Abstract
The pathogenesis of bone marrow failure in Fanconi anemia is poorly understood. Suggested mechanisms include enhanced apoptosis secondary to DNA damage and altered inhibitory cytokine signaling. Recent data determined that disrupted cell cycle control of hematopoietic stem and/or progenitor cells disrupts normal hematopoiesis with increased hematopoietic stem cell cycling resulting in diminished function and increased sensitivity to cell cycle-specific apoptotic stimuli. Here, we used Fanconi anemia complementation type C-deficient (Fancc-/-) mice to demonstrate that Fancc -/- phenotypically defined cell populations enriched for hematopoietic stem and progenitor cells exhibit increased cycling. In addition, we established that the defect in cell cycle regulation is not a compensatory mechanism from enhanced apoptosis occurring in vivo. Collectively, these data provide a previously unrecognized phenotype in Fancc-/- hematopoietic stem/progenitor cells, which may contribute to the progressive bone marrow failure in Fanconi anemia.
| Original language | English |
|---|---|
| Pages (from-to) | 2081-2084 |
| Number of pages | 4 |
| Journal | Blood |
| Volume | 102 |
| Issue number | 6 |
| DOIs | |
| State | Published - Sep 15 2003 |
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ASJC Scopus subject areas
- Hematology
Cite this
Fanconi anemia type C-deficient hematopoietic stem/progenitor cells exhibit aberrant cell cycle control. / Li, Xiaxin; Plett, P. Artur; Yang, Yanzhu; Hong, Ping; Freie, Brian; Srour, Edward; Orschell, Christie; Clapp, D.; Haneline, Laura.
In: Blood, Vol. 102, No. 6, 15.09.2003, p. 2081-2084.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Fanconi anemia type C-deficient hematopoietic stem/progenitor cells exhibit aberrant cell cycle control
AU - Li, Xiaxin
AU - Plett, P. Artur
AU - Yang, Yanzhu
AU - Hong, Ping
AU - Freie, Brian
AU - Srour, Edward
AU - Orschell, Christie
AU - Clapp, D.
AU - Haneline, Laura
PY - 2003/9/15
Y1 - 2003/9/15
N2 - The pathogenesis of bone marrow failure in Fanconi anemia is poorly understood. Suggested mechanisms include enhanced apoptosis secondary to DNA damage and altered inhibitory cytokine signaling. Recent data determined that disrupted cell cycle control of hematopoietic stem and/or progenitor cells disrupts normal hematopoiesis with increased hematopoietic stem cell cycling resulting in diminished function and increased sensitivity to cell cycle-specific apoptotic stimuli. Here, we used Fanconi anemia complementation type C-deficient (Fancc-/-) mice to demonstrate that Fancc -/- phenotypically defined cell populations enriched for hematopoietic stem and progenitor cells exhibit increased cycling. In addition, we established that the defect in cell cycle regulation is not a compensatory mechanism from enhanced apoptosis occurring in vivo. Collectively, these data provide a previously unrecognized phenotype in Fancc-/- hematopoietic stem/progenitor cells, which may contribute to the progressive bone marrow failure in Fanconi anemia.
AB - The pathogenesis of bone marrow failure in Fanconi anemia is poorly understood. Suggested mechanisms include enhanced apoptosis secondary to DNA damage and altered inhibitory cytokine signaling. Recent data determined that disrupted cell cycle control of hematopoietic stem and/or progenitor cells disrupts normal hematopoiesis with increased hematopoietic stem cell cycling resulting in diminished function and increased sensitivity to cell cycle-specific apoptotic stimuli. Here, we used Fanconi anemia complementation type C-deficient (Fancc-/-) mice to demonstrate that Fancc -/- phenotypically defined cell populations enriched for hematopoietic stem and progenitor cells exhibit increased cycling. In addition, we established that the defect in cell cycle regulation is not a compensatory mechanism from enhanced apoptosis occurring in vivo. Collectively, these data provide a previously unrecognized phenotype in Fancc-/- hematopoietic stem/progenitor cells, which may contribute to the progressive bone marrow failure in Fanconi anemia.
UR - http://www.scopus.com/inward/record.url?scp=0141790934&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0141790934&partnerID=8YFLogxK
U2 - 10.1182/blood-2003-02-0536
DO - 10.1182/blood-2003-02-0536
M3 - Article
C2 - 12763929
AN - SCOPUS:0141790934
VL - 102
SP - 2081
EP - 2084
JO - Blood
JF - Blood
SN - 0006-4971
IS - 6
ER -