Modulation of homeobox gene expression alters the phenotype of human hematopoietic cell lines.

We have previously reported that certain members of the HOX 1 and HOX 2 clusters of class 1 homeobox-containing genes showed lineage-restricted patterns of expression in a small series of human hematopoietic cell lines. We now report on the expression patterns of the entire HOX 2 cluster, consisting of nine homeobox genes, in a broad survey of leukemic cell lines of different phenotypes. The most striking observation is that all but one of the HOX 2 genes are consistently expressed in cells with erythroid character and/or potential, but, with rare exception, not in cells with myelomonocytic or T- or B-lymphoid phenotype. By contrast, several genes of the HOX 1 and 3 loci are not expressed in erythroid lines. Within erythroid cell lines, many of the HOX 2 genes are expressed as multiple transcripts. Expression of some HOX 2 genes is detectable in normal human marrow. These data show that in human hematopoietic cell lines HOX 2 homeobox gene expression is largely restricted to cells of erythroid phenotype and suggest that these genes play a role in erythropoiesis.

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Gene Expression Profiling of Leukemic Cell Lines and Primary Leukemias Reveals Conserved Molecular Signatures among Subtypes with Specific Genetic Aberrations: Identification of Fusion Gene-Specific Transcriptional Profiles and Expression Pattern of Tyrosine Kinase-Encoding Genes.

Blood ◽

10.1182/blood.v104.11.2044.2044 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2044-2044

Author(s):

Anna Andersson ◽

Patrik Edén ◽

David Lindgren ◽

Jens Nilsson ◽

Carin Lassen ◽

...

Keyword(s):

Gene Expression ◽

Tyrosine Kinase ◽

Cell Lines ◽

Regulatory Networks ◽

Expression Profiles ◽

Hematopoietic Cell ◽

Genetic Changes ◽

Regulatory Pathways ◽

Encoding Genes ◽

Hematopoietic Cell Lines

Abstract Hematologic malignancies are characterized by fusion genes of biological/clinical importance. Immortalized cell lines with such aberrations are today widely used to model different aspects of leukemogenesis. Using cDNA microarrays, we determined the gene expression profiles of 40 cell lines as well as of primary leukemias harboring 11q23/MLL-rearrangements, t(1;19)[TCF3/PBX1], t(12;21)[ETV6/RUNX1], t(8;21)[RUNX1/CBFA2T1], t(8;14)[IGH@/MYC], t(8;14)[TRA@/MYC], t(9;22)[BCR/ABL1], t(10;11)[PICALM/MLLT10], t(15;17)[PML/RARA], or inv(16)[CBFB/MYH11]. Unsupervised classification revealed that hematopoietic cell lines of diverse origin, but with the same primary genetic changes, segregated together, suggesting that pathogenetically important regulatory networks remain conserved despite numerous passages. Moreover, primary leukemias co-segregated with cell lines carrying identical genetic rearrangements, further supporting that critical regulatory pathways remain intact in hematopoietic cell lines. Transcriptional signatures correlating with clinical subtypes/primary genetic changes were identified and annotated based on their biological/molecular properties and chromosomal localization. Furthermore, the expression profile of tyrosine kinase-encoding genes was investigated, identifying several differentially expressed members, segregating with primary genetic changes, which may be targeted with tyrosine kinase inhibitors. The identified conserved signatures are likely to reflect regulatory networks of importance for the transforming abilities of the primary genetic changes and offer important pathogenetic insights as well as a number of targets for future rational drug design.

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Erythroid-restricted expression of homeobox genes of the human HOX 2 locus

Blood ◽

10.1182/blood.v78.9.2248.2248 ◽

1991 ◽

Vol 78 (9) ◽

pp. 2248-2252 ◽

Cited By ~ 28

Author(s):

CH Mathews ◽

K Detmer ◽

E Boncinelli ◽

HJ Lawrence ◽

C Largman

Keyword(s):

