Macrophage lineage switching of murine early pre-B lymphoid cells expressing transduced fms genes.

Borzillo, Gary; Ashmun, RA; Sherr, Charles J.

doi:10.1128/mcb.10.6.2703

Cited by 113 publications

(54 citation statements)

References 69 publications

(60 reference statements)

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“…Third, the tyrosine kinase receptor for CSF1 (CSF1R) is expressed in ALCL cells at an unusual high level. At such a high expression level, CSF1R autophosphorylation might support malignant transformation and dedifferentiation (17,18,32). Together, these data strongly suggest that the up-regulation of breakpoint-proximal genes is a key event in ALCL biology, independent of the translocation t(2;5).…”

Section: Discussionmentioning

confidence: 60%

Gene deregulation and spatial genome reorganization near breakpoints prior to formation of translocations in anaplastic large cell lymphoma

Mathas

Kreher

Meaburn

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

101

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Although the identification and characterization of translocations have rapidly increased, little is known about the mechanisms of how translocations occur in vivo. We used anaplastic large cell lymphoma (ALCL) with and without the characteristic t(2;5)(p23;q35) translocation to study the mechanisms of formation of translocations and of ALCL transformation. We report deregulation of several genes located near the ALCL translocation breakpoint, regardless of whether the tumor contains the t(2;5). The affected genes include the oncogenic transcription factor Fra2 (located on 2p23), the HLH protein Id2 (2p25), and the oncogenic tyrosine kinase CSF1-receptor (5q33.1). Their up-regulation promotes cell survival and repression of T cellspecific gene expression programs that are characteristic for ALCL. The deregulated genes are in spatial proximity within the nuclear space of t(2;5)-negative ALCL cells, facilitating their translocation on induction of double-strand breaks. These data suggest that deregulation of breakpoint-proximal genes occurs before the formation of translocations, and that aberrant transcriptional activity of genomic regions is linked to their propensity to undergo chromosomal translocations. Also, our data demonstrate that deregulation of breakpoint-proximal genes has a key role in ALCL.cancer genetics ͉ signal transduction ͉ nuclear architecture ͉ lymphomatoid papulosis B alanced chromosomal translocations are a hallmark of cancer cells, and are thought to be important, if not causal, for hematopoietic and mesenchymal tumorigenesis (1). At the molecular level, translocations generally result in either altered expression of genes located directly at a breakpoint, or in fusion of genes located at the 2 breakpoints (1). In most cases, the affected genes are transcription factors or tyrosine kinases, and the translocation generally leads to their inactivation or constitutive activation. This defect often causes inhibition of differentiation or uncontrolled proliferation. Nevertheless, translocations are, at least in some cases, not sufficient to fully transform cells, because chromosomal disease-associated translocations are present in healthy individuals (2), and transgenic mice expressing known tumor fusion proteins do not spontaneously develop tumors in most cases (1, 2).The translocation t(2;5)(p23;q35) is characteristic for anaplastic large cell lymphoma (ALCL), a subgroup of peripheral T cell lymphomas (TCL) (3, 4). By fusion of the 5Ј oligomerization domain of the nucleophosmin (NPM1) gene (located on 5q35) with the 3Ј anaplastic lymphoma kinase (ALK) tyrosine kinase domain (2p23), this translocation results in a NPM-ALK fusion protein with constitutive activation of the ALK kinase (3). Several questions regarding the pathogenesis of ALCL are unresolved. First, in Ϸ40% of systemic ALCL, the translocation t(2;5) is not present (4), suggesting yet unknown alternative mechanisms of transformation. Second, the expression of NPM-ALK per se might not be sufficient for malignant transformation to ALC...

