Multiple Inhibitory Cytokines Induce Deregulated Progenitor Growth and Apoptosis in Hematopoietic Cells from Fac -/- Mice • 765

Haneline, Laura S.; Broxmeyer, Hal E.; Cooper, Scott; Hangoc, Giao; Carreau, Madeleine; Buchwald, M.; Clapp, D. Wade

doi:10.1203/00006450-199804001-00786

Cited by 78 publications

(163 citation statements)

References 0 publications

Supporting

Mentioning

155

Contrasting

Order By: Relevance

“…The increased tendency of bone marrow cells to undergo apoptosis has been demonstrated in Fanconi anemia. [11][12][13][14] It has been suggested that the normal Fanconi anemia C gene product serves, in part, to modulate interferon-␥ signals, possibly by shortening the kinetics of Stat-1-phosphate decay. 12 Hematopoietic progenitors bearing Fanconi anemia C mutations fail to modulate interferon-␥ signals normally and, as a result, undergo apoptosis executed through the Fas pathway.…”

Section: Discussionmentioning

confidence: 99%

“…9 Furthermore, preliminary studies suggested that in some patients with 3 other inherited bone marrow failure syndromes-Diamond-Blackfan anemia, 10 Fanconi anemia, [11][12][13][14] and myelokathexis 15 -apoptosis plays a role in pathogenesis. In addition, programmed cell death is central in the pathogenesis of MDS, to which patients with SDS are predisposed.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Shwachman-Diamond syndrome marrow cells show abnormally increased apoptosis mediated through the Fas pathway

Dror

Freedman

2001

Blood

110

View full text Add to dashboard Cite

Shwachman-Diamond syndrome (SDS) is an inherited bone marrow disorder with varying cytopenias and a strong predilection to myelodysplastic syndrome (MDS) and acute myeloid leukemia. Previously, it was found that the percentage of CD34 ؉ cells in bone marrow and the in vitro colony formation from CD34 ؉ cells of patients with SDS were markedly reduced. For these reasons, and because apoptosis is central in the pathogenesis of bone marrow dysfunction in MDS, this study was initiated to delineate the role of apoptosis in the pathogenesis of the marrow failure. Eleven children with SDS were studied. Compared to normal controls, patients' marrow mononuclear cells plated in clonogenic cultures showed a significantly higher tendency to undergo apoptosis. The defect in SDS was found in patients with and without MDS. Patients showed a more prominent decrease in colony formation and increased apoptosis after preincubation with activating anti-Fas antibody. Fas expression on marrow cells from patients was significantly higher than from normal controls. The difference between patients and controls for Fas expression was also significant for the following cell fraction sub-

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Shwachman-Diamond syndrome marrow cells show abnormally increased apoptosis mediated through the Fas pathway

Dror

Freedman

2001

Blood

110

View full text Add to dashboard Cite

show abstract

“…Specifically, we have shown that the mice demonstrate hypersensitivity to the inhibitory effects of IFN␥ in vitro and in vivo. 9 Haneline et al has recently reported hypersensitivity to IFN␥, TNF␣ and the chemokine MIP1␣ 11 and reduced repopulating potential in FANCC stem cells, 24 a phenomenon that is quite compatible with apoptosis in stem cells or their immediate progeny.…”

Section: Fa and The Apoptotic Phenotypementioning

confidence: 99%

“…Colony-forming units (CFU) from bone marrow of children with the C complementation group (FA-C) and knockout mice with disruptions of the group C gene (FANCC) are hypersensitive to interferon gamma (IFN␥) and tumor necrosis factor alpha (TNF␣). [9][10][11] Here, we propose a model for the evolution of neoplastic clones in children with Fanconi anemia. We also argue that MDS in FA patients is a de facto model of secondary MDS in non-FA adults (Table 1).…”

Section: Selectionmentioning

confidence: 99%

Selective pressure as an essential force in molecular evolution of myeloid leukemic clones: a view from the window of Fanconi anemia

Lensch¹,

Rathbun

Olson

et al. 1999

Leukemia

View full text Add to dashboard Cite

“…Like Bax, FANCC is localized predominantly to the cytoplasm and this localization may be crucial for its function. 52,53 Furthermore, similar to overexpression of Bax, loss of function of FANCC leads to increased apoptosis in hematopoietic cells [54][55][56] and germ cells. Therefore, both Fanconi Anemia and our Lck-Bax model are associated with increased apoptosis and CIN.…”

Section: Discussionmentioning

confidence: 99%

An expression of interest

Bonetta¹

2006

Nature

View full text Add to dashboard Cite

Bax is a Bcl-2 family member that promotes apoptosis but has paradoxical effects on lymphoma development in p53-deficient mice. To better understand the mechanism of Baxinduced lymphoma development, the effect of Bax levels, p53 status and Bcl-2 coexpression on lymphoma development were determined. In addition, DNA content and cytogenetics were performed on young (premalignant) Lck-Bax mice as measures of genetic instability. Bax promoted lymphoma development in p53-deficient mice in a dose-dependent manner. Bax expression also led to lymphoma development in both p53 +/À and +/+ animals. Ploidy analysis in mice prior to the onset of overt thymic lymphomas demonstrated that Lck-Bax transgenic mice were more likely to be aneuploid and demonstrate increased chromosome instability. With tumor progression, aneuploidy increased and Bax expression was maintained. Importantly, coexpression of Bcl-2 delayed lymphoma development in Lck-Bax transgenic mice. These data support a model in which increased sensitivity to apoptosis leads directly to chromosome instability in developing T cells and may explain a number of paradoxical observations regarding Bcl-2 family members and the regulation of cancer.

show abstract

Multiple Inhibitory Cytokines Induce Deregulated Progenitor Growth and Apoptosis in Hematopoietic Cells from Fac -/- Mice • 765

Cited by 78 publications

References 0 publications

Shwachman-Diamond syndrome marrow cells show abnormally increased apoptosis mediated through the Fas pathway

Shwachman-Diamond syndrome marrow cells show abnormally increased apoptosis mediated through the Fas pathway

Selective pressure as an essential force in molecular evolution of myeloid leukemic clones: a view from the window of Fanconi anemia

An expression of interest

Contact Info

Product

Resources

About