Blasts in transient leukaemia in neonates with Down syndrome differentiate into basophil/mast-cell and megakaryocyte lineages in vitro in association with down-regulation of truncated form of GATA1.
Mutations of GATA1, leading to aberrant expression of a truncated form of GATA1 (called GATA1s), are present in transient leukaemia (TL) in neonates with Down syndrome. Using these molecular markers of TL, we investigated the growth and differentiation potential of TL blasts in the presence of hematopoietic growth factors (HGFs). Interleukin-3, stem cell factor and granulocyte-macrophage colony-stimulating factor potently stimulated the growth of TL blast progenitors and induced differentiation towards basophil/mast cell lineages, whereas thrombopoietin induced differentiation towards megakaryocytes. GATA1s was expressed in TL blasts in all five patients examined but was down-regulated during differentiation induced by these HGFs, while full-length GATA1 was not expressed throughout the culture. GATA1 mutations were detected in TL blasts in four patients, including one patient with two distinct mutations. The cells of this patient exhibited identical and only mutated sequences both before and after culture with HGFs, confirming the leukemic cell origin of these differentiated cells. Erythroid differentiation of TL blasts was not evident with any HGFs. These data indicate that TL blasts have the potential to grow and differentiate towards particular hematopoietic lineages in the presence of specific HGFs and that the down-regulation of GATA1s might be involved in blast cell differentiation.
Miyauchi
Jun
J
Department of Pathology and Laboratory Medicine, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba-ken, Japan. jmiyauchi@tdc.ac.jp
Ito
Yushi
Y
Tsukamoto
Keiko
K
Takahashi
Hirotaka
H
Ishikura
Kenji
K
Sugita
Kiyoko
K
Miyashita
Toshiyuki
T
D001491:Basophils / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D004314:Down Syndrome / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D007947:Leukemia, Megakaryoblastic, Acute / Q000235:genetics / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000473:pathology; D008533:Megakaryocytes / Q000473:pathology; D008854:Microscopy, Electron; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*
D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D006133:Growth Substances; D009363:Neoplasm Proteins