Cell Lines ◽

Expression Patterns ◽

Homeobox Genes ◽

Homeobox Gene ◽

Leukemic Cell ◽

Hematopoietic Cell ◽

Erythroid Cell ◽

Small Series ◽

Hematopoietic Cell Lines ◽

In Cells

Abstract We have previously reported that certain members of the HOX 1 and HOX 2 clusters of class 1 homeobox-containing genes showed lineage-restricted patterns of expression in a small series of human hematopoietic cell lines. We now report on the expression patterns of the entire HOX 2 cluster, consisting of nine homeobox genes, in a broad survey of leukemic cell lines of different phenotypes. The most striking observation is that all but one of the HOX 2 genes are consistently expressed in cells with erythroid character and/or potential, but, with rare exception, not in cells with myelomonocytic or T- or B-lymphoid phenotype. By contrast, several genes of the HOX 1 and 3 loci are not expressed in erythroid lines. Within erythroid cell lines, many of the HOX 2 genes are expressed as multiple transcripts. Expression of some HOX 2 genes is detectable in normal human marrow. These data show that in human hematopoietic cell lines HOX 2 homeobox gene expression is largely restricted to cells of erythroid phenotype and suggest that these genes play a role in erythropoiesis.

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Malignant hematopoietic cell lines: In vitro models for the study of primary mediastinal B-cell lymphomas

Leukemia Research ◽

10.1016/j.leukres.2014.11.002 ◽

2015 ◽

Vol 39 (1) ◽

pp. 18-29 ◽

Cited By ~ 8

Author(s):

Hans G. Drexler ◽

Stefan Ehrentraut ◽

Stefan Nagel ◽

Sonja Eberth ◽

Roderick A.F. MacLeod

Keyword(s):

B Cell ◽

Cell Lines ◽

In Vitro Models ◽

Hematopoietic Cell ◽

B Cell Lymphomas ◽

Hematopoietic Cell Lines

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Regulation of pim and myb mRNA accumulation by interleukin 2 and interleukin 3 in murine hematopoietic cell lines.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)77880-6 ◽

1988 ◽

Vol 263 (33) ◽

pp. 17615-17620

Author(s):

F Dautry ◽

D Weil ◽

J Yu ◽

A Dautry-Varsat

Keyword(s):

Cell Lines ◽

Interleukin 2 ◽

Hematopoietic Cell ◽

Mrna Accumulation ◽

Interleukin 3 ◽

Hematopoietic Cell Lines

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Collagen type VI in the human bone marrow microenvironment: a strong cytoadhesive component

Blood ◽

10.1182/blood.v86.5.1740.bloodjournal8651740 ◽

1995 ◽

Vol 86 (5) ◽

pp. 1740-1748 ◽

Cited By ~ 50

Author(s):

G Klein ◽

CA Muller ◽

E Tillet ◽

ML Chu ◽

R Timpl

Keyword(s):

Bone Marrow ◽

Cell Lines ◽

Triple Helix ◽

Collagen Type ◽

Hematopoietic Cell ◽

Human Bone ◽

Human Bone Marrow ◽

Collagen Vi ◽

Collagen Type Vi ◽

Hematopoietic Cell Lines

Collagen type VI, which forms characteristic microfibrillar structures, is assembled from three individual alpha(VI) chains that form a short triple helix and two adjacent globular domains. Expression of all three alpha (VI) collagen chains in the human bone marrow (BM) microenvironment could be detected by chain-specific antibodies in tissue sections and in the adherent stromal layer of long-term BM cultures. In functional studies, collagen type VI was shown to be a strong adhesive substrate for various hematopoietic cell lines and light-density BM mononuclear cells. The adhesive site within the molecule seems to be restricted to the triple helical domain of all three alpha (VI) chains, because individual alpha (VI) chains were not active in the attachment assays. Adhesion of the hematopoietic cell lines to collagen VI was dose-dependent and could be inhibited by heparin. Although the triple helix contains several RGD sequences, adhesion of the hematopoietic cell types to collagen VI could be blocked neither by RGD-containing peptides nor by a neutralizing antibody to the beta 1 integrin subunit. In combination with an antiadhesive substrate, the binding properties of collagen VI could be downregulated. These data suggest that this collagen type may play an important role in the adhesion of hematopoietic cells within the BM microenvironment.

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