, New York Medical College, Valhalla 10595, USA.
Seiter
K
K
Feldman
E
E
Ahmed
T
T
Chiao
J W
JW
D000368:Aged; D000595:Amino Acid Sequence; D001685:Biological Factors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D005956:Glucose-6-Phosphate Isomerase / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology; D018922:HL-60 Cells / Q000187:drug effects*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology; D007948:Leukemia, Monocytic, Acute / Q000201:enzymology; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000097:blood; D010835:Phytohemagglutinins / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000737:chemistry*
D001685:Biological Factors; D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D009363:Neoplasm Proteins; D010835:Phytohemagglutinins; D005956:Glucose-6-Phosphate Isomerase