Cellular characteristics of acute myeloblastic leukemia associated with t(8;21)(q22;q22). The Japanese Cooperative Group of Leukemia/Lymphoma.
A large number of AML cases is reviewed in order to clarify biological characteristics of t(8;21) AML cells. The incidence of positivities for stem cell antigens, CD34 and HLA-DR, on blasts in t(8;21) AML is higher in comparison with those in other M2 or M3 categories. Frequent expression of CD34 and HLA-DR is indicative of the stem cell derivation of t(8;21) AML cells. The non-blastic leukemic cells in t(8;21) AML tend to lose the immature phenotype with discordant maturation such as low CD33 expression. Further, the blasts show frequent expression of the B-cell antigen, CD19, without other B-cell antigens and immunoglobulin gene rearrangements. AML cells with t(8;21) showed poorer response to granulocyte-macrophage colony-stimulating factor (GM-CSF) due to a decreased number of GM-CSF binding sites. The absence of monocytic differentiation in t(8;21) AML cells might represent the abnormal response to growth factors at the bifurcation stage of granulocyte and monocyte differentiation. Recently, breakpoint region genes for the 8;21 translocation in chromosome 8 and 21 have been isolated, 48-50 and have been named AML1 and ETO, respectively. The AML1 gene showed a strong homology with the Drosophila segmentation gene, runt, which is thought to be necessary for the Sex lethal gene expression. Since the GM-CSF receptor alpha chain gene locates in the pseudoautosomal region of the sex chromosome, the decrease of GM-CSF binding sites might be related to the AML1/ETO fusion gene expression. Further molecular genetic investigations of the breakpoint genes in the future are expected to clarify the unique biological events seen in this type of leukemia.
Kita
K
K
Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
Shirakawa
S
S
Kamada
N
N
D000208:Acute Disease; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002891:Chromosomes, Human, Pair 21 / Q000648:ultrastructure*; D002898:Chromosomes, Human, Pair 8 / Q000648:ultrastructure*; D005796:Genes; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007951:Leukemia, Myeloid / Q000145:classification / Q000235:genetics / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology; D010641:Phenotype; D014178:Translocation, Genetic
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D006133:Growth Substances; D009363:Neoplasm Proteins