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Section: Discussionmentioning

confidence: 60%

Gene deregulation and spatial genome reorganization near breakpoints prior to formation of translocations in anaplastic large cell lymphoma

Mathas

Kreher

Meaburn

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

101

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“…Thus, about 5-10% of acute leukemias in adult humans display characteristics of both pre-B and myeloid lineages. 24 Furthermore, a number of studies using immortalized lymphoid cell lines [25][26][27][28][29] or transgenic mice 11,30 have indicated in transformed cells a repeated pattern of bipotentiality, often linking B-lymphoid and macrophage lineages. The PGM-1 cell line with B-lymphoid markers and an ability to form granulocyte-macrophage colonies in agar is a further example of this bipotentiality.…”

Section: Discussionmentioning

confidence: 99%

Differentiation commitment and regulator-specific granulocyte–macrophage maturation in a novel pro-B murine leukemic cell line

et al. 2000

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The cloned pro-B-lymphocyte murine leukemic cell line GB2, was established from a leukemic Max41 x E -myc double transgenic mouse. Its Igh alleles are rearranged and its surface markers are primarily B-lymphoid, but a small proportion of the cells also express surface Gr-1 and some cells develop the morphology of maturing granulocytes. The cell line grows continuously in suspension culture without the addition of growth factors, but expresses mRNA for M-CSF, TPO and Flt-3-ligand. When stimulated in agar cultures by GM-CSF, G-CSF, M-CSF, IL-3, SCF, IL-6, leukemia inhibitory factor (LIF), IL-5 or IFN␥, GB2 cells generated blast colonies or colonies of maturing granulocytes and macrophages. There was a striking similarity in colony types, relative colony numbers and maturation of colony cells to those formed by normal bone marrow cells in response to the same stimuli. GB2 blast colony-forming cells exhibited self-renewal as well as an ability to form granulocytemacrophage colony-forming progeny, with evidence that a hierarchical sequence of clonogenic cells is generated in the cell line even after subcloning. Factor-specific maturation was clearly initiated by the action of the added growth factors. In contrast, FACS-sorting experiments showed that commitment to various types of colony-forming cell occurs in maintenance suspension cultures in the apparent absence of potentially relevant growth factors. Leukemia (2000) 14, 1785-1795.

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“…B-lineage cells have been also shown to transit into neutrophils or natural killer (NK)/T-lineage cells. [4][5][6][7][8] Furthermore, the macrophage cell line differentiates into B-lineage cells. 9 Common lymphoid progenitors that exogenously express cytokine receptors or transcriptional factors develop myeloid lineage cells.…”

Section: Introductionmentioning

confidence: 99%

Reprogramming of human postmitotic neutrophils into macrophages by growth factors

Araki

Katayama

Yamashita

et al. 2004

Blood

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It is generally recognized that postmitotic neutrophils give rise to polymorphonuclear neutrophils alone. We obtained evidence for a lineage switch of human postmitotic neutrophils into macrophages in culture. When the CD15 ؉ CD14 ؊ cell population, which predominantly consists of band neutrophils, was cultured with granulocyte macrophage-colonystimulating factor, tumor necrosis factor-␣, interferon-␥, and interleukin-4, and subsequently with macrophage colonystimulating factor alone, the resultant cells had morphologic, cytochemical, and phenotypic features of macrophages. In contrast to the starting population, they were negative for myeloperoxidase, specific esterase, and lactoferrin, and they upregulated nonspecific esterase activity and the expression of macrophage colony-stimulating factor receptor, mannose receptor, and HLA-DR. CD15 ؉ CD14 ؊ cells proceeded to macrophages through the CD15 ؊ CD14 ؊ cell population. Microarray analysis of gene expression also disclosed the lineage conversion from neutrophils to macrophages. Macrophages derived from CD15 ؉ CD14 ؊ neutrophils had phagocytic function. Data obtained using 3 different techniques, including Ki-67 staining, bromodeoxyuridine incorporation, and cytoplasmic dye labeling, together with the yield of cells, indicated that the generation of macrophages from CD15 ؉ CD14 ؊ neutrophils did not result from a contamination of progenitors for macrophages. Our data show that in response to cytokines, postmitotic neutrophils can become macrophages. This may represent another differentiation pathway toward macrophages in human postnatal

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Macrophage lineage switching of murine early pre-B lymphoid cells expressing transduced fms genes.

Cited by 113 publications

References 69 publications

Gene deregulation and spatial genome reorganization near breakpoints prior to formation of translocations in anaplastic large cell lymphoma

Gene deregulation and spatial genome reorganization near breakpoints prior to formation of translocations in anaplastic large cell lymphoma

Differentiation commitment and regulator-specific granulocyte–macrophage maturation in a novel pro-B murine leukemic cell line

Reprogramming of human postmitotic neutrophils into macrophages by growth factors

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