Defects in yolk sac hematopoiesis in Mll-null embryos

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

Research output: Contribution to journalArticle

212 Citations (Scopus)

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
StatePublished - Sep 1 1997
Externally publishedYes

Fingerprint

Yolk Sac
Hematopoiesis
Macrophages
Leukemia
Embryonic Structures
Genes
Defects
Erythroid Precursor Cells
Stem Cells
Homeobox Genes
Myeloid Progenitor Cells
Granulocyte-Macrophage Progenitor Cells
Regulator Genes
Granulocytes
Skeleton
Drosophila
Gene expression
Gene Expression
Fusion reactions
Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

Hess, J., 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.

Defects in yolk sac hematopoiesis in Mll-null embryos. / Hess, Jay; Yu, Benjamin D.; Li, Bin; Hanson, Rob; Korsmeyer, Stanley J.

In: Blood, Vol. 90, No. 5, 01.09.1997, p. 1799-1806.

Research output: Contribution to journalArticle

Hess, J, Yu, BD, Li, B, Hanson, R & Korsmeyer, SJ 1997, 'Defects in yolk sac hematopoiesis in Mll-null embryos', Blood, vol. 90, no. 5, pp. 1799-1806.
Hess J, Yu BD, Li B, Hanson R, Korsmeyer SJ. Defects in yolk sac hematopoiesis in Mll-null embryos. Blood. 1997 Sep 1;90(5):1799-1806.
Hess, Jay ; Yu, Benjamin D. ; Li, Bin ; Hanson, Rob ; Korsmeyer, Stanley J. / Defects in yolk sac hematopoiesis in Mll-null embryos. In: Blood. 1997 ; Vol. 90, No. 5. pp. 1799-1806.
@article{e0f2e4a13b544484872ba195bafa6ad7,
title = "Defects in yolk sac hematopoiesis in Mll-null embryos",
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.",
author = "Jay Hess and Yu, {Benjamin D.} and Bin Li and Rob Hanson and Korsmeyer, {Stanley J.}",
year = "1997",
month = "9",
day = "1",
language = "English (US)",
volume = "90",
pages = "1799--1806",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "5",

}

TY - JOUR

T1 - Defects in yolk sac hematopoiesis in Mll-null embryos

AU - Hess, Jay

AU - Yu, Benjamin D.

AU - Li, Bin

AU - Hanson, Rob

AU - Korsmeyer, Stanley J.

PY - 1997/9/1

Y1 - 1997/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0030954681&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030954681&partnerID=8YFLogxK

M3 - Article

C2 - 9292512

AN - SCOPUS:0030954681

VL - 90

SP - 1799

EP - 1806

JO - Blood

JF - Blood

SN - 0006-4971

IS - 5

ER -