Defects in yolk sac hematopoiesis in Mll-null embryos

Jay L. Hess, Benjamin D. Yu, Bin Li, Rob Hanson, Stanley J. Korsmeyer

Research output: Contribution to journalArticle

214 Scopus citations

Abstract

Translocations involving the mixed lineage leukemia gene (MLL), the human homolog of the Drosophila gene trithorax, are one of the most common genetic alterations in human acute leukemias. Each translocation involving MLL results in loss of one functional copy of MLL and the generation of a chimeric fusion protein with potential dominant negative or neomorphic activity. MII is a positive regulator of Hox genes, which have been implicated in both axial skeleton patterning and hematopoietic development. Previous studies indicated that Hox gene expression is altered in MII heterozygous (+/-) and homozygous (-/-) deficient mice. To study the role of MII in hematopoiesis and to obtain insights into leukemogenesis, we have examined the effects of haplo-insufficiency or absence of MII by in vitro differentiation of MII +/+, +/-, and -/- yolk sac progenitor cells. MII -/- colonies were fewer in number, took longer to develop, and contained fewer cells than their wild-type and heterozygous counterparts. Formation of colony-forming unit-granulocyte, erythroid, macrophage, megakaryocyte (CFU- GEMM), colony-forming unit-macrophage (CFU-M), and burst-forming unit- erythroid (BFU-E) was markedly decreased in MII -/- cultures, while numbers of colony-forming unit-erythroid (CFU-E), colony-forming unit-granulocyte (CFU-G), and colony-forming unit-granulocyte macrophage (CFU-GM) were essentially unaffected. Despite the decreased numbers of colonies present, MII -/- cultures showed all cell types without morphologic evidence of maturation arrest. These studies indicate that MII is required for normal numbers of hematopoietic progenitors and their proper differentiation, especially along the myeloid and macrophage pathways.

Original languageEnglish (US)
Pages (from-to)1799-1806
Number of pages8
JournalBlood
Volume90
Issue number5
DOIs
StatePublished - Sep 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Hess, J. L., Yu, B. D., Li, B., Hanson, R., & Korsmeyer, S. J. (1997). Defects in yolk sac hematopoiesis in Mll-null embryos. Blood, 90(5), 1799-1806. https://doi.org/10.1182/blood.v90.5.